39 results on '"Andersson, Borje S."'
Search Results
2. Optimizing the Conditioning Regimen for Hematopoietic Cell Transplant in Myelofibrosis: Long-Term Results of a Prospective Phase II Clinical Trial.
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Popat U, Mehta RS, Bassett R, Kongtim P, Chen J, Alousi AM, Anderlini P, Ciurea S, Hosing C, Jones R, Kebriaei P, Khouri I, Lindsay R PA, Nieto Y, Olson A, Oran B, Qazilbash MH, Rondon G, Shpall EJ, Verstovsek S, Andersson BS, and Champlin RE
- Subjects
- Aged, Busulfan, Humans, Middle Aged, Neoplasm Recurrence, Local, Prospective Studies, Transplantation Conditioning, Vidarabine therapeutic use, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute, Primary Myelofibrosis therapy
- Abstract
Optimal conditioning regimens for older patients with myelofibrosis undergoing allogeneic hematopoietic cell transplant are not known. Likewise, the role of dose intensity is not clear. We conducted a nonrandomized, prospective, phase II trial using low-dose, later escalated to high-dose (myeloablative conditioning), busulfan with fludarabine (Bu-Flu) in myelofibrosis patients up to age 74 years. The first 15 patients received i.v. busulfan 130 mg/m
2 /day on days -3 and -2 ("low dose"); 31 patients received high-dose conditioning, either 100 mg/m2 /day (days -5 to -2; n = 4) or pharmacokinetic-guided area under the curve of 4000 μmol/min (days -5 to -2; n = 27). The primary endpoint was day 100 nonrelapse mortality (NRM). Median age was 58 years (interquartile range [IQR], 53-63). Dynamic international prognostic scoring system-plus was intermediate (n = 28) or high (n = 18). Donors were related (n = 19) or unrelated (n = 27). Cumulative incidence of NRM was 9.7% (95% confidence interval [CI], 0-20.3) at day 100 and at 3 years in the high-dose group and 0% in the low-dose group at day 100, which increased to 20% (95% CI, 0-41.9) at 3 years. With a median follow-up of 5.1 years (IQR, 3.8-6), 3-year relapse was 32.3% (95% CI, 15.4-49.1) in high dose versus 53.3% (95% CI, 26.6-80.1) in low dose. Event-free survival was 58% (95% CI, 43-78) versus 27% (95% CI, 12-62), and overall survival was 74% (95% CI, 60-91) versus 60% (95% CI, 40-91). In multivariate analysis, high-dose busulfan had a trend toward lower relapse (hazard ratio, .44; 95% CI, .18-1.07; P = .07), with no impact on NRM. Intensifying the Bu-Flu regimen using pharmacokinetic-monitoring appears to be promising in reducing relapse without increasing NRM., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
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3. Hematopoietic Stem Cell Transplantation for Severe Thalassemia Patients from Haploidentical Donors Using a Novel Conditioning Regimen.
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Anurathapan U, Hongeng S, Pakakasama S, Songdej D, Sirachainan N, Pongphitcha P, Chuansumrit A, Charoenkwan P, Jetsrisuparb A, Sanpakit K, Rujkijyanont P, Meekaewkunchorn A, Lektrakul Y, Iamsirirak P, Surapolchai P, Sirireung S, Sruamsiri R, Wahidiyat PA, and Andersson BS
- Subjects
- Busulfan therapeutic use, Child, Humans, Transplantation Conditioning, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Thalassemia therapy
- Abstract
Patients with severe thalassemia commonly have a survival that is significantly shorter than that of the general population. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only established treatment that is potentially curative, but it is limited by the availability of donors and the medical condition of the patient. To expand the donor pool to include haploidentical related donors, we introduced a program consisting of a pharmacologic pretransplant immune suppression phase (PTIS) and 2 courses of dexamethasone and fludarabine, followed by pretransplant conditioning with fludarabine-i.v. busulfan and post-transplant graft-versus-host disease (GVHD) prophylaxis with cyclophosphamide, tacrolimus, and mycophenolate mofetil. We transplanted 83 consecutive transfusion-dependent patients with thalassemia (median age, 12 years; range, 1 to 28 years) with a minimum follow-up of 6 months (median, 15 months; range, 7 to 53 months); the 3-year projected overall and event-free survival is over 96%, and there have been no secondary graft failures. Of the first 31 patients, we had 2 graft failures, both of them occurring in patients with extremely high titers of anti-donor-specific HLA antibodies (anti-DSAs), but after adjusting the PTIS to include bortezomib and rituximab for patients with high titers of anti-DSAs and using pharmacologic dose guidance for busulfan, we had no graft failures in the last 52 patients. Six (7%) of 83 patients developed severe GVHD. We conclude that this is a safe and efficacious approach to allogeneic SCT in thalassemia, yielding results comparable to those available for patients with fully matched donors., (Copyright © 2020. Published by Elsevier Inc.)
- Published
- 2020
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4. Phase II Trial of High-Dose Gemcitabine/Busulfan/Melphalan with Autologous Stem Cell Transplantation for Primary Refractory or Poor-Risk Relapsed Hodgkin Lymphoma.
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Nieto Y, Thall PF, Ma J, Valdez BC, Ahmed S, Anderlini P, Popat U, Jones RB, Shpall EJ, Hosing C, Qazilbash M, Kebriaei P, Alousi A, Timmons M, Gulbis A, Myers A, Oki Y, Fanale M, Dabaja B, Pinnix C, Milgrom S, Champlin R, and Andersson BS
- Subjects
- Adult, Busulfan therapeutic use, Carmustine therapeutic use, Cytarabine therapeutic use, Deoxycytidine analogs & derivatives, Deoxycytidine therapeutic use, Etoposide therapeutic use, Hodgkin Disease mortality, Humans, Melphalan therapeutic use, Middle Aged, Salvage Therapy mortality, Survival Analysis, Transplantation, Autologous, Young Adult, Gemcitabine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation methods, Hodgkin Disease therapy, Salvage Therapy methods
- Abstract
We conducted a prospective phase 2 trial of gemcitabine, busulfan and melphalan (Gem/Bu/Mel) with autologous stem cell transplantation (ASCT) in patients with primary refractory or poor-risk relapsed Hodgkin lymphoma (HL) (ie, extranodal relapse or within 1 year of frontline therapy). The trial was powered to detect an improvement in 2-year progression-free survival (PFS) from a historical 50% using a BEAM regimen (carmustine/etoposide/cytarabine/melphalan) to 65%. We compared the study population with all other concurrent patients who were eligible for the trial but instead received the BEAM regimen at our center. No patient received post-ASCT maintenance therapy. The Gem/Bu/Mel trial enrolled 80 patients with a median age of 31 years, 41% with primary refractory HL and 59% with relapsed HL (36% extranodal relapses), and 30% with positron emission tomography (PET)-positive lesions at ASCT. The concurrent BEAM (n = 45) and Gem/Bu/Mel cohorts were well balanced except for higher rates of bulky relapse and PET-positive tumors in the Gem/Bu/Mel cohort. There were no transplantation-related deaths in either cohort. At a median follow-up of 34.5 months (range, 26 to 72 months), Gem/Bu/Mel was associated with better 2-year PFS (65% versus 51%; P = .008) and overall survival (89% versus 73%; P = .0003). In conclusion, our data show that Gem/Bu/Mel is safe, in this nonrandomized comparison yielding improved outcomes compared with a concurrently treated and prognostically matched cohort of patients with primary refractory or poor-risk relapsed HL receiving BEAM., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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5. Early Post-Transplant Minimal Residual Disease Assessment Improves Risk Stratification in Acute Myeloid Leukemia.
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Shah MV, Jorgensen JL, Saliba RM, Wang SA, Alousi AM, Andersson BS, Bashir Q, Ciurea SO, Kebriaei P, Marin D, Patel KP, Popat UR, Rezvani K, Rondon G, Shpall EJ, Champlin RE, and Oran B
- Subjects
- Adult, Aged, Female, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Neoplasm, Residual pathology, Risk Factors, Stem Cell Transplantation methods, Young Adult, Leukemia, Myeloid, Acute therapy, Neoplasm, Residual therapy, Stem Cell Transplantation adverse effects
- Abstract
We studied if the inclusion of early post-stem cell transplantation (SCT) minimal residual disease (MRD) assessments improved prognostication in patients with acute myeloid leukemia (AML). Two hundred sixty-nine AML patients in morphological complete remission (CR) who underwent a first SCT were included if they had evaluable pre-SCT MRD assessment by multiparametric flow cytometry. Post-SCT MRD assessments were performed at days +30, +100, and +180. The primary outcome was 1-year relapse incidence (RI). Of 269 patients in CR, 83 (30.8%) had detectable MRD pre-SCT. Post-SCT, during routine disease assessment time points, 9 of 241 evaluable patients (3.7%) at day +30, 6 of 191 evaluable patients (3.1%) at day +100, and 4 of 133 evaluable patients (3%) at day +180 were MRD positive while in CR. MRD positivity at day +30 predicted the highest risk of relapse at 1 year (group 1, 1-year RI 78%). Among MRD-negative patients at day +30, either adverse risk category by European Leukemia Net (ELN) or intermediate risk who were aged ≥60 years and/or pre-SCT MRD-positive represented the intermediate-risk group (group 2, 1-year RI 29%). The remaining patients represented the low-risk group (group 3, 1-year RI 5%). For patients in CR beyond day +30 post-SCT, detectable MRD at any time point predicted impending relapse within 2 months. Early post-SCT MRD assessment-combined with pre-SCT MRD assessment, ELN risk category, and age-improves risk stratification for relapse in AML patients post-transplant. Studies aimed at preventing impending relapse in this high-risk population are urgently needed., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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6. Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndrome: Comparison of Outcomes between CD34 + Selected and Unmodified Hematopoietic Stem Cell Transplantation.
