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PURPOSE Patients with hematologic malignancies are extremely vulnerable to financial toxicity (FT) because of the high costs of treatment and health care utilization. This pilot study identified patients at high risk because of FT and attempted to improve clinical outcomes with comprehensive intervention. METHODS All patients who presented to the Levine Cancer Institute's Leukemia Clinic between May 26, 2019, and March 10, 2020, were screened for inclusion by standardized two question previsit survey. Patients screening positive were enrolled in the comprehensive intervention that used nurse navigators, clinical pharmacists, and community pro bono financial planners. Primary outcomes were defined as improvement in mental and physical quality of life in all patients and improvement in overall survival in the high-risk disease group. RESULTS One hundred seven patients completed comprehensive intervention. Patients experiencing FT had increased rates of noncompliance including to prescription (16.8%) and over-the-counter medications (15.9%). The intervention resulted in statistically significantly higher quality of life when measured by using Patient-Reported Outcomes Measurement Information System physical (12.5 ± 2.2 v 13.7 ± 1.8) and mental health scores (11.4 ± 2.2 v 12.4 ± 2.2; all P < .001). In patients with high-risk disease (as determined by using disease-specific scoring systems), risk of death in those receiving the intervention was 0.44 times the risk of death in those without the intervention after adjusting for race, and treatment with stem-cell transplant, oral chemotherapy, or immunotherapy (95% CI, 0.21 to 0.94; P = .034). CONCLUSION Screening and intervention on FT for patients with hematologic malignancies is associated with increased quality of life and survival. [ABSTRACT FROM AUTHOR]

Background: Aggressive large B‐cell lymphomas (LBCLs) are curable, but previous studies have shown inferior outcomes in minorities. Nurse navigation programs can improve patient outcomes by providing patient support. This study presents the outcomes of White and minority patients with aggressive LBCL at an institution with an active nurse navigation program. Methods: The authors prospectively collected baseline characteristics, treatment regimens, and outcome data for patients with aggressive LBCL. Navigation encounters were characterized as low or high intensity. Overall survival (OS) and progression‐free survival (PFS) were calculated with Kaplan‐Meier methods. Baseline characteristics were compared with Fisher exact tests. Results: Two hundred four consecutive patients (47 minority patients and 157 White patients) were included. Results were presented as minorities versus Whites. There were no differences in prognostic scores (Revised International Prognostic Index score of 3‐5, 43% vs 47%; P =.50), frontline chemotherapy (98% vs 96%; P =.68), or the incidence of relapsed/refractory disease (40% vs 38%; P =.74). For relapsed/refractory LBCL, similar proportions of patients underwent hematopoietic stem cell transplantation (32% vs 29%; P >.99) or chimeric antigen receptor T‐cell therapy (16% vs 19%; P >.99). Enrollment in clinical trials was comparable (17% vs 14%; P =.64). More than 85% received nurse navigation, but minorities had higher intensity navigation encounters (42% vs 21%; P =.01). The 2‐year OS rates were 81% and 76% for minorities and Whites, respectively (P =.27); the 2‐year PFS rates were 62% and 65%, respectively (P =.78). Conclusions: This study shows similar survival between Whites and minorities with aggressive LBCL, which was likely due to equal access to guideline‐concordant therapy. Minorities received higher intensity navigation encounters, which may have helped them to overcome socioeconomic disadvantages. Although other studies have shown worse outcomes for minorities with aggressive large B‐cell lymphoma, this study demonstrates similar survival in White and minority patients. The authors attribute the equitable outcomes to equal access to guideline‐conforming care and novel treatment options, which may have been attainable by overcoming barriers via the aid of nurse navigation. [ABSTRACT FROM AUTHOR]

Administration of plerixafor with granulocyte‐colony stimulating factor (G‐CSF) mobilizes CD34+ cells much more effectively than G‐CSF alone, but cost generally limits plerixafor use to patients at high risk of insufficient CD34+ cell collection based on low peripheral blood (PB) CD34+ counts following 4 days of G‐CSF. We analyzed costs associated with administering plerixafor to patients with higher day 4 CD34+ cell counts to decrease apheresis days and explored the use of a fixed split dose of plerixafor instead of weight‐based dosing. We analyzed 235 patients with plasma cell disorders or non‐Hodgkin's lymphoma who underwent progenitor cell mobilization and autologous hematopoietic cell transplantation (AHCT) between March 2014 and December 2017. Two hundred ten (89%) received G‐CSF plus Plerixafor and 25 (11%) received G‐CSF alone. Overall, 180 patients (77%) collected in 1 day, 53 (22%) in 2 days and 2 (1%) in 3 days. Based on our data, we present a probabilistic algorithm to identify patients likely to require more than one day of collection using G‐CSF alone. CD34+ cell yield, ANC and platelet recovery were not significantly different between fixed and standard dose plerixafor. Plerixafor enabled collection in 1 day and with estimated savings of $5000, compared to patients who did not receive plerixafor and required collection for three days. While collection and processing costs and patient populations vary among institutions, our results suggest re‐evaluation of current algorithms. [ABSTRACT FROM AUTHOR]