- Author
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Tamari R, Oran B, Hilden P, Maloy M, Kongtim P, Papadopoulos EB, Rondon G, Jakubowski AA, Andersson BS, Devlin SM, Ahmed S, Popat UR, Ponce D, Chen J, Sauter C, Young JW, de Lima M, Perales MA, O'Reilly RJ, Giralt SA, Champlin RE, and Castro-Malaspina H
- Subjects
- Adult, Aged, Allografts cytology, Chromosome Aberrations, Female, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation mortality, Humans, Lymphocyte Depletion, Male, Middle Aged, Myelodysplastic Syndromes complications, Myelodysplastic Syndromes mortality, Recurrence, Risk Assessment, Survival Analysis, Transplantation, Homologous, Treatment Outcome, Antigens, CD34 blood, Hematopoietic Stem Cell Transplantation methods, Myelodysplastic Syndromes therapy
- Abstract
In this study, we compared transplantation outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with advanced myelodysplastic syndrome (MDS) who received a CD34
+ cell-selected and those who received an unmodified allograft. This analysis initially included 181 patients, 60 who received a CD34+ cell-selected transplant and 121 who received an unmodified transplant. Owing to significant differences in disease characteristics, the analysis was limited to patients with <10% blasts before HSCT (n = 145). Two groups were defined: low risk, with low- and intermediate-risk cytogenetics (CD34+ , n = 39; unmodified, n = 46), and high risk: poor and very poor risk cytogenetics (CD34+ , n = 19; unmodified, n = 41). In the low-risk group, the incidence of grade II-IV acute graft-versus-host disease (aGVHD) at 1 year post-transplantation was 18% in the CD34+ subgroup versus 41.3% in the unmodified subgroup (P = .015). There were no differences between the subgroups in the incidence of grade III-IV aGVHD. The incidence of chronic graft-versus-host disease (cGVHD) at 3 years in the 2 subgroups was 5.3% and 56%, respectively (P < .001). At 3 years post-transplantation, relapse, overall survival (OS), and relapse-free survival (RFS) were similar in the CD34+ and unmodified subgroups: 8.1% versus 19.4% (P = .187), 58.5% versus 53.7% (P = .51), and 59.5% versus 52.4% (P = .448). However, the composite outcome combining extensive cGVHD-free status and relapse-free status (CRFS) at 3 years was 59.5% in the CD34+ group versus 19.2% in the unmodified group (P < .001). In the high-risk group, grade II-IV aGVHD at 1 year was 31.6% in the CD34+ subgroup versus 24.4% in the unmodified subgroup (P = .752). There were no differences between the subgroups in the incidence of grade III-IV aGVHD. The incidence of cGVHD at 3 years in the 2 subgroups was 0% versus 27.6% (P = .013). At 3 years post-transplantation, relapse, OS, RFS, and CRFS in the 2 subgroups were 31.6% versus 69.3% (P = .007), 35.5% versus 14.5% (P = .068), 31.6% versus 10.7% (P = .045), and 31.6% versus 6.1% (P = .001), respectively. Cytogenetic abnormalities at diagnosis and transplant type had significant univariate associations with RFS in the high-risk cohort. Only cytogenetics (P = .03) remained associated with this outcome in a multivariate model. OS was similar in the 2 transplant groups; however, CRFS was superior in the CD34+ cell-selected transplant group., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
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7. Clofarabine Plus Busulfan is an Effective Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Lymphoblastic Leukemia: Long-Term Study Results.
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Kebriaei P, Bassett R, Lyons G, Valdez B, Ledesma C, Rondon G, Oran B, Ciurea S, Alousi A, Popat U, Patel K, Ahmed S, Olson A, Bashir Q, Shah N, Jones R, Marin D, Rezvani K, Nieto Y, Khouri I, Qazilbash M, Hosing C, Shpall E, Champlin RE, and Andersson BS
- Subjects
- Adolescent, Adult, Allografts, Clofarabine, Disease-Free Survival, Dose-Response Relationship, Drug, Female, Graft vs Host Disease etiology, Humans, Male, Middle Aged, Whole-Body Irradiation, Young Adult, Adenine Nucleotides administration & dosage, Arabinonucleosides administration & dosage, Busulfan administration & dosage, Hematopoietic Stem Cell Transplantation adverse effects, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Transplantation Conditioning methods
- Abstract
We investigated the long-term safety and disease control data obtained with i.v. busulfan (Bu) combined with clofarabine (Clo) in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). A total of 107 patients, median age 38 years (range, 19 to 64 years) received a matched sibling donor (n = 52) or matched unrelated donor (n = 55) transplant for ALL in first complete remission (n = 62), second complete remission (n = 28), or more advanced disease (n = 17). Nearly one-half of the patients had a high-risk cytogenetic profile as defined by the presence of t(9;22) (n = 34), t(4;11) (n = 4), or complex cytogenetics (n = 7). Clo 40 mg/m
2 was given once daily, with each dose followed by pharmacokinetically dosed Bu infused over 3 hours daily for 4 days, followed by hematopoietic cell infusion after 2 days of rest. The Bu dose was based on the drug clearance as determined by a test Bu dose of 32 mg/m2 . The target daily area under the curve was 5500 µmol/min for patients aged <60 years and 4000 µmol/min for patients aged >59 years. With a median follow-up of 3.3 years among surviving patients (range, 1 to 5.8 years), the 2-year progression-free survival (PFS) for patients undergoing HSCT in first complete remission (CR1), second complete remission (CR2), or more advanced disease was 62%, 34%, and 35%, respectively. The regimen was well tolerated, with nonrelapse mortality (NRM) of 10% at 100 days and 31% at 2 years post-HSCT. The incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) was 35% and 10%, respectively; 18% patients developed extensive chronic GVHD. The 2-year overall survival (OS) for patients undergoing HSCT in CR1, CR2, or more advanced disease was 70%, 57%, and 35%, respectively. Among 11 patients aged >59 years treated with reduced-dose Bu in CR1 (n = 7) or CR2 (n = 4), 4 remain alive and disease-free, with a median follow-up of 2.6 years (range, 2 to 4.7 years). Only the presence of minimal residual disease at the time of transplantation was associated with significantly worse PFS and OS in multivariate analysis. Our data indicate that the Clo-Bu combination provides effective disease control while maintaining a favorable safety profile. OS and NRM rates compare favorably with those for traditional myeloablative total body irradiation-based conditioning regimens., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)- Published
- 2017
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8. Long-Term Outcomes after Treatment with Clofarabine ± Fludarabine with Once-Daily Intravenous Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and Myelodysplastic Syndrome.
- Author
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Alatrash G, Thall PF, Valdez BC, Fox PS, Ning J, Garber HR, Janbey S, Worth LL, Popat U, Hosing C, Alousi AM, Kebriaei P, Shpall EJ, Jones RB, de Lima M, Rondon G, Chen J, Champlin RE, and Andersson BS
- Subjects
- Adolescent, Adult, Child, Clofarabine, Female, Graft Survival, Graft vs Host Disease etiology, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive complications, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myeloid, Acute complications, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Myelodysplastic Syndromes complications, Myelodysplastic Syndromes mortality, Remission Induction, Survival Analysis, Treatment Outcome, Vidarabine therapeutic use, Young Adult, Adenine Nucleotides therapeutic use, Arabinonucleosides therapeutic use, Busulfan administration & dosage, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes therapy, Transplantation Conditioning methods, Vidarabine analogs & derivatives
- Abstract
Pretransplant conditioning regimens critically determine outcomes in the setting of allogeneic stem cell transplantation (allo-SCT). The use of nucleoside analogs such as fludarabine (Flu) in combination with i.v. busulfan (Bu) has been shown to be highly effective as a pretransplant conditioning regimen in acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS). Because leukemia relapse remains the leading cause of death after allo-SCT, we studied whether clofarabine (Clo), a nucleoside analog with potent antileukemia activity, can be used to complement Flu. In a preliminary report, we previously showed the safety and efficacy of Clo ± Flu with i.v. Bu in 51 patients with high-risk AML, CML, and MDS. The study has now been completed, and we present long-term follow-up data on the entire 70-patient population, which included 49 (70%), 8 (11%), and 13 (19%) patients with AML, MDS, and CML, respectively. Thirteen patients (19%) were in complete remission, and 41 patients (59%) received matched unrelated donor grafts. Engraftment was achieved in all patients. Sixty-three patients (90%) achieved complete remission. There were no deaths reported at day +30, and the 100-day nonrelapse mortality rate was 4% (n = 3). Thirty-one percent of patients (n = 22) developed grades II to IV acute graft-versus-host disease, and the median overall survival and progression-free survival times were 2.4 years and .9 years, respectively. Our results confirm the safety and overall and progression-free survival advantage of the arms with higher Clo doses and lower Flu doses, which was most prominent in the AML/MDS group., (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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9. Allogeneic Transplantation in First Remission Improves Outcomes Irrespective of FLT3-ITD Allelic Ratio in FLT3-ITD-Positive Acute Myelogenous Leukemia.
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Oran B, Cortes J, Beitinjaneh A, Chen HC, de Lima M, Patel K, Ravandi F, Wang X, Brandt M, Andersson BS, Ciurea S, Santos FP, de Padua Silva L, Shpall EJ, Champlin RE, Kantarjian H, and Borthakur G
- Subjects
- Aged, Consolidation Chemotherapy mortality, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Nucleophosmin, Prognosis, Propensity Score, Recurrence, Remission Induction, Survival Analysis, Tandem Repeat Sequences, Transplantation, Homologous, Treatment Outcome, fms-Like Tyrosine Kinase 3 genetics, Alleles, Consolidation Chemotherapy methods, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
- Abstract
The adverse prognosis of internal tandem duplication in the FMS-like tyrosine kinase 3 gene(s) (FLT3-ITD) in patients with acute myelogenous leukemia (AML) may depend on allelic burden. We compared postremission treatment with chemotherapy and hematopoietic stem cell transplantation (HSCT) in 169 FLT3-ITDmut intermediate cytogenetic risk AML patients with allelic ratio evaluable at diagnosis who achieved first complete remission (CR1) with induction therapy. To minimize selection bias, the analysis was limited to patients who remained in CR1 for at least 4 months (median time to HSCT) after achieving CR1, and propensity score matching was implemented. Sensitivity analysis including patients who remained in CR1 for at least 3 months was applied as well. HSCT in CR1 was associated with longer relapse-free survival (RFS) and overall survival (OS), with 3-year estimated rates of 18% and 24%, respectively (P < .001), for patients receiving chemotherapy and 46% and 54%, respectively (P < .001), for those undergoing HSCT. Multivariate regression models showed that HSCT remained statistically significant with improved RFS and OS independent of FLT3-ITD allelic ratio and NPM1 status. Irrespective of postremission therapy, relapse remains the main reason for treatment failure, with a 3-year incidence of 68% in chemotherapy recipients versus 41% in HSCT recipients. Allogeneic HSCT improved disease outcomes compared with chemotherapy after propensity score matching was applied. The improvement observed for RFS (hazard ratio [HR], 0.55; P = .09) and OS (HR, 0.58; P = .10) with HSCT as postremission therapy in patients who remained in CR1 for at least 4 months did not reach statistical significance; however, the sensitivity analyses including patients who remained in CR1 for at least 3 months showed significant improvement in both RFS (HR, 0.31; P = .002) and OS (HR, 0.27; P = .02) after propensity score matching. Our results indicate that HSCT in CR1 for AML FLT3-ITDmut patients is associated with longer RFS and OS. Innovative transplantation strategies to improve relapse incidence are urgently needed., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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10. Pure Red Cell Aplasia in Major ABO-Mismatched Allogeneic Hematopoietic Stem Cell Transplantation Is Associated with Severe Pancytopenia.
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Aung FM, Lichtiger B, Rondon G, Yin CC, Alousi A, Ahmed S, Andersson BS, Bashir Q, Ciurea SO, Hosing C, Jones R, Kebriaei P, Khouri I, Nieto Y, Oran B, Parmar S, Qazilbash M, Shah N, Shpall EJ, Champlin RE, and Popat U
- Subjects
- Adult, Aged, Allografts, Female, Humans, Male, Middle Aged, Retrospective Studies, Time Factors, ABO Blood-Group System, Hematopoietic Stem Cell Transplantation, Pancytopenia blood, Pancytopenia etiology, Pancytopenia mortality, Red-Cell Aplasia, Pure blood, Red-Cell Aplasia, Pure mortality, Red-Cell Aplasia, Pure therapy, Severity of Illness Index
- Abstract
In major ABO-mismatched allogeneic hematopoietic stem cell transplantation (HSCT) persistence of antidonor isohemagglutinins leads to pure red cell aplasia (PRCA). To investigate severe pancytopenia noted in a previous study of PRCA, we analyzed all major ABO-mismatched HSCT between January 2003 and December 2012. Of 83 PRCA patients, 13 (16%) had severe pancytopenia. Severe pancytopenia was defined as an absolute neutrophil count (ANC) < 1.5 K/μL or requiring granulocyte colony-stimulating factor, platelets < 50 K/μL or transfusion dependent, and PRCA with RBC transfusion dependence at post-transplant day 90. In 6 patients (46%) severe pancytopenia resolved after PRCA resolution. Two patients (15%) received a second transplant because of persistent pancytopenia/secondary graft failure, 1 (8%) died from secondary graft failure despite a stem cell boost, 1 (8%) did not recover his platelet counts despite RBC/ANC recovery, and 3 patients (23%) died from disease relapse. We found that severe pancytopenia is frequently associated with PRCA in 16% of major ABO-incompatible HSCT with a higher incidence in males and pancytopenia resolved with resolution of PRCA in 46% of patients., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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11. Treatment with Hypomethylating Agents before Allogeneic Stem Cell Transplant Improves Progression-Free Survival for Patients with Chronic Myelomonocytic Leukemia.
- Author
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Kongtim P, Popat U, Jimenez A, Gaballa S, El Fakih R, Rondon G, Chen J, Bueso-Ramos C, Borthakur G, Pemmaraju N, Garcia-Manero G, Kantarjian H, Alousi A, Hosing C, Anderlini P, Khouri IF, Kebriaei P, Andersson BS, Oran B, Rezvani K, Marin D, Shpall EJ, Champlin RE, and Ciurea SO
- Subjects
- Adenine Nucleotides administration & dosage, Adolescent, Adult, Aged, Allografts, Arabinonucleosides administration & dosage, Clofarabine, Cytarabine administration & dosage, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Retrospective Studies, Survival Rate, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Stem Cell Transplantation
- Abstract
The treatment of patients with chronic myelomonocytic leukemia (CMML) with transplant has not been optimized. We retrospectively reviewed the data for 83 consecutive patients with CMML (47 with CMML-1/2 and 36 with CMML progressed to acute myeloid leukemia) who received an allogeneic stem cell transplant (allo-SCT) at our institution between April 1991 and December 2013 to identify factors associated with improved survival and determine whether treatment with hypomethylating agents before transplant improves progression-free survival (PFS). The median age of the cohort was 57 years. Seventy-eight patients received induction treatment before transplant, with 37 receiving hypomethylating agents and 41 receiving cytotoxic chemotherapy. Patients treated with a hypomethylating agent had a significantly lower cumulative incidence of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; P = .03), whereas treatment-related mortality at 1 year post-transplant did not significantly differ between the groups (27% and 30%, respectively; P = .84). The lower relapse rate resulted in a significantly higher 3-year PFS rate in patients treated with a hypomethylating agent (43%) than in those treated with other agents (27%; P = .04). Our data support the use of hypomethylating agents before allo-SCT for patients with CMML to achieve morphologic remission and improve PFS of these patients. Future studies are needed to confirm these findings., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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12. Mixed T Lymphocyte Chimerism after Allogeneic Hematopoietic Transplantation Is Predictive for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes.
- Author
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Lee HC, Saliba RM, Rondon G, Chen J, Charafeddine Y, Medeiros LJ, Alatrash G, Andersson BS, Popat U, Kebriaei P, Ciurea S, Oran B, Shpall E, and Champlin R
- Subjects
- Adult, Busulfan therapeutic use, Female, Graft Survival, Graft vs Host Disease immunology, Graft vs Host Disease mortality, Graft vs Host Disease pathology, Graft vs Host Disease prevention & control, Humans, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Myelodysplastic Syndromes immunology, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes pathology, Prognosis, Recurrence, Remission Induction, Retrospective Studies, Survival Analysis, T-Lymphocytes pathology, Transplantation Chimera, Transplantation, Homologous, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy, Myeloablative Agonists therapeutic use, Myelodysplastic Syndromes therapy, T-Lymphocytes immunology, Transplantation Conditioning
- Abstract
Chimerism testing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represents a promising tool for predicting disease relapse, although its precise role in this setting remains unclear. We investigated the predictive value of T lymphocyte chimerism analysis at 90 to 120 days after allo-HSCT in 378 patients with AML/MDS who underwent busulfan/fludarabine-based myeloablative preparative regimens. Of 265 (70%) patients with available T lymphocyte chimerism data, 43% of patients in first or second complete remission (CR1/CR2) at the time of transplantation had complete (100%) donor T lymphocytes at day +90 to +120 compared with 60% of patients in the non-CR1/CR2 cohort (P = .005). In CR1/CR2 patients, donor T lymphocyte chimerism ≤ 85% at day +90 to +120 was associated with a higher frequency of 3-year disease progression (29%; 95% confidence interval [CI], 18% to 46% versus 15%; 95% CI, 9% to 23%; hazard ratio [HR], 2.1; P = .04). However, in the more advanced, non-CR1/CR2 cohort, mixed T lymphocyte chimerism was not associated with relapse (37%; 95% CI, 20% to 66% versus 34%; 95% CI, 25% to 47%; HR, 1.3; P = .60). These findings demonstrate that early T lymphocyte chimerism testing at day +90 to +120 is a useful approach for predicting AML/MDS disease recurrence in patients in CR1/CR2 at the time of transplantation., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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13. Vorinostat Combined with High-Dose Gemcitabine, Busulfan, and Melphalan with Autologous Stem Cell Transplantation in Patients with Refractory Lymphomas.
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Nieto Y, Valdez BC, Thall PF, Ahmed S, Jones RB, Hosing C, Popat U, Shpall EJ, Qazilbash M, Gulbis A, Anderlini P, Alousi A, Shah N, Bashir Q, Liu Y, Oki Y, Hagemeister F, Fanale M, Dabaja B, Pinnix C, Champlin R, and Andersson BS
- Subjects
- Adolescent, Adult, Aged, Busulfan therapeutic use, Deoxycytidine analogs & derivatives, Deoxycytidine therapeutic use, Drug Administration Schedule, Female, Follow-Up Studies, Hodgkin Disease immunology, Hodgkin Disease mortality, Hodgkin Disease pathology, Humans, Lymphoma, Large B-Cell, Diffuse immunology, Lymphoma, Large B-Cell, Diffuse mortality, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, T-Cell immunology, Lymphoma, T-Cell mortality, Lymphoma, T-Cell pathology, Male, Melphalan therapeutic use, Middle Aged, Recurrence, Survival Analysis, Transplantation, Autologous, Vorinostat, Gemcitabine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation, Hodgkin Disease therapy, Hydroxamic Acids therapeutic use, Lymphoma, Large B-Cell, Diffuse therapy, Lymphoma, T-Cell therapy, Transplantation Conditioning methods
- Abstract
More active high-dose regimens are needed for refractory/poor-risk relapsed lymphomas. We previously developed a regimen of infusional gemcitabine/busulfan/melphalan, exploiting the synergistic interaction. Its encouraging activity in refractory lymphomas led us to further enhance its use as a platform for epigenetic modulation. We previously observed increased cytotoxicity in refractory lymphoma cell lines when the histone deacetylase inhibitor vorinostat was added to gemcitabine/busulfan/melphalan, which prompted us to clinically study this four-drug combination. Patients ages 12 to 65 with refractory diffuse large B cell lymphoma (DLCL), Hodgkin (HL), or T lymphoma were eligible. Vorinostat was given at 200 mg/day to 1000 mg/day (days -8 to -3). Gemcitabine was infused continuously at 10 mg/m(2)/minute over 4.5 hours (days -8 and -3). Busulfan dosing targeted 4000 μM-minute/day (days -8 to -5). Melphalan was infused at 60 mg/m(2)/day (days -3 and -2). Patients with CD20(+) tumors received rituximab (375 mg/m(2), days +1 and +8). We enrolled 78 patients: 52 DLCL, 20 HL, and 6 T lymphoma; median age 44 years (range, 15 to 65); median 3 prior chemotherapy lines (range, 2 to 7); and 48% of patients had positron emission tomography-positive tumors at high-dose chemotherapy (29% unresponsive). The vorinostat dose was safely escalated up to 1000 mg/day, with no treatment-related deaths. Toxicities included mucositis and dermatitis. Neutrophils and platelets engrafted promptly. At median follow-up of 25 (range, 16 to 41) months, event-free and overall survival were 61.5% and 73%, respectively (DLCL) and 45% and 80%, respectively (HL). In conclusion, vorinostat/gemcitabine/busulfan/melphalan is safe and highly active in refractory/poor-risk relapsed lymphomas, warranting further evaluation. This trial was registered at ClinicalTrials.gov (NCI-2011-02891)., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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14. Can a female donor for a male recipient decrease the relapse rate for patients with acute myeloid leukemia treated with allogeneic hematopoietic stem cell transplantation?
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Kongtim P, Di Stasi A, Rondon G, Chen J, Adekola K, Popat U, Oran B, Kebriaei P, Andersson BS, Champlin RE, and Ciurea SO
- Subjects
- Adolescent, Adult, Age Factors, Allografts, Disease-Free Survival, Female, Humans, Male, Middle Aged, Recurrence, Survival Rate, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy
- Abstract
The mismatched minor histocompatibility antigens present on Y chromosome (H-Y) in male recipients receiving stem cells from female donors may contribute to the graft-versus-leukemia effect and results in a reduced relapse rate, especially in patients with high-risk disease. We retrospectively compared the outcomes of male patients with acute myeloid leukemia who received an allogeneic hematopoietic stem cell transplant (HSCT) from female donors (F-M) (174 patients) versus other gender combinations (667 patients). Median age was 50 years (range, 18 to 74 years). For the whole group, the 1-year cumulative incidence of relapse was significantly lower in F-M group (34.1% versus 41.3%, P = .044), whereas nonrelapse mortality (NRM) was higher (23.2% versus 15.7%, P = .004). For patients younger than 50 years beyond first complete remission, the F-M group was associated with lower relapse rate (42.5% versus 55.2%, P = .045) whereas NRM was not significantly different (35.8% versus 25.5%, P = .141). Although survival was not significantly improved, transplantation from a female donor for male recipient was associated with a lower relapse rate. When relapse is the most common concern for treatment failure, especially for younger patients, a female donor for a male recipient might be beneficial to decrease relapse rate after transplantation. Future studies are needed to explore how the H-Y mismatch may improve survival after transplantation., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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15. Outcomes of thalassemia patients undergoing hematopoietic stem cell transplantation by using a standard myeloablative versus a novel reduced-toxicity conditioning regimen according to a new risk stratification.