Physicians are encouraged to evaluate MF patients' symptom burdens with the MPN-SAF TSS and to calculate DIPPS-Plus during each clinical encounter, recommended every three months. Myelofibrosis (MF) patients can develop significant symptoms that adversely affect quality of life. A multidisciplinary approach incorporating telemedicine for MF patients provides an effective method to measure patient symptom burdens and to assign prognostic categories. Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. [Extracted from the article]

Background: Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults. Methods: The authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression‐free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value <.01 was considered to be statistically significant a priori. Results: An increase in AHCT was noted in 2017 (28%) compared with 2013 (15%) among patients aged ≥70 years. Although approximately 82% of patients received melphalan (Mel) at a dose of 200 mg/m2 overall, 58% of the patients aged ≥70 years received Mel at a dose of 140 mg/m2. On multivariate analysis, patients aged ≥70 years demonstrated no difference with regard to NRM (hazard ratio [HR] 1.3; 99% confidence interval [99% CI], 1‐1.7 [P =.06]), REL (HR, 1.03; 99% CI, 0.9‐1.1 [P = 0.6]), PFS (HR, 1.06; 99% CI, 1‐1.2 [P = 0.2]), and OS (HR, 1.2; 99% CI, 1‐1.4 [P =.02]) compared with the reference group (those aged 60‐69 years). In patients aged ≥70 years, Mel administered at a dose of 140 mg/m2 was found to be associated with worse outcomes compared with Mel administered at a dose of 200 mg/m2, including day 100 NRM (1% [95% CI, 1%‐2%] vs 0% [95% CI, 0%‐1%]; P =.003]), 2‐year PFS (64% [95% CI, 60%‐67%] vs 69% [95% CI, 66%‐73%]; P =.003), and 2‐year OS (85% [95% CI, 82%‐87%] vs 89% [95% CI, 86%‐91%]; P =.01]), likely representing frailty. Conclusions: The results of the current study demonstrated that AHCT remains an effective consolidation therapy among patients with MM across all age groups. Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy for the management of patients with multiple myeloma, which is a disease of older adults. The results of the current large database study confirm that AHCT remains an effective consolidation therapy in fit older adults aged ≥70 years. [ABSTRACT FROM AUTHOR]

Summary: Transplant‐associated thrombotic microangiopathy (TA‐TMA) is a complication of allogeneic transplantation (allo‐HCT). The incidence and risk factors associated with TA‐TMA are not well known. A retrospective analysis from the Center for International Blood and Marrow Transplant Research (CIBMTR) was conducted including patients receiving allo‐HCT between 2008 and 2016, with the primary objective of evaluating the incidence of TA‐TMA. Secondary objectives included identification of risk factors associated with TA‐TMA, and the impact of TA‐TMA on overall survival and the need for renal replacement therapy (RRT). Among 23,665 allo‐HCT recipients, the 3‐year cumulative incidence of TA‐TMA was 3%. Variables independently‐associated with increased incidence of TA‐TMA included female sex, prior autologous transplant, primary disease (acute lymphoblastic leukaemia and severe aplastic anaemia), donor type (mismatched or unrelated donor), conditioning intensity (myeloablative), GVHD prophylaxis (sirolimus + calcineurin inhibitor), pre‐transplant kidney dysfunction and acute GVHD (time‐varying effect). TA‐TMA was associated with higher mortality (HR = 3·1, 95% Confidence Interval [CI] = 2·8–16·3) and RRT requirement (HR = 7·1, 95% CI = 5·7–311·6). This study provides epidemiologic data on TA‐TMA and its impact on transplant outcomes. Increased awareness of the risk factors will enable providers to be vigilant of this uncommon but serious transplant complication. The results will also provide benchmarking for future study designs and comparisons. [ABSTRACT FROM AUTHOR]

Background: The optimal duration of empiric antimicrobial therapy in febrile neutropenia of unknown origin is unclear. This study evaluated outcomes in autologous and allogeneic hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin who received early de-escalation of broad-spectrum antimicrobials prior to hematopoietic recovery versus those who continued broad-spectrum antimicrobials until hematopoietic recovery. Methods: A single-center, retrospective study assessed hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin. Patients were categorized into either cohort 1, representing early de-escalation prior to hematopoietic recovery, or cohort 2, representing continuation of broad-spectrum antimicrobials until hematopoietic recovery. Results: A total of 107 patients were included (22.4% in cohort 1 and 77.6% in cohort 2). Most patients (87.5%) in cohort 1 underwent haploidentical hematopoietic cell transplantation, whereas 84.3% of patients in cohort 2 received autologous hematopoietic cell transplantation. There were no significant differences in rates of recurrent fever (4.2% versus 7.2%, in cohorts 1 and 2, respectively, adjusted odds ratio = 0.84, P = 0.85), re-escalation (4.2% versus 4.8%, adjusted odds ratio = 1.57, P = 0.64), and Clostridioides difficile -associated infections (4.2% versus 2.4%, adjusted odds ratio = 2.27, P = 0.43). No patient experienced in-hospital mortality, intensive care unit admission, or bacteremia. Conclusion: Hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin in which broad-spectrum antimicrobials were de-escalated prior to hematopoietic recovery did not experience adverse outcomes. These results concur with recently published studies and the Fourth European Conference on Infections in Leukemia guidelines. An early de-escalation approach in haploidentical hematopoietic cell transplantation recipients specifically appears safe and may result in a reduction in antimicrobial utilization. [ABSTRACT FROM AUTHOR]

There is a high risk of voriconazole failure in those with subtherapeutic drug concentrations, which is more common in CYP2C19 (cytochrome P450 2C19) rapid/ultrarapid metabolizers (RMs/UMs). We evaluated CYP2C19 genotype‐guided voriconazole dosing on drug concentrations and clinical outcomes in adult allogeneic hematopoietic cell transplant recipients. Poor (PMs), intermediate (IMs), and normal metabolizers (NMs) received voriconazole 200 mg twice daily; RMs/UMs received 300 mg twice daily. Steady‐state trough concentrations were obtained after 5 days, targeting 1.0–5.5 mg/L. Of 89 evaluable patients, 29% had subtherapeutic concentrations compared with 50% in historical controls (P < 0.001). Zero, 26%, 50%, and 16% of PMs, IMs, NMs, and RMs/UMs were subtherapeutic. Voriconazole success rate was 78% compared with 54% in historical controls (P < 0.001). No patients experienced an invasive fungal infection (IFI). Genotype‐guided dosing resulted in $4,700 estimated per patient savings as compared with simulated controls. CYP2C19 genotype‐guided voriconazole dosing reduced subtherapeutic drug concentrations and effectively prevented IFIs. [ABSTRACT FROM AUTHOR]