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Anurathapan U, Pakakasama S, Mekjaruskul P, Sirachainan N, Songdej D, Chuansumrit A, Charoenkwan P, Jetsrisuparb A, Sanpakit K, Pongtanakul B, Rujkijyanont P, Meekaewkunchorn A, Sruamsiri R, Ungkanont A, Issaragrisil S, Andersson BS, and Hongeng S
- Subjects
- Adolescent, Adult, Allografts, Busulfan administration & dosage, Child, Child, Preschool, Cyclophosphamide administration & dosage, Disease-Free Survival, Humans, Male, Myeloablative Agonists administration & dosage, Risk Factors, Survival Rate, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Hematopoietic Stem Cell Transplantation, Thalassemia mortality, Thalassemia therapy, Transplantation Conditioning methods
- Abstract
Improving outcomes among class 3 thalassemia patients receiving allogeneic hematopoietic stem cell transplantations (HSCT) remains a challenge. Before HSCT, patients who were ≥ 7 years old and had a liver size ≥ 5 cm constitute what the Center for International Blood and Marrow Transplant Research defined as a very high-risk subset of a conventional high-risk class 3 group (here referred to as class 3 HR). We performed HSCT in 98 patients with related and unrelated donor stem cells. Seventy-six of the patients with age < 10 years received the more conventional myeloablative conditioning (MAC) regimen (cyclophosphamide, busulfan, ± fludarabine); the remaining 22 patients with age ≥ 10 years and hepatomegaly (class 3 HR), and in several instances additional comorbidity problems, underwent HSCT with a novel reduced-toxicity conditioning (RTC) regimen (fludarabine and busulfan). We then compared the outcomes between these 2 groups (MAC versus RTC). Event-free survival (86% versus 90%) and overall survival (95% versus 90%) were not significantly different between the respective groups; however, there was a higher incidence of serious treatment-related complications in the MAC group, and although we experienced 6 graft failures in the MAC group (8%), there were none in the RTC group. Based on these results, we suggest that (1) class 3 HR thalassemia patients can safely receive HSCT with our novel RTC regimen and achieve the same excellent outcome as low/standard-risk thalassemia patients who received the standard MAC regimen, and further, (2) that this novel RTC approach should be tested in the low/standard-risk patient population., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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16. Synergistic cytotoxicity of sorafenib with busulfan and nucleoside analogs in human FMS-like tyrosine kinase 3 internal tandem duplications-positive acute myeloid leukemia cells.
- Author
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Song G, Valdez BC, Li Y, Liu Y, Champlin RE, and Andersson BS
- Subjects
- Adenine Nucleotides administration & dosage, Apoptosis drug effects, Arabinonucleosides administration & dosage, Busulfan administration & dosage, Clofarabine, DNA Damage, Drug Synergism, Humans, Leukemia, Myeloid, Acute enzymology, Leukemia, Myeloid, Acute genetics, Niacinamide administration & dosage, Niacinamide pharmacology, Phenylurea Compounds administration & dosage, Phosphorylation, Sorafenib, Tandem Repeat Sequences, Vidarabine administration & dosage, Vidarabine pharmacology, Adenine Nucleotides pharmacology, Antineoplastic Combined Chemotherapy Protocols pharmacology, Arabinonucleosides pharmacology, Busulfan pharmacology, Leukemia, Myeloid, Acute drug therapy, Niacinamide analogs & derivatives, Phenylurea Compounds pharmacology, Vidarabine analogs & derivatives, fms-Like Tyrosine Kinase 3 genetics
- Abstract
Clofarabine (Clo), fludarabine (Flu), and busulfan (Bu) are used in pretransplantation conditioning therapy for patients with myeloid leukemia. To further improve their efficacy in FMS-like tyrosine kinase 3 internal tandem duplications (FLT3-ITD)-positive acute myeloid leukemia (AML), we investigated their synergism with sorafenib (Sor). Exposure of FLT3-ITD-positive MV-4-11 and MOLM 13 cells to Bu+Clo+Flu+Sor resulted in synergistic cytotoxicity; no such synergism was observed in the FLT3-wild type THP-1 and KBM3/Bu250(6) cell lines. The drug synergism in MV-4-11 cells could be attributed to activation of DNA damage response, histone 3 modifications, inhibition of prosurvival kinases, and activation of apoptosis. Further, the phosphorylation of kinases, including FLT3, MAPK kinase (MEK), and AKT, was inhibited. The FLT3-ITD substrate STAT5 and its target gene PIM 2 product decreased when cells were exposed to Sor alone, Bu+Clo+Flu, and Bu+Clo+Flu+Sor. The level of the proapoptotic protein p53 upregulated modulator of apoptosis (PUMA) increased, whereas the level of prosurvival protein MCL-1 decreased when cells were exposed to Bu+Clo+Flu+Sor. The interactions of PUMA with MCL-1 and/or BCL-2 were enhanced when cells were exposed to Bu+Clo+Flu or Bu+Clo+Flu+Sor. The changes in the level of these proteins, which are involved in mitochondrial control of apoptosis, correlate with changes in mitochondrial membrane potential. Bu+Clo+Flu+Sor decreased mitochondrial membrane potential by 60% and caused leakage of cytochrome c, second mitochondria-derived activator of caspases (SMAC)/direct IAP Binding protein with low pI (DIABLO), and AIF from the mitochondria to the cytoplasm, caspase activation, and cell death, suggesting the activation of apoptosis. Analogous, synergistic cytotoxicity in response to Bu, Clo, Flu, and Sor was observed in mononuclear cells isolated from FLT3-ITD-positive AML patients. Although our previous studies were aimed at standardizing the conditioning regimen, the new findings suggest that patients with abnormal expression of FLT3 might further benefit from individualizing treatment through the addition of Sor to Bu+Clo+Flu, thereby providing personalized pretransplantation therapy., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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17. Increasing chimerism after allogeneic stem cell transplantation is associated with longer survival time.
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Tang X, Alatrash G, Ning J, Jakher H, Stafford P, Zope M, Shpall EJ, Jones RB, Champlin RE, Thall PF, and Andersson BS
- Subjects
- Cytogenetics, Disease-Free Survival, Female, Humans, Male, Middle Aged, Prognosis, Survival Analysis, Chimerism drug effects, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning methods, Transplantation, Homologous methods
- Abstract
Donor chimerism after allogeneic stem cell transplantation (allo-SCT) is commonly used to predict overall survival (OS) and disease-free survival (DFS). Because chimerism is observed at 1 or more times after allo-SCT and not at baseline, if chimerism is in fact associated with OS or DFS, then the occurrence of either disease progression or death informatively censors (terminates) the observed chimerism process. This violates the assumptions underlying standard statistical regression methods for survival analysis, which may lead to biased conclusions. To assess the association between the longitudinal post-allo-SCT donor chimerism process and OS or DFS, we analyzed data from 195 patients with acute myelogenous leukemia (n = 157) or myelodysplastic syndrome (n = 38) who achieved complete remission after allo-SCT following a reduced-toxicity conditioning regimen of fludarabine/intravenous busulfan. Median follow-up was 31 months (range, 1.1 to 105 months). Fitted joint longitudinal-survival time models showed that a binary indicator of complete (100%) donor chimerism and increasing percent of donor T cells were significantly associated with longer OS, whereas decreasing percent of donor T cells was highly significantly associated with shorter OS. Our analyses illustrate the usefulness of modeling repeated post-allo-SCT chimerism measurements as individual longitudinal processes jointly with OS and DFS to estimate their relationships., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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18. Pretransplant immunosuppression followed by reduced-toxicity conditioning and stem cell transplantation in high-risk thalassemia: a safe approach to disease control.
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Anurathapan U, Pakakasama S, Rujkijyanont P, Sirachainan N, Songdej D, Chuansumrit A, Sirireung S, Charoenkwan P, Jetsrisuparb A, Issaragrisil S, Ungkanont A, Sruamsiri R, Srisala S, Andersson BS, and Hongeng S
- Subjects
- Adolescent, Antilymphocyte Serum administration & dosage, Busulfan administration & dosage, Child, Female, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Immunosuppression Therapy methods, Male, Risk Factors, Transplantation Chimera, Transplantation Conditioning adverse effects, Transplantation, Homologous, Treatment Outcome, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Hematopoietic Stem Cell Transplantation methods, Thalassemia drug therapy, Thalassemia surgery, Transplantation Conditioning methods
- Abstract
Patients with class 3 thalassemia with high-risk features for adverse events after high-dose chemotherapy with hematopoietic stem cell transplantation (HSCT) are difficult to treat, tending to either suffer serious toxicity or fail to establish stable graft function. We performed HSCT in 18 such patients age ≥7 years and hepatomegaly using a novel approach with pretransplant immunosuppression followed by a myeloablative reduced-toxicity conditioning regimen (fludarabine and i.v. busulfan [Flu-IV Bu]) and then HSCT. The median patient age was 14 years (range, 10 to 18 years). Before the Flu-IV Bu + antithymocyte globulin conditioning regimen, all patients received 1 to 2 cycles of pretransplant immunosuppression with fludarabine and dexamethasone. Thirteen patients received a related donor graft, and 5 received an unrelated donor graft. An initial prompt engraftment of donor cells with full donor chimerism was observed in all 18 patients, but 2 patients developed secondary mixed chimerism that necessitated withdrawal of immunosuppression to achieve full donor chimerism. Two patients (11%) had acute grade III-IV graft-versus-host disease, and 5 patients had limited chronic graft-versus-host disease. The only treatment-related mortality was from infection, and with a median follow-up of 42 months (range, 4 to 75), the 5-year overall survival and thalassemia-free survival were 89%. We conclude that this novel sequential immunoablative pretransplantation conditioning program is safe and effective for patients with high-risk class 3 thalassemia exhibiting additional comorbidities., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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19. Ex vivo T cell-depleted versus unmodified allografts in patients with acute myeloid leukemia in first complete remission.
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Bayraktar UD, de Lima M, Saliba RM, Maloy M, Castro-Malaspina HR, Chen J, Rondon G, Chiattone A, Jakubowski AA, Boulad F, Kernan NA, O'Reilly RJ, Champlin RE, Giralt S, Andersson BS, and Papadopoulos EB
- Subjects
- Adult, Aged, Antilymphocyte Serum administration & dosage, Busulfan administration & dosage, Female, Graft vs Host Disease immunology, Graft vs Host Disease mortality, Graft vs Host Disease pathology, Humans, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute pathology, Male, Melphalan administration & dosage, Middle Aged, Recurrence, Remission Induction, Retrospective Studies, Survival Analysis, T-Lymphocytes pathology, Thiotepa administration & dosage, Transplantation, Homologous, Treatment Outcome, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Antineoplastic Combined Chemotherapy Protocols, Bone Marrow Transplantation, Graft vs Host Disease therapy, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy, Lymphocyte Depletion, T-Lymphocytes immunology
- Abstract
This study was conducted to retrospectively compare the clinical outcomes after transplantation of T cell-depleted (TCD) and unmodified allografts in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Patients received TCD grafts at Memorial Sloan-Kettering Cancer Center (MSKCC, N = 115) between 2001 and 2010 using the following preparative regimens: hyperfractionated total body irradiation (HFTBI)+thiotepa+fludarabine; HFTBI+thiotepa+cyclophosphamide; or i.v. busulfan+melphalan+fludarabine. TCD was performed by 1 of 2 immunomagnetic CD34(+) cell selection methods for peripheral blood grafts or by soybean lectin agglutination followed by sheep red blood cell-rosette depletion for bone marrow grafts. No additional graft-versus-host disease (GVHD) prophylaxis was administered. Patients received unmodified grafts at M.D. Anderson Cancer Center (MDACC, N = 181) after conditioning with busulfan+fludarabine and GVHD prophylaxis with tacrolimus+mini-methotrexate. Patients with unrelated or human leukocyte antigen-mismatched donors received anti-thymocyte globulin (ATG) at both centers, with some recipients of matched related donor TCD transplants also receiving ATG, depending upon the preparative regimen. TCD graft recipients were more likely to be older, receive a mismatched transplant, and have peripheral blood used as the graft source. The incidences rates of grades 2 to 4 acute GVHD and chronic GVHD were significantly lower in the TCD graft group (5% versus 18%, and 13% versus 53%). Three-year relapse-free and overall survival rates were 58% and 57%, respectively, in recipients of TCD grafts, and 60% and 66% in recipients of unmodified grafts (P = not significant). Survival and relapse-free survival are similar after TCD and conventional transplants from related/unrelated donors in patients with AML in CR1, but TCD significantly reduces GVHD., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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20. High-dose chemotherapy and autologous stem cell transplantation for nodular lymphocyte-predominant Hodgkin lymphoma.