Background: Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high-risk group of patients with an expected 5-year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated.Methods: This study compared autologous hematopoietic stem cell transplantation (auto-HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT) as the first transplantation approach for patients with ETF FL (age ≥ 18 years) undergoing auto-HCT or allo-HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression-free survival, relapse, and nonrelapse mortality (NRM).Results: Four hundred forty FL patients had ETF (auto-HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow-up of 69 to 73 months, the adjusted probability of 5-year OS was significantly higher after auto-HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5-year adjusted probability of NRM was significantly lower for auto-HCT (5%) versus MSD (17%) or MUD HCT (33%; P < .0001). The 5-year adjusted probability of disease relapse was lower with MSD (31%) or MUD HCT (23%) versus auto-HCT (58%; P < .0001).Conclusions: Patients with high-risk FL, as defined by ETF, undergoing auto-HCT for FL have low NRM and a promising 5-year OS rate (70%). MSD HCT has lower relapse rates than auto-HCT but similar OS. Cancer 2018;124:2541-51. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Background: Peripheral blood progenitor cell (PBPC) mobilization with chemotherapy in addition to Granulocyte‐Colony Stimulating Factor (G‐CSF) improves cell collection compared to G‐CSF alone; however, it is associated with increased risk of neutropenic fever (NF). Methods: We analyzed risk factors for post‐priming NF and NF association with autologous stem cell transplant outcomes. Between 1998 and 2008, 593 adult patients with lymphoma underwent PBPC mobilization with etoposide and G‐CSF. Results: Median age was 51 years (range 18–77) and 372 (63%) were male. Diagnoses were 457 (77%) non‐Hodgkin lymphoma and 136 (23%) Hodgkin lymphoma. Of 554 (93%) transplanted patients, majority were in complete or partial remission at time of transplant (88%). Overall, 141 (24%) patients were hospitalized for NF. Nine patients (6%) had bacteremia, 4 (3%) had pneumonia, 2 (<1%) had herpes simplex viral infections, and the remaining 126 (90%) had no identified infection source. NF patients had lower likelihood of proceeding to transplant (86% vs. 96%, P < .001), lower CD34+ cell dose collection (median 7.23 × 106 CD34+ cells/kg vs. 8.98 × 106 CD34+ cells/kg, P = .002), and were more likely to require > 4 days of apheresis (48% vs. 37%, P < .001). NF was associated with a higher 30‐day readmission rate following transplant hospitalization (17% vs. 9%, P = .012). Conclusion: NF during etoposide priming is associated with lower likelihood of proceeding to transplant, lower CD34+ cell dose collection, more apheresis days required for collection and a higher 30‐day readmission rate following transplant discharge. [ABSTRACT FROM AUTHOR]

The article discusses a chemoimmunotherapy review for diffuse large B cell lymphoma (DLBCL) patients with hepatic and/or renal dysfunction in 2013-2016. Topics covered include the potential excellent outcomes for such patients if chemoimmunotherapy with appropriated dose adjustments in selected patients is quickly initiated, the possible quick reversal of lymphoma-related organ dysfunction, and the non-dose reduction or withdrawal of cyclophosphamide.

Inhibition of cholesterol synthesis and uptake sensitizes acute myeloid leukaemia ( AML) blasts to chemotherapy. A Phase 1 study demonstrated the safety of high dose pravastatin given with idarubicin and cytarabine in patients with AML and also demonstrated an encouraging response rate. The Southwestern Oncology Group ( SWOG) trial, SWOG S0919, was a Phase 2 trial evaluating the complete remission ( CR) rate in a larger number of patients with relapsed AML treated with idarubicin, cytarabine and pravastatin. This study closed to accrual after meeting the defined criterion for a positive study. Thirty-six patients with a median age of 59 years (range 23-78) were enrolled. The median time from diagnosis to registration was 18 months. Relapse status was first relapse, 17 patients (47%); second relapse, 15 patients (42%); third relapse, two patients (5·5%) and fourth relapse, two patients (5·5%). The response rate was 75% [95% confidence interval: 58-88%; 20 CRs, 7 CR with incomplete count recovery ( CRi)], and the median overall survival was 12 months. The P-value comparing 75-30% (the null response rate based on prior SWOG experience) was 3·356 × 10−4. Given the encouraging CR/ CRi rate, this regimen should be considered for testing in a prospective randomized trial against best conventional therapy. [ABSTRACT FROM AUTHOR]

Inhibition of cholesterol synthesis and uptake sensitizes acute myeloid leukaemia (AML) blasts to chemotherapy. A Phase 1 study demonstrated the safety of high dose pravastatin given with idarubicin and cytarabine in patients with AML and also demonstrated an encouraging response rate. The Southwestern Oncology Group (SWOG) trial, SWOG S0919, was a Phase 2 trial evaluating the complete remission (CR) rate in a larger number of patients with relapsed AML treated with idarubicin, cytarabine and pravastatin. This study closed to accrual after meeting the defined criterion for a positive study. Thirty‐six patients with a median age of 59 years (range 23–78) were enrolled. The median time from diagnosis to registration was 18 months. Relapse status was first relapse, 17 patients (47%); second relapse, 15 patients (42%); third relapse, two patients (5·5%) and fourth relapse, two patients (5·5%). The response rate was 75% [95% confidence interval: 58–88%; 20 CRs, 7 CR with incomplete count recovery (CRi)], and the median overall survival was 12 months. The P‐value comparing 75–30% (the null response rate based on prior SWOG experience) was 3·356 × 10−4. Given the encouraging CR/CRi rate, this regimen should be considered for testing in a prospective randomized trial against best conventional therapy. [ABSTRACT FROM AUTHOR]

Background Exposure to ionizing radiation has been linked to myelodysplastic syndromes (MDS); it is not clear whether therapeutic radiation doses used for prostate cancer pose an increased MDS risk. Methods We performed a retrospective cohort study of prostate cancer patients diagnosed between 1986 and 2011 at Cleveland Clinic, comparing those who underwent definitive treatment with radical prostatectomy (RP) to radio-therapy either external beam radiotherapy (EBRT) or prostate interstitial brachytherapy (PI) and to population- based registries. Competing risk regression analyses were used to determine the cumulative risk of developing MDS. All statistical tests were two-sided. Results Of 10924 patients, 5119 (47%) received radiation (n = 2183 [43%] in EBRT group and n = 2936 [57%] in PI group) and 5805 (53%) were treated with RR Overall, 31 cases of MDS were observed, with age-adjusted incidence rates no higher than in population-based registries. In univariate analyses, advancing age (hazard ratio [HR] = 1.14; 95% confidence interval [CI] -- 1.09 to 1.20; P< .001) and radiotherapy exposure (HR = 3.44; 95% CI = 1.41 to 8.37; P= .007) were statistically significantly associated with development of MDS. In multivariable analyses, although advanced age (HR = 1.13; 95% CI= 1.06 to 1.19; P< .001) remained statistically associated with MDS, radiation did not, although a small non-statistically significant trend existed for PI-treated patients. MDS rates were no higher than in population-based registries. Conclusions With relatively short follow-up, prostate cancer patients definitively treated with radiation did not appear to have a statistically increased risk of subsequent MDS. [ABSTRACT FROM AUTHOR]

Unlabelled: Introduction: Relapse after allogeneic hematopoietic stem cell transplantation in patients with myelodysplasia is a challenging problem with limited treatment options. Attempts to induce a graft-versus-leukemia effect have been used with limited success. In patients with myelodysplasia, sustained complete remissions have generally been limited to patients with long-term remission after transplant and those with low numbers of marrow blasts.Case Presentation: We report the case of a 41-year-old Caucasian woman with relapsed myelodysplastic syndrome and a high blast percentage six months after undergoing an allogeneic transplant who achieved a sustained complete remission after withdrawal of immunosuppression alone.Conclusion: This case highlights the importance of a reasonable period of observation after withdrawing immunosuppression to induce graft-versus-leukemia, and the potential effectiveness of that approach. [ABSTRACT FROM AUTHOR]

Background Constitutive activation of STAT5 (by phosphorylation) has been identified in a number of malignancies, including acute myeloid leukemia ( AML). Objectives We investigated whether the level of phosphorylated STAT5 ( pSTAT5) expression correlates with clinical outcome in AML. Methods Adult patients with newly diagnosed AML receiving induction chemotherapy and with an available diagnostic bone marrow were evaluated. Results Forty-two percent of patients had pSTAT5 expression >0 on immunohistochemical analysis of fixed bone marrow core biopsies. In multivariable analyses, controlling for age, history of antecedent hematologic disorder, cytogenetic risk, and WBC at diagnosis, pSTAT5 expression was significantly associated with an increased risk of death ( HR 1.96, 95% CI 1.19-3.23, P = 0.008) and of relapse after achieving complete remission ( HR 2.31, 95% CI 1.16-4.63, P = 0.018). Conclusions Validation of pSTAT5's prognostic value requires additional study in a larger group of uniformly treated patients. However, our data suggests that targeting this signaling pathway in AML may improve the outcome of patients. [ABSTRACT FROM AUTHOR]