- Author
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Karuturi M, Hosing C, Fanale M, Medeiros LJ, Alousi AM, de Lima MJ, Qazilbash MH, Kebriaei P, Younes A, Khouri I, Andersson BS, Champlin R, Anderlini P, and Popat U
- Subjects
- Adolescent, Adult, Antineoplastic Agents administration & dosage, Combined Modality Therapy, Female, Follow-Up Studies, Hodgkin Disease immunology, Hodgkin Disease mortality, Hodgkin Disease pathology, Humans, Male, Middle Aged, Recurrence, Retrospective Studies, Survival Analysis, Transplantation, Autologous, Antineoplastic Agents therapeutic use, Hematopoietic Stem Cell Transplantation, Hodgkin Disease drug therapy
- Abstract
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a distinct subtype of Hodgkin lymphoma that is characterized by unique clinical presentation, histological appearance, and indolent disease course. The recurrent nature of disease provides an opportunity to examine the role of stem cell transplantation in its management. We report here a single-center experience of 26 patients with relapsed NLPHL treated with high-dose chemotherapy and autologous stem cell transplantation between 1990 and 2008. With a median follow-up of 50 months (range, 2-138 months), the 5-year overall and event-free survival were 76% (SE 10%) and 69% (SE 10%), respectively. Our data suggest that high-dose chemotherapy and autologous transplantation should be considered as an option for patients with relapsed NLPHL., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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21. Significance of persistent cytogenetic abnormalities on myeloablative allogeneic stem cell transplantation in first complete remission.
- Author
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Oran B, Popat U, Rondon G, Ravandi F, Garcia-Manero G, Abruzzo L, Andersson BS, Bashir Q, Chen J, Kebriaei P, Khouri IF, Koca E, Qazilbash MH, Champlin R, and de Lima M
- Subjects
- Adult, Disease-Free Survival, Female, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Neoplasm, Residual genetics, Neoplasm, Residual pathology, Prognosis, Remission Induction, Transplantation, Homologous, Chromosome Aberrations, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute surgery
- Abstract
Risk stratification is important to identify patients with acute myelogenous leukemia (AML) who might benefit from allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission. We retrospectively studied 150 patients with AML and diagnostic cytogenetic abnormalities who underwent myeloablative allo-HSCT while in first complete remission to evaluate the prognostic impact of persistent cytogenetic abnormalities at allo-HSCT. Three risk groups were identified. Patients with favorable/intermediate cytogenetics at diagnosis (n = 49) and patients with unfavorable cytogenetics at diagnosis but without a persistent abnormal clone at allo-HSCT (n = 83) had a similar 3-year leukemia-free survival of 58%-60% despite the higher 3-year relapse incidence (RI) in the latter group (32.3%, versus 16.8% in the former group). A third group of patients with unfavorable cytogenetics at diagnosis and a persistent abnormal clone at allo-HSCT (n = 15) had the worst prognosis, with a 3-year RI of 57.5% and 3-year leukemia-free survival of only 29.2%. These data suggest that patients with AML and unfavorable cytogenetics at diagnosis and a persistent abnormal clone at allo-HSCT are at high risk for relapse after allo-HSCT. These patients should be considered for clinical trials designed to optimize conditioning regimens and/or to use preemptive strategies in the posttransplantion setting aimed at decreasing RI., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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22. Clofarabine combined with busulfan provides excellent disease control in adult patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation.
- Author
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Kebriaei P, Basset R, Ledesma C, Ciurea S, Parmar S, Shpall EJ, Hosing C, Khouri I, Qazilbash M, Popat U, Alousi A, Nieto Y, Jones RB, de Lima M, Champlin RE, and Andersson BS
- Subjects
- Adenine Nucleotides administration & dosage, Adenine Nucleotides adverse effects, Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Arabinonucleosides administration & dosage, Arabinonucleosides adverse effects, Busulfan administration & dosage, Busulfan adverse effects, Clofarabine, Female, Humans, Male, Middle Aged, Prospective Studies, Transplantation Conditioning methods, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation methods, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma surgery
- Abstract
We investigated the safety and early disease control data for i.v. busulfan (Bu) in combination with clofarabine (Clo) in patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation (SCT). Fifty-one patients (median age, 36 years; range, 20-64 years) received a matched sibling (n = 24), syngeneic (n = 2), or matched unrelated donor transplant (n = 25) for acute lymphoblastic leukemia in first complete remission (n = 30), second complete remission (n = 13), or active disease (n = 8). More than one-half of the patients had a high-risk cytogenetic profile, as defined by the presence of t(9;22) (n = 17), t(4;11) (n = 3), or complex cytogenetics (n = 7). Clo 40 mg/m(2) was given once daily, with each dose followed by pharmacokinetically dosed Bu infused over 3 hours daily for 4 days, followed by hematopoietic SCT 2 days later. The Bu dose was based on drug clearance, as determined by the patient's response to a 32-mg/m(2) Bu test dose given 48 hours before the high-dose regimen. The target daily area under the receiver-operating characteristic curve was 5500 μM/min for patients age <60 years and 4000 μM/min for those age ≥60 years. The regimen was well tolerated, with a 100-day nonrelapse mortality rate of 6%. With a median follow-up of 14 months among surviving patients (range, 6-28 months), the 1-year overall survival, disease-free survival, and nonrelapse mortality rates were 67% (95% confidence interval [CI], 55%-83%), 54% (95% CI, 41%-71%), and 32% (95% CI, 16%-45%), respectively. For patients undergoing SCT in first remission, these respective rates were 74%, 64%, and 25%. Our data indicate that the combination of Clo and Bu provides effective disease control while maintaining a favorable safety profile., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
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23. Platelet recovery before allogeneic stem cell transplantation predicts posttransplantation outcomes in patients with acute myelogenous leukemia and myelodysplastic syndrome.
- Author
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Alatrash G, Pelosini M, Saliba RM, Koca E, Rondon G, Andersson BS, Chiattone A, Zhang W, Giralt SA, Cernosek AM, Kebriaei P, Alousi AM, Popat UR, Hosing C, Khouri IF, Champlin RE, and de Lima MJ
- Subjects
- Adolescent, Adult, Aged, Blood Platelets drug effects, Child, Cohort Studies, Disease-Free Survival, Female, Humans, Leukemia, Myeloid, Acute drug therapy, Male, Middle Aged, Myelodysplastic Syndromes drug therapy, Prognosis, Remission Induction, Retrospective Studies, Survival Analysis, Treatment Outcome, Young Adult, Blood Platelets physiology, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute blood, Leukemia, Myeloid, Acute surgery, Myelodysplastic Syndromes blood, Myelodysplastic Syndromes surgery, Transplantation Conditioning methods
- Abstract
Complete remission (CR) is the gold standard for assessing outcomes following chemotherapy for acute myelogenous leukemia (AML). "CRp," a response criterion defined as fulfillment of all criteria for CR except platelet count recovery to ≥100 × 10(9)/L, is associated with inferior outcomes following chemotherapy. The prognostic importance of CRp before allogeneic stem cell transplantation (allo-SCT) remains unknown. We analyzed a cohort of AML (n = 334) and myelodysplastic syndrome (MDS; n = 10) patients to determine the prognostic significance of achieving CR versus CRp before allo-SCT. At time of transplantation, 266 patients were in CR (CR1 and ≥CR2) and 78 in CRp (CR1p and ≥CR2p). Median follow-up was 38 months (3-131 months). Overall survival, progression-free survival, and nonrelapse mortality (NRM) were most favorable in patients transplanted in CR (CR1 or ≥CR2) compared with CRp (CR1p or ≥CR2p). Achieving CR is therefore associated with improved posttransplantation outcomes compared with achieving CRp and is a significant prognostic factor that needs to be considered when evaluating AML/MDS patients for clinical trials and allo-SCT., (Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
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24. Myeloablative reduced-toxicity i.v. busulfan-fludarabine and allogeneic hematopoietic stem cell transplant for patients with acute myeloid leukemia or myelodysplastic syndrome in the sixth through eighth decades of life.
- Author
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Alatrash G, de Lima M, Hamerschlak N, Pelosini M, Wang X, Xiao L, Kerbauy F, Chiattone A, Rondon G, Qazilbash MH, Giralt SA, de Padua Silva L, Hosing C, Kebriaei P, Zhang W, Nieto Y, Saliba RM, Champlin RE, and Andersson BS
- Subjects
- Acute Disease, Aged, Busulfan administration & dosage, Disease-Free Survival, Female, Follow-Up Studies, Graft vs Host Disease mortality, Graft vs Host Disease therapy, Humans, Male, Middle Aged, Prospective Studies, Survival Rate, Transplantation, Homologous, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy, Transplantation Conditioning
- Abstract
The optimal pretransplant regimen for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in patients ≥ 55 years of age remains to be determined. The myeloablative reduced-toxicity 4-day regimen i.v. busulfan (Bu) (130 mg/m(2)) and i.v. fludarabine (Flu) (40 mg/m(2)) is associated with low morbidity and mortality. We analyzed 79 patients ≥ 55 years of age (median, 58 years) with AML (n = 63) or MDS (n = 16) treated with i.v. Bu-Flu conditioning regimens between 2001 and 2009 (median follow-up, 24 months). The patients who received this regimen had a good performance status. The 2-year overall survival (OS) rates for patients in first complete remission (CR1), second CR (CR2), or refractory disease and for all patients at time of transplantation were 71%, 44%, 32%, and 46%, respectively; 2-year event-free survival (EFS) rates for patients in CR1, CR2, or refractory disease at time of transplantation and for all patients were 68%, 42%, 30%, and 44%, respectively. One-year transplant-related mortality (TRM) rates for patients who were in CR or who had active disease at the time of transplantation were 19% and 20%, respectively. Grade II-IV acute graft-versus-host (aGVHD) disease was diagnosed in 40% of the patients. Our results suggest that age alone should not be the primary reason for exclusion from receiving myeloablative reduced-toxicity conditioning with i.v. Bu-Flu preceding transplantation in patients with AML/MDS., (Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
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25. Unrelated donor transplantation for acute myelogenous leukemia in first remission.