We hypothesized that analysis of single nucleotide polymorphism arrays (SNP-A) and new molecular defects may provide new insight in the pathogenesis of systemic mastocytosis (SM). SNP-A karyotyping was applied to identify recurrent areas of loss of heterozygosity and bidirectional sequencing was performed to evaluate the mutational status of TET2, DNMT3A, ASXL1, EZH2, IDH1/IDH2 and the CBL gene family. Overall survival (OS) was analyzed using the Kaplan-Meier method. We studied a total of 26 patients with SM. In 67% of SM patients, SNP-A karyotyping showed new chromosomal abnormalities including uniparental disomy of 4q and 2p spanning TET2/KIT and DNMT3A. Mutations in TET2, DNMT3A, ASXL1 and CBL were found in 23%, 12%, 12%, and 4% of SM patients, respectively. No mutations were observed in EZH2 and IDH1/IDH2. Significant differences in OS were observed for SM mutated patients grouped based on the presence of combined TET2/ DNMT3A/ASXL1 mutations independent of KIT (P = 0.04) and sole TET2 mutations (P,0.001). In conclusion, TET2, DNMT3A and ASXL1 mutations are also present in mastocytosis and these mutations may affect prognosis, as demonstrated by worse OS in mutated patients. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for patients with acute myeloid leukemia (AML). Our understanding of the biology of leukemic stem cells has continued to improve over the last decade and risk stratification using cytogenetics and molecular markers have improved our ability to select patients who would benefit from allogeneic transplantation. Results of HSCT have also improved substantitally, extending the potential application of allogeneic transplant to more patients. This review discusses the theoretical aspects of transplant, analyzes clinical results, and provides recommendations for the use of HSCT in AML. Further study of the biology of leukemic stem cells and the role for HSCT is necessary to optimize outcomes in AML patients. S TEM C ELLS 2012;30:1581-1586 [ABSTRACT FROM AUTHOR]

Cyclophosphamide is an immunosuppressive agent and an anticancer prodrug which requires bioactivation catalyzed primarily by cytochrome P450 enzymes in order to be transformed into its active alkylating compounds. Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. Herein, we present the case of a chronically ill 21-yearold patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG), and total body irradiation (TBI) followed by an allogeneic hematopoietic stem cell transplant (HSCT) for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. The preparative regimen was tolerated well aside from a hypersensitivity reaction to eATG, and minimal cyclophosphamide-related toxicities. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management. [ABSTRACT FROM AUTHOR]

Early and reliable prediction of the likelihood of achieving adequate stem cell collection for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) would improve collection efficiency, prevent unnecessary aphereses, and permit appropriate treatment alterations. No previous study has reported a threshold CD34+ cell collection quantity on Day 1 or 2 of leukapheresis that could predict successful stem cell collection. We performed a retrospective analysis of all MM patients undergoing first attempt of stem cell collection at our institution from 2001 through 2008. Recursive partitioning analysis was used to identify Day 1 or Day 1+2 CD34+ collection quantity that predicted failure to reach target ≥2 × 106 CD34+ cells/kg within five days of collection. Totally, 172 patients were included in the analysis. Patients underwent mobilization with G-CSF or G-CSF+ chemotherapy. 23 of 172 patients (13.4%) failed to collect sufficient (≥2 × 106 CD34+ cells/kg) CD34+ cells after five days of apheresis: 22 of 29 who collected ≤0.70 × 106 CD34+ cells/kg and 1 of 143 who collected >0.70 × 106 CD34+ cells/kg (75.9% vs. 0.7%, P < 0.001) on Day 1. Collection failure occurred in 23 of 30 patients who collected ≤1.54 × 106 CD34+ cells/kg and 0 of 142 who collected >1.54 × 106 CD34+ cells/kg (76.7% vs. 0%, P < 0.001) on Days 1 + 2. Day 1 CD34+ cell collection quantity identifies patients unlikely to achieve adequate collection for ASCT. Patients who collect ≤0.70 × 106 CD34+ cells/kg on day 1 could be considered for treatment modifications to improve CD34+ collection, such as early administration of plerixafor or large volume apheresis. J. Clin. Apheresis, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone combined with cytarabine and methotrexate) is an intense chemotherapy regimen frequently used for hematologic malignancies including mantle cell lymphoma. To address whether treatment with hyper-CVAD impairs mobilization of peripheral blood stem cells, we retrospectively analyzed mobilization data from 77 consecutive adult patients with mantle cell lymphoma who underwent peripheral blood stem cell (PBSC) mobilization for planned autologous stem cell transplant (ASCT). Compared to patients treated with alternative regimens, patients treated with hyper-CVAD collected fewer CD34++ cells, required more total days of pheresis, and more frequently required a second mobilization attempt, despite being more likely to have undergone mobilization with a VP16-containing regimen. In multivariable linear regression analysis, treatment with hyper-CVAD was associated with a significant reduction in total CD34++ cells mobilized ( p < 0.001). These findings suggest that alternative mobilizing strategies prior to ASCT are needed for patients with mantle cell lymphoma who have received hyper-CVAD. [ABSTRACT FROM AUTHOR]