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Bashir Q, Andersson BS, Fernandez-Vina M, de Padua Silva L, Giralt S, Chiattone A, Wei W, Sharma M, Anderlini P, Shpall EJ, Popat U, Rodrigues M, Champlin RE, and de Lima M
- Subjects
- Adolescent, Adult, Antilymphocyte Serum administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation statistics & numerical data, Busulfan administration & dosage, Clinical Trials as Topic statistics & numerical data, Combined Modality Therapy, Disease-Free Survival, Female, Follow-Up Studies, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Male, Middle Aged, Myeloablative Agonists therapeutic use, Peripheral Blood Stem Cell Transplantation statistics & numerical data, Remission Induction, Retrospective Studies, Salvage Therapy, T-Lymphocytes, Transplantation Conditioning methods, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Young Adult, Bone Marrow Transplantation methods, Leukemia, Myeloid, Acute surgery, Living Donors, Peripheral Blood Stem Cell Transplantation methods, Transplantation, Homologous statistics & numerical data
- Abstract
We retrospectively analyzed the outcomes of all acute myelogenous leukemia (AML) patients in first remission (n = 44; median age = 48 years; high-risk cytogenetics = 59%) who received unrelated donor hematopoietic cell transplantation (HCT) with myeloablative conditioning regimen of i.v. busulfan, fludarabine, and antithymocyte globulin (ATG) between January 2002 and November 2009 at our institution. Donor-recipient pairs were matched by high-resolution HLA-A, -B, -C, -DRB1, and -DQB1 typing (10/10 matches, n = 41; 9/10 matches, n = 3). With a median follow-up of 34 months, actuarial 3-year event-free survival (EFS) and overall survival (OS) is 70% and 78%, respectively. The 3-year EFS and OS in patients with and without poor risk cytogenetics is similar (63% versus 82%, P = 0.43 and 78% versus 82%, P = .89, respectively). The 3-year EFS and OS is also similar in patients above age 55 year versus patients age 55 year or younger (80% versus 67%, P = .47 and 80% versus 78%, P = .81, respectively). The 100-day and 3-year cumulative incidence of transplant-related mortality is 5% and 15%, respectively. Six patients have relapsed, and 3 of them are alive and in remission after salvage therapy, with a median follow-up of 23 months. These results indicate that the majority of AML patients eligible for this treatment can achieve long-term disease control., (2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
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26. Outcomes of patients with myeloid malignancies treated with allogeneic hematopoietic stem cell transplantation from matched unrelated donors compared with one human leukocyte antigen mismatched related donors using HLA typing at 10 loci.
- Author
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Ciurea SO, Saliba RM, Rondon G, Patah PA, Aung F, Cano P, Andersson BS, Kebriaei P, Popat U, Fernandez-Vina M, Champlin RE, and de Lima M
- Subjects
- Alleles, Blood Donors, Female, Graft Rejection immunology, Graft Rejection prevention & control, Graft vs Host Disease genetics, Graft vs Host Disease mortality, Graft vs Host Disease pathology, HLA Antigens genetics, Histocompatibility, Humans, Leukemia, Myeloid genetics, Leukemia, Myeloid mortality, Leukemia, Myeloid pathology, Male, Middle Aged, Retrospective Studies, Risk Factors, Survival Analysis, Transplantation, Transplantation, Homologous, Treatment Outcome, Graft vs Host Disease immunology, HLA Antigens immunology, Hematopoietic Stem Cell Transplantation, Histocompatibility Testing methods, Leukemia, Myeloid immunology, Leukemia, Myeloid therapy
- Abstract
Most candidates for hematopoietic stem cell transplantation (HSCT) lack a human leukocyte antigen (HLA)-identical sibling donor. Some patients may have a related donor with whom they are mismatched at 1 antigen/allele. It is not known whether such a match is preferable to a matched unrelated donor (MUD). We evaluated the outcomes (survival, relapse, nonrelapse mortality [NRM]) of all 28 patients with a single HLA antigen/allele mismatch identified through high-resolution HLA typing at HLA-A, -B, -C, -DRB1, and -DQB1, and all 318 patients with myeloid malignancies who received transplants from a 10/10 MUD treated during the same period of time at a single institution. Overall, outcomes for patients treated from a 1-antigen/allele mismatch related donor were significantly worse than from a MUD, primarily because of increased NRM. Overall survival (OS) rates at 3 years for 1-antigen/allele mismatched related donor and MUD transplant recipients were 19% and 45% (P = .007), and NRM rates were 40% and 26% (P = .05), respectively. Patients with class I mismatches appeared to have poorer OS than did patients with class II mismatches. A higher incidence of graft rejection was identified in the mismatched related donor group (P = .02). These results indicate that transplant outcomes are better with a MUD than with a 1 antigen/allele-mismatched related donor., (Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
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27. Clofarabine ± fludarabine with once daily i.v. busulfan as pretransplant conditioning therapy for advanced myeloid leukemia and MDS.
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Andersson BS, Valdez BC, de Lima M, Wang X, Thall PF, Worth LL, Popat U, Madden T, Hosing C, Alousi A, Rondon G, Kebriaei P, Shpall EJ, Jones RB, and Champlin RE
- Subjects
- Animals, Antilymphocyte Serum, Antineoplastic Agents administration & dosage, Cell Line, Tumor, Clofarabine, Drug Administration Schedule, Drug Resistance, Neoplasm, Drug Synergism, Female, Graft vs Host Disease mortality, Humans, Immunosuppressive Agents administration & dosage, Injections, Intravenous, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Myeloablative Agonists administration & dosage, Rabbits, Remission Induction, Survival Analysis, Tacrolimus, Transplantation, Homologous, Vidarabine administration & dosage, Adenine Nucleotides administration & dosage, Arabinonucleosides administration & dosage, Busulfan administration & dosage, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy, Transplantation Conditioning, Vidarabine analogs & derivatives
- Abstract
Although a combination of i.v. busulfan (Bu) and fludarabine (Flu) is a safe, reduced-toxicity conditioning program for acute myelogenous leukemia/myelodysplastic syndromes (AML/MDS), recurrent leukemia posttransplantation remains a problem. To enhance the conditioning regimen's antileukemic effect, we decided to supplant Flu with clofarabine (Clo), and assayed the interactions of these nucleoside analogs alone and in combination with Bu in Bu-resistant human cell lines in vitro. We found pronounced synergy between each nucleoside and the alkylator but even more enhanced cytotoxic synergy when the nucleoside analogs were combined prior to exposing the cells to Bu. We then designed a 4-arm clinical trial in patients with myeloid leukemia undergoing allogeneic stem cell transplantation (allo-SCT). Patients were adaptively randomized as follows: Arm I-Clo:Flu 10:30 mg/m(2), Arm II-20:20 mg/m(2), Arm III-30:10 mg/m(2), and Arm IV-single-agent Clo at 40 mg/m(2). The nucleoside analog(s) were/was infused over 1 hour once daily for 4 days, followed on each day by Bu, infused over 3 hours to a pharmacokinetically targeted daily area under the curve (AUC) of 6000 μMol-min ± 10%. Fifty-one patients have been enrolled with a minimum follow-up exceeding 100 days. There were 32 males and 19 females, with a median age of 45 years (range: 6-59). Nine patients had chronic myeloid leukemia (CML) (BC: 2, second AP: 3, and tyrosine-kinase inhibitor refractory first chronic phase [CP]: 4). Forty-two patients had AML: 14 were induction failures, 8 in first chemotherapy-refractory relapse, 7 in untreated relapse, 3 in second or subsequent relapse, 4 were in second complete remission (CR), and 3 in second CR without platelet recovery (CRp), 2 were in high-risk CR1. Finally, 1 patient was in first CRp. Graft-versus-host disease (GVHD) prophylaxis was tacrolimus and mini-methorexate (MTX), and those who had an unrelated or 1 antigen-mismatched donor received low-dose rabbit-ATG (Thymoglobulin™). All patients engrafted. Forty-one patients had active leukemia at the time of transplant, and 35 achieved CR (85%). Twenty of the 42 AML patients and 5 of 9 CML patients are alive with a projected median overall survival (OS) of 23 months. Marrow and blood (T cell) chimerism studies at day +100 revealed that both in the lower-dose Clo groups (groups 1+2) and the higher-dose Clo groups (groups 3+4), the patients had a median of 100% donor (T cell)-derived DNA. There has been no secondary graft failure. In the first 100 days, 1 patient died of pneumonia, and 1 of liver GVHD. We conclude that (1) Clo ± Flu with i.v. Bu as pretransplant conditioning is safe in high-risk myeloid leukemia patients; (2) clofarabine is sufficiently immunosuppressive to support allo-SCT in myeloid leukemia; and (3) the median OS of 23 months in this high-risk patient population is encouraging. Additional studies to evaluate the antileukemic efficacy of Clo ± Flu with i.v. Bu as pretransplant conditioning therapy are warranted., (Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
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28. Intravenous busulfan plus melphalan is a highly effective, well-tolerated preparative regimen for autologous stem cell transplantation in patients with advanced lymphoid malignancies.
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Kebriaei P, Madden T, Kazerooni R, Wang X, Thall PF, Ledesma C, Nieto Y, Shpall EJ, Hosing C, Qazilbash M, Popat U, Khouri I, Champlin RE, Jones RB, and Andersson BS
- Subjects
- Adult, Aged, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Agents, Alkylating adverse effects, Antineoplastic Agents, Alkylating pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Busulfan administration & dosage, Busulfan adverse effects, Busulfan pharmacokinetics, Female, Hodgkin Disease drug therapy, Hodgkin Disease therapy, Humans, Infusions, Intravenous, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Non-Hodgkin therapy, Lymphoproliferative Disorders drug therapy, Male, Melphalan administration & dosage, Melphalan adverse effects, Middle Aged, Multiple Myeloma drug therapy, Multiple Myeloma therapy, Severity of Illness Index, Survival Analysis, Transplantation, Autologous, Young Adult, Antineoplastic Agents, Alkylating therapeutic use, Busulfan therapeutic use, Hematopoietic Stem Cell Transplantation, Lymphoproliferative Disorders therapy, Melphalan therapeutic use, Transplantation Conditioning adverse effects
- Abstract
We investigated the administration of intravenous (i.v.) busulfan (Bu) combined with melphalan (Mel) in patients with advanced lymphoid malignancies undergoing autologous stem cell transplantation. Bu 130 mg/m(2) was infused daily for 4 days, either as a fixed dose per body surface area (BSA), or to target an average daily area under the curve of 5000 μmol-min, determined by a test dose of i.v. Bu at 32 mg/m(2) given 48 hours prior to the high-dose regimen, followed by a rest day, followed by 2 daily doses of Mel at 70 mg/m(2). Stem cells were infused the following day. Eighty patients had i.v. Bu delivered per test dose guidance. The median daily systemic Bu exposure was 4867 μmol-min. One hundred two patients (Hodgkin lymphoma n = 49, non-Hodgkin lymphoma n = 12, multiple myeloma = 41) with a median age of 44 years (range: 19-65 years) were treated. The 2-year overall survival and progression-free survival rates were 85% and 57%, respectively, for patients with Hodgkin lymphoma, 67% and 64%, respectively, for patients with non-Hodgkin lymphoma, and 82% and 42%, respectively, for patients with multiple myeloma. The regimen was very well tolerated with treatment-related mortality at 100 days, 1 year, and 2 years of 1%, 3%, and 3%, respectively. Intravenous Bu-Mel was well tolerated. Disease control wa encouraging, and should be explored in larger phase II studies., (Copyright © 2011. Published by Elsevier Inc.)
- Published
- 2011
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29. Generic immunosuppressants in hematopoietic cell transplantation.
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Cutler C, Kesselheim A, Gabardi S, Andersson BS, Carpenter P, Khoury HJ, Litzow M, Rowley SD, Lanum S, Leather H, Tina Shih YC, Gale RP, Wingard JR, Appelbaum FR, and Anasetti C
- Subjects
- Drug Costs, Drug Monitoring, Drugs, Generic adverse effects, Drugs, Generic economics, Drugs, Generic pharmacokinetics, Humans, Immunosuppressive Agents adverse effects, Immunosuppressive Agents economics, Immunosuppressive Agents pharmacokinetics, Mycophenolic Acid adverse effects, Mycophenolic Acid analogs & derivatives, Mycophenolic Acid economics, Mycophenolic Acid pharmacokinetics, Mycophenolic Acid therapeutic use, Patient Education as Topic, Tacrolimus adverse effects, Tacrolimus economics, Tacrolimus pharmacokinetics, Tacrolimus therapeutic use, Therapeutic Equivalency, Drugs, Generic therapeutic use, Hematopoietic Stem Cell Transplantation, Immunosuppression Therapy economics, Immunosuppressive Agents therapeutic use
- Published
- 2011
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30. Allogeneic stem cell transplantation for myelofibrosis with leukemic transformation.
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Ciurea SO, de Lima M, Giralt S, Saliba R, Bueso-Ramos C, Andersson BS, Hosing CM, Verstovsek S, Champlin RE, and Popat U
- Subjects
- Aged, Cell Transformation, Neoplastic, Disease-Free Survival, Female, Humans, Leukemia pathology, Male, Melphalan administration & dosage, Melphalan therapeutic use, Middle Aged, Primary Myelofibrosis pathology, Prognosis, Transplantation Conditioning, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Leukemia therapy, Primary Myelofibrosis therapy
- Abstract
Leukemic transformation (LT) from myelofibrosis has a very poor prognosis with the current treatment strategies. We hypothesized that allogeneic stem cell transplantation (ASCT) can improve outcomes for patients with LT, and reviewed 55 consecutive patients that were treated for myelofibrosis with ASCT at our institution. Fourteen patients (25%) were identified to have LT. Thirteen of these patients received induction chemotherapy and 6 achieved remission at the time of transplant. Conditioning regimen was melphalan (Mel)-based in 9 patients. All patients engrafted and achieved remission after transplant, whereas 4 subsequently relapsed. After a median follow-up of 31 months, 6 patients (49%) survived long term. Although limited by a small number of patients, this study suggests that patients with myelofibrosis and LT may achieve long-term remission after induction chemotherapy and ASCT., (Copyright (c) 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2010
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31. Busulfan in hematopoietic stem cell transplantation.
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Ciurea SO and Andersson BS
- Subjects
- Antineoplastic Agents pharmacokinetics, Antineoplastic Agents therapeutic use, Busulfan pharmacokinetics, Humans, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute therapy, Transplantation Conditioning methods, Busulfan therapeutic use, Hematopoietic Stem Cell Transplantation methods
- Abstract
The development of intravenous busulfan (Bu) and its incorporation in the preparative regimens for allogeneic stem cell transplantation has changed transplantation for myelogenous malignancies. Bypassing the oral route to achieve 100% bioavailability translated into improved control over drug administration, with increased safety and reliability of generating therapeutic Bu levels, maximizing antileukemic efficacy. Bu-nucleoside analog-based conditioning chemotherapy, thus far represented by fludarabine (Flu), is becoming the conditioning chemotherapy regimen of choice for patients with acute myelogenous leukemia (AML) at many transplant centers. The use of busulfan Bu-based conditioning is extending rapidly also to hematopoietic stem cell transplantation (HSCT) for lymphoid malignancies, genetic diseases, and umbilical cord blood transplantation.
- Published
- 2009
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32. Once daily i.v. busulfan and fludarabine (i.v. Bu-Flu) compares favorably with i.v. busulfan and cyclophosphamide (i.v. BuCy2) as pretransplant conditioning therapy in AML/MDS.
- Author
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Andersson BS, de Lima M, Thall PF, Wang X, Couriel D, Korbling M, Roberson S, Giralt S, Pierre B, Russell JA, Shpall EJ, Jones RB, and Champlin RE
- Subjects
- Adolescent, Adult, Antilymphocyte Serum therapeutic use, Antineoplastic Agents therapeutic use, Bayes Theorem, Combined Modality Therapy, Disease-Free Survival, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Infusions, Intravenous, Leukemia, Myeloid, Acute drug therapy, Male, Melphalan administration & dosage, Middle Aged, Myelodysplastic Syndromes drug therapy, Survival Analysis, T-Lymphocytes, Tissue Donors statistics & numerical data, Transplantation, Homologous, Treatment Outcome, Vidarabine administration & dosage, Busulfan administration & dosage, Leukemia, Myeloid, Acute surgery, Myeloablative Agonists administration & dosage, Myelodysplastic Syndromes surgery, Peripheral Blood Stem Cell Transplantation adverse effects, Peripheral Blood Stem Cell Transplantation statistics & numerical data, Transplantation Conditioning methods, Vidarabine analogs & derivatives
- Abstract
We postulated that fludarabine (Flu) instead of cyclophosphamide (Cy) combined with i.v. busulfan (Bu) as preconditioning for allogeneic hematopoietic stem cell transplantation (HSCT) would improve safety and retain antileukemic efficacy. Sixty-seven patients received BuCy2, and subsequently, 148 patients received Bu-Flu. We used a Bayesian method to compare outcomes between these nonrandomized patients. The groups had comparable pretreatment characteristics, except that Bu-Flu patients were older (46 versus 39 years, P < .01), more often had unrelated donors (47.3% versus 20.9%, P < .0003), and had shorter median follow-up (39.7 versus 74.6 months). To account for improved supportive care and other unidentified factors that may affect outcome ("period" effects), 78 acute myelogenous leukemia (AML) patients receiving Melphalan-Flu (MF), treated in parallel during this time (1997-2004) were used to estimate the period effect. The MF patients' outcomes worsened during this period. Therefore, the period effect is unlikely to explain the greatly improved outcome with Bu-Flu. Patients transplanted with Bu-Flu in the first complete remission (CR1) had a 3-year overall survival and event-free-survival (EFS) of 78% and 74%, respectively, whereas CR1 patients younger than age 41 had a 3-year EFS of 83%. These results support replacing BuCy +/- ATG with Bu-Flu +/- rabbit-antithymocyte globulin (ATG), and warrant a prospective comparison between allogeneic HSCT and conventional induction/consolidation chemotherapy for AML in CR1.
- Published
- 2008
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33. High busulfan exposure is associated with worse outcomes in a daily i.v. busulfan and fludarabine allogeneic transplant regimen.
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Geddes M, Kangarloo SB, Naveed F, Quinlan D, Chaudhry MA, Stewart D, Savoie ML, Bahlis NJ, Brown C, Storek J, Andersson BS, and Russell JA
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Area Under Curve, Busulfan toxicity, Drug Monitoring methods, Graft Survival, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation mortality, Humans, Middle Aged, Transplantation Conditioning mortality, Transplantation, Homologous, Treatment Outcome, Vidarabine administration & dosage, Whole-Body Irradiation, Busulfan administration & dosage, Busulfan pharmacokinetics, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning methods, Vidarabine analogs & derivatives
- Abstract
Low plasma busulfan (Bu) area under the concentration-time curve (AUC) is associated with graft failure and relapsed leukemias, and high AUC with toxicities when Bu is used orally or i.v. 4 times daily combined with cyclophosphamide in myeloablative hematopoietic stem cell transplantation (SCT) conditioning regimens. We report Bu AUC and its association with clinical outcomes in 130 patients with hematologic malignancies given a once-daily i.v. Bu (3.2 mg/kg days -5 to -2) and fludarabine (Flu, 50 mg/m(2) days -6 to -2) regimen. Total-body irradiation (TBI) 200 cGy x 2 was added for 51 patients with acute leukemias. Plasma AUC varied 3.6-fold (2184-7794 microM.min, median 4699 microM.min). Patients with an AUC >6000 microM.min had lower overall survival (OS) than those with AUC < or =6000 microM.min at 12 months (38% versus 74%) and 36 months (23% versus 68%, P < .001). This effect was apparent in patients with standard-risk and high-risk disease, and persisted when potential confounders were considered (hazard ratio 3.2, 95% confidence interval 1.7-6.3). Nonrelapse mortality (NRM) at 100 days (6% versus 19%) and progression free survival (PFS; 58% versus 16%) at 3 years were better with AUC < or =6000 microM.min. These data support a role for therapeutic dose monitoring and dose adjustment with daily i.v. busulfan.
- Published
- 2008
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34. Pharmacokinetics of once-daily IV busulfan as part of pretransplantation preparative regimens: a comparison with an every 6-hour dosing schedule.
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Madden T, de Lima M, Thapar N, Nguyen J, Roberson S, Couriel D, Pierre B, Shpall EJ, Jones RB, Champlin RE, and Andersson BS
- Subjects
- Acute Disease, Administration, Oral, Adolescent, Adult, Aged, Area Under Curve, Busulfan blood, Drug Administration Schedule, Drug Interactions, Female, Hematopoietic Stem Cell Transplantation methods, Humans, Infusions, Intravenous, Leukemia, Myeloid therapy, Male, Metabolic Clearance Rate, Middle Aged, Myeloablative Agonists blood, Myelodysplastic Syndromes therapy, Busulfan administration & dosage, Busulfan pharmacokinetics, Myeloablative Agonists administration & dosage, Myeloablative Agonists pharmacokinetics, Transplantation Conditioning methods
- Abstract
In pretransplantation therapy busulfan is typically given every 6 hours. We infused busulfan once daily at 130 mg/m2 for 4 days, performing pharmacokinetic analyses on plasma concentration-time data (n = 60 patients) on days 1, 3, and/or 4. Mean (percent coefficient of variation) maximum concentration, volume of distribution, half-life, and clearance were 3.6 microg/mL (13.8%), 22.6 L/m2 (20.2%), 2.73 hours (27.5%), and 109 mL/min/m2 (26%), respectively. The mean (percent coefficient of variation) and median daily areas under the curve were 4873 (21.8%) and 4871 microM x minute. Intrapatient variability in day-to-day estimated clearance was <20%, without day-to-day drug accumulation. The pharmokinetic parameters were compared with those from 47 patients given intravenous busulfan at approximately 0.8 mg/kg (approximately 32 mg/m2) every 6 hours. We conclude that there is (1) a dose proportionality based on mean and median areas under the curve, (2) unchanged estimated clearance with a 4-fold increase in dose and a 2.5-fold difference in dosing rate, (3) negligible variability in dose-to-dose pharmacokinetics and negligible interdose accumulation with once-daily administration, and (4) no change in pharmokinetic parameter(s) with concomitant use of imidazole antifungals, oral contraceptives, or phenytoin. In summary, intravenous busulfan has highly predictable, linear pharmacokinetics from 32 mg/m2 (approximately 0.8 mg/kg) to 130 mg/m2 (approximately 3.2 mg/kg). Further, once-daily intravenous busulfan dosing is convenient, favoring its more widespread application.
- Published
- 2007
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35. Prognostic factors for outcomes of patients with refractory or relapsed acute myelogenous leukemia or myelodysplastic syndromes undergoing allogeneic progenitor cell transplantation.