Prior series have demonstrated that early relapsed (within 1 year) or refractory Hodgkin lymphoma (HL) is associated with poor prognosis. To determine the outcome for patients with early relapsed/refractory HL in the modern era, we combined data from two large transplant centres, Cleveland Clinic Taussig Cancer Institute (CCTCI) and Memorial Sloan-Kettering Cancer Center (MSKCC), and analysed consecutive patients transplanted for relapsed/refractory HL following induction failure or remission durations of <1 year. Two hundred and fourteen patients were analysed and the event-free survival (EFS) and overall survival (OS) at 6 years for all patients were 45% and 55%, respectively. Factors significant for prognosis in multivariate analysis were extranodal disease and bulky disease (≥5 cm). Patients with 0, 1, or 2 risk factors achieved 6 year EFS of 65%, 47%, and 24% and 6 year OS of 81%, 55%, and 27%, respectively. Patients with the sole risk factor of early relapsed/refractory disease achieved good outcomes in this large series; however the presence of bulk and/or extranodal disease significantly reduced EFS and OS. Patients with these additional risk factors are best suited for clinical trials investigating novel salvage regimens and post-transplant maintenance strategies. [ABSTRACT FROM AUTHOR]

High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the preferred treatment modality for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). To assess long-term outcomes of these patients, we retrospectively analysed data from 309 consecutive patients who underwent ASCT for DLBCL between 1994 and 2006. We found that non-relapse mortality (NRM) became the major cause of death beginning approximately 8 years after ASCT. The most common causes of NRM during the study period were respiratory failure (31%), infection (13%), cardiac toxicity (15%) and secondary malignancy (15%). The strongest predictor of relapse mortality (RM) was disease status at transplant: patients who were in second or greater complete or partial remission had a higher risk of RM than those in first complete or partial remission [hazard ratio (HR) 3·7, P < 0·001], as did those who were relapsed or refractory (HR 4·9, P < 0·001). We describe the longest reported follow-up of a large cohort of DLBCL patients uniformly-treated with ASCT. Although relapse was initially the more likely cause of death, NRM exceeded RM after 8 years. After ASCT, surviving patients have significantly increased risk mortality rates relative to the general population and this excess risk persists over time. [ABSTRACT FROM AUTHOR]

The article presents a study regarding the medical case of 16 haemotological malignancy patients. The study uses total body irradiation (TBI), etoposide and antithymocyte globulin (ATG) to conduct multiple unit umbilical cord blood transplantation (MU-UCBT). The result shows that three patients experienced early deaths and one had graft failure but was infused with cryopreserved remission autologous bone marrow and remains alive in complete remission for 1056 days.

Patients with acute myeloid leukemia (AML) with intermediate or high risk cytogenetics are often considered for allogeneic hematopoietic stem cell transplant (AHSCT) in first remission. Between attainment of remission and AHSCT, post-remission chemotherapy is frequently administered, though there is no evidence for its effectiveness. This study was performed to determine the impact of post-remission chemotherapy on outcome after AHSCT. A subset analysis was performed to determine whether the influence of post-remission chemotherapy might be different in those with intermediate compared to high risk cytogenetics. There was no significant difference in relapse mortality (RM) ( p = 0.70), non-relapse mortality (NRM) ( p = 0.12), or survival (OS) ( p = 0.15) between post-remission chemotherapy groups. There was no difference in RM, NRM, or OS between cytogenetic groups according to whether they received post-remission chemotherapy. No differential effect between intermediate and high risk cytogenetics was detected (RM, p = 0.80; NRM, p = 0.23; OS, p = 0.26). These data do not show a benefit of post-remission chemotherapy before AHSCT. [ABSTRACT FROM AUTHOR]

The article discusses a study on the quality of care and clinical outcomes in patients newly diagnosed with acute myeloid leukemia (AML) admitted for remission induction chemotherapy during the weekend as compared to those who were admitted on weekdays. The study included AML patients admitted to the Cleveland Clinic Leukemia Service from 1994 to 2008 for remission induction chemotherapy. It concludes that AML patients admitted in large, teaching referral hospitals on weekend had the same clinical outcomes with patients admitted on weekdays.