- Author
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Wong R, Shahjahan M, Wang X, Thall PF, De Lima M, Khouri I, Gajewski J, Alamo J, Couriel D, Andersson BS, Donato M, Hosing C, Komanduri K, Anderlini P, Molldrem J, Ueno NT, Estey E, Ippoliti C, Champlin R, and Giralt S
- Subjects
- Adult, Aged, Disease-Free Survival, Female, Humans, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Myelodysplastic Syndromes mortality, Retrospective Studies, Transplantation, Homologous, Treatment Outcome, Bone Marrow Transplantation, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes therapy
- Abstract
Allogeneic progenitor cell transplantation is the only curative therapy for patients with refractory acute myelogenous leukemia or myelodysplastic syndromes. To identify prognostic factors in these patients, we performed a retrospective analysis of transplantation outcomes. Patients were selected if they had undergone an allogeneic transplantation between January 1988 and January 2002 and were not in remission or first untreated relapse at the time of transplantation. A total of 135 patients were identified. The median age was 49.5 years (range, 19-75 years). At the time of transplantation, 39.3% of patients had not responded to induction therapy, 37% had not responded to first salvage therapy, and 23.7% were beyond first salvage. Forty-one patients (30%) received unrelated donor progenitor cells. Eighty patients (59%) received either a reduced-intensity or a nonmyeloablative regimen. A total of 104 (77%) of 135 patients died, with a median survival time of 4.9 months (95% confidence interval, 3.9-6.6 months). The median progression-free survival was 2.9 months (95% confidence interval, 2.5-4.2 months). A Cox regression analysis showed that Karnofsky performance status, peripheral blood blasts, and tacrolimus exposure during the first 11 days after transplantation were predictive of survival. These data support the use of allogeneic transplantation for patients with relapsed or refractory acute myelogenous leukemia/myelodysplastic syndromes and suggest that optimal immune suppression early after transplantation is essential for long-term survival even in patients with refractory myeloid leukemias.
- Published
- 2005
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36. Intravenous busulfan in pretransplant chemotherapy: bioavailability and patient benefit.
- Author
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Andersson BS, Kashyap A, Couriel D, Madden T, de Lima M, Thall PF, Fernandez H, Vaughan WP, Jones R, Wingard JR, Blume KG, and Champlin RE
- Subjects
- Administration, Oral, Biological Availability, Busulfan administration & dosage, Busulfan pharmacokinetics, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Injections, Intravenous, Reproducibility of Results, Antineoplastic Agents, Alkylating therapeutic use, Busulfan toxicity, Hematologic Neoplasms therapy
- Published
- 2003
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37. Conditioning therapy with intravenous busulfan and cyclophosphamide (IV BuCy2) for hematologic malignancies prior to allogeneic stem cell transplantation: a phase II study.
- Author
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Andersson BS, Kashyap A, Gian V, Wingard JR, Fernandez H, Cagnoni PJ, Jones RB, Tarantolo S, Hu WW, Blume KG, Forman SJ, and Champlin RE
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols toxicity, Area Under Curve, Busulfan pharmacokinetics, Female, Graft Survival, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Humans, Immunosuppressive Agents toxicity, Infusions, Intravenous, Male, Middle Aged, Stem Cell Transplantation mortality, Survival Analysis, Transplantation Conditioning mortality, Transplantation, Homologous methods, Treatment Outcome, Busulfan administration & dosage, Cyclophosphamide administration & dosage, Hematologic Neoplasms drug therapy, Immunosuppressive Agents administration & dosage, Stem Cell Transplantation methods, Transplantation Conditioning methods
- Abstract
Busulfan (Bu) is commonly used as a component of conditioning regimens for hematopoietic stem cell transplantation. Precise delivery of the oral formulation is compromised by erratic gastrointestinal absorption. An IV Bu formulation was developed to provide dose assurance and complete bioavailability. In a phase I study, the plasma bioequivalence of IV Bu was established at approximately 80% of the oral dose. We now report the findings of the first phase II study, in which 61 adults with hematologic cancers were treated with a Bu-cyclophosphamide (BuCy) regimen consisting of IV Bu (0.8 mg/kg every 6 hours x 16) followed by Cy (60 mg/kg qd x 2) and transplantation of stem cells from an HLA-matched sibling donor. The median age of study participants was 37 years; 75% of patients had active disease; 48% were heavily pretreated, and 13% had undergone a prior transplantation. Median follow-up was 2.3 years; median time to engraftment (absolute neutrophil count, >0.5 x 10(9)/L) was 13 days; 100% of patients with cytogenetic and/or molecular markers had documented chimerism; and there were no engraftment failures. Two-year overall and disease-free survival were 67% and 42%, respectively. There were no unexpected toxic reactions. Fatal veno-occlusive disease occurred in 2 patients, 1 of whom had undergone a prior transplantation. Treatment-related mortality at 100 days was 9.8% (6/61). Bu pharmacokinetics after IV drug administration demonstrated high inter- and intrapatient consistency; 86% of patients maintained an area under the curve between 800 and 1500 microMol-min. In conclusion, the IV Bu in this regimen was very well tolerated and demonstrated excellent antitumor efficacy, most likely because of dose assurance with predictable pharmacokinetics.
- Published
- 2002
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38. Busulfan systemic exposure relative to regimen-related toxicity and acute graft-versus-host disease: defining a therapeutic window for i.v. BuCy2 in chronic myelogenous leukemia.
- Author
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Andersson BS, Thall PF, Madden T, Couriel D, Wang X, Tran HT, Anderlini P, de Lima M, Gajewski J, and Champlin RE
- Subjects
- Acute Disease, Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols toxicity, Area Under Curve, Biological Availability, Busulfan administration & dosage, Cyclophosphamide administration & dosage, Dose-Response Relationship, Drug, Drug-Related Side Effects and Adverse Reactions, Female, Graft vs Host Disease chemically induced, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Humans, Infusions, Intravenous, Leukemia, Myelogenous, Chronic, BCR-ABL Positive mortality, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Male, Middle Aged, Survival Analysis, Transplantation Conditioning adverse effects, Transplantation Conditioning standards, Transplantation, Homologous, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Busulfan pharmacokinetics, Busulfan toxicity, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
- Abstract
Complete bioavailability of i.v. busulfan (Bu) provides dose assurance by reducing the interdose and interpatient variability in Bu systemic exposure (Bu-SE) associated with the oral formulation. We hypothesized that Bu-SE, represented by the area under the plasma concentration versus time curve (AUC), would correlate with treatment outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for chronic myelogenous leukemia (CML). Therefore, we analyzed the risk of death, incidence of regimen-related toxicity, and incidence of acute GVHD (aGVHD) as functions of the per dose i.v. Bu AUC in 36 CML patients who received a HSCT from an HLA-matched family donor after the i.v. BuCy2 regimen. Per-dose Bu AUCs were calculated for each subject using data obtained for doses 1, 5, 9, and 13. Toxicity was evaluated using the modified National Cancer Institute criteria. Because no patient developed veno-occlusive disease, increased serum bilirubin was used to characterize hepatotoxicity. We found that the probabilities of developing gastrointestinal toxicity (P = .01), hepatotoxicity (P < .01), mucositis (P = .09), and aGVHD (P < .01) all increased with increasing AUC. Further, the risk of death was significantly lower for patients having a per-dose AUC between approximately 950 and 1520 microMol-min, whereas the risk increased sharply with either lower or higher AUC values. These data suggest that an optimal Bu therapeutic window, based on per-dose AUC, exists. Given the ability of i.v. Bu to provide a more consistent per-dose AUC, these results should be useful in designing future i.v.V Bu-based treatment protocols for stem cell transplantation.
- Published
- 2002
- Full Text
- View/download PDF
39. Intravenous versus oral busulfan as part of a busulfan/cyclophosphamide preparative regimen for allogeneic hematopoietic stem cell transplantation: decreased incidence of hepatic venoocclusive disease (HVOD), HVOD-related mortality, and overall 100-day mortality.
- Author
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Kashyap A, Wingard J, Cagnoni P, Roy J, Tarantolo S, Hu W, Blume K, Niland J, Palmer JM, Vaughan W, Fernandez H, Champlin R, Forman S, and Andersson BS
- Subjects
- Administration, Oral, Adult, Cyclophosphamide administration & dosage, Female, Hematologic Neoplasms complications, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation mortality, Hepatic Veno-Occlusive Disease mortality, Hepatic Veno-Occlusive Disease prevention & control, Humans, Incidence, Infusions, Intravenous, Male, Middle Aged, Retrospective Studies, Survival Analysis, Transplantation Conditioning adverse effects, Transplantation Conditioning methods, Transplantation, Homologous, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Busulfan administration & dosage, Busulfan toxicity, Hematopoietic Stem Cell Transplantation methods, Hepatic Veno-Occlusive Disease chemically induced
- Abstract
Hepatic venoocclusive disease (HVOD) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT) and is a well-recognized dose-limiting toxicity of oral busulfan (Bu)-based preparative regimens. The unpredictable absorption of oral Bu from the gastrointestinal (GI) tract and hepatic first-pass effects have led to the development of an intravenous Bu preparation (i.v. Bu). The purpose of this retrospective comparison was to evaluate the incidence rate of HVOD and the 100-day mortality rate in patients treated with a busulfan/cyclophosphamide (BuCy2) regimen in which either oral Bu or i.v. Bu was administered. Data from 2 similar groups of patients treated between March 1995 and December 1997 were analyzed. Thirty patients were treated with oral Bu (1 mg/kg x 16 doses) at City of Hope and 61 patients were treated with i.v. Bu (0.8 mg/kg x 16 doses) in a multicenter trial involving 7 sites. Bu was followed by Cy (60 mg/kg x 2 days) and a histocompatible-sibling-donor HSCT. In the i.v. Bu treatment group, 48% of the patients were classified as heavily pretreated (> or = 3 prior chemotherapy regimens, prior radiation, or prior HSCT) with 13% having had a prior HSCT and 75% having active disease at the time of transplantation. According to the same classification criteria, 33% of the patients in the oral-Bu treatment group were considered heavily pretreated, with 23% having had a prior HSCT and 80% having active disease at the time of transplantation. The incidence rates of clinically diagnosed HVOD were 5/61 (8%) and 10/30 (33%) after i.v. and oral Bu, respectively. HVOD-related mortality occurred in 2 (3.3%) of 61 i.v. and 6 (20%) of 30 oral Bu patients. The (standardized) Jones criteria for HVOD were met by 4.9% of i.v. and 20% of oral Bu patients. Univariate logistic regression analysis identified oral versus i.v. Bu (P = .001) and a diagnosis of myelodysplastic syndrome (P = .04) as statistically significant factors in the development of HVOD, with prior extensive treatment identified as marginally significant (P = .25). No other demographic parameter was found to be significant. After adjustment for prior treatment, multivariate analyses showed that the use of oral versus i.v. Bu was the strongest predictor for development of HVOD (odds ratio, 7.5; 95% confidence interval, 2.1-27.2; P = .002). This study showed that the incidence rate of HVOD is significantly lower (P = .002) and the 100-day survival rate significantly higher (P = .002) in patients treated with i.v. Bu than in patients treated with oral Bu when Bu is used as part of a BuCy2 preparative regimen for allogeneic HSCT.
- Published
- 2002
- Full Text
- View/download PDF
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