The long-term follow-up is presented for 317 patients with acute myeloid leukaemia who underwent human leucocyte antigen-identical sibling marrow transplants between 1984 and 1995 following preparation with busulfan 16 mg/kg and cyclophosphamide 120 mg/kg. Among the 142 (45%) who were alive and leukaemia-free 3 years following transplantation, the leukaemia-free survival at 15 years was 72·8%. The cumulative incidence of late (>3 years beyond transplant) non-relapse mortality at 15 years was 12·9% and of late relapse was 16·5%. None of the variables considered (including age, disease stage, and graft- versus-host disease) were predictive of late failure. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (ASCT) with cyclophosphamide, etoposide and oral busulfan (BuCyVP) is an effective therapy for relapsed or refractory non-Hodgkin lymphoma (NHL). Substituting intravenous for oral busulfan reduces variability in drug exposure, potentially improving the safety and efficacy of the BuCyVP regimen. We retrospectively compared the outcomes of 604 consecutively treated patients who underwent ASCT for NHL with BuCyVP using oral ( n = 468) or IV ( n = 136) busulfan, without measurement of busulfan levels for pharmacokinetic (PK) analysis. Patients who received oral busulfan experienced more severe oral mucositis and a higher incidence of nonrelapse mortality. Median overall survival (OS) after ASCT was 72 months with oral busulfan but was not reached for the IV busulfan group. IV busulfan was associated with a lower rate of relapse, and superior relapse-free survival (RFS) and OS. In multivariate models, the route of busulfan administration was an independent prognostic factor for relapse ( P = 0·01), RFS ( P = 0·002) and OS ( P = 0·001). IV busulfan appears to provide better efficacy and lower toxicity than oral busulfan in ASCT with BuCyVP for NHL. Whether PK-based busulfan dosing can achieve further improvements in this setting is worthy of study. [ABSTRACT FROM AUTHOR]

Elevated pretransplant serum ferritin levels have been associated with an increased incidence of morbidity and mortality after allogeneic haematopoietic stem cell transplantation (HCT). We studied 222 patients who underwent myeloablative allogeneic HCT in whom pretransplantation serum ferritin levels were available. Pretransplantation ferritin > 1910 μg/l was associated with lower overall survival ( P = 0·003), lower relapse-free survival ( P = 0·003), decreased chronic graft- versus-host disease (GVHD) ( P = 0·019) and increased non-relapse mortality (NRM) ( P = 0·042). Similar results were obtained when pretransplantation ferritin was analysed as a continuous variable and by quartiles. Our results indicate that an elevated pretransplant ferritin level adversely impacts transplantation outcomes. The adverse impact of elevated ferritin on NRM and survival was despite its association with lower incidences of acute and chronic GVHD, which are major causes of NRM. The association of ferritin with iron overload and its influence on HCT outcomes requires further prospective validation. [ABSTRACT FROM AUTHOR]

The outcome of patients with acute lymphoblastic leukemia (ALL) in first relapse is poor. We retrospectively evaluated patients with ALL in first relapse, 18-60 years of age, to define a prognostic score. For all patients, a scoring system of 0-3 was developed with 1 point for each of the following: age at diagnosis ≥45 years, lactate dehydrogenase (LDH) at the time of relapse ≥1.5 times upper limits of normal (ULN), not proceeding to allogeneic bone marrow transplant (BMT). A similar scoring system was developed for patients proceeding to BMT. LDH ≥1.5 times ULN at the time of relapse predicted poor overall survival. Patients with a prognostic score of greater than 1 have a poor prognosis, even with BMT, and should be considered for treatment with innovative approaches such as Phase 1 clinical trials. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation provides the most powerful antileukemic effect in the treatment of acute myeloid leukemia. Due to its significant morbidity and mortality, it should be used in first remission patients whose relapse risk is substantial. Reduced intensity transplantation is safer and extends the application of early transplantation to older patients and those with comorbidities. In patients with advanced disease, allotransplantation provides a lower chance for cure, but is often the only curative treatment available. Advances in histocompatibility typing and supportive care have improved results of allogeneic transplantation in acute myeloid leukemia. [ABSTRACT FROM AUTHOR]

Summary. We evaluated transplant-related mortality (TRM), leukaemia relapse, leukaemia-free survival (LFS) and overall survival (OS) in patients receiving busulphan and cyclophosphamide (BuCy) or cyclophosphamide and total body irradiation (CyTBI) prior to allogeneic bone marrow transplantation (BMT) for acute myelogenous leukaemia (AML) in first remission. Outcomes of 381 human leucocyte antigen (HLA)-matched sibling transplants using BuCy were compared with 200 transplants using CyTBI performed between 1988 and 1996. The incidence of hepatic veno-occlusive disease was higher with BuCy (13%) than with CyTBI (6%) (P = 0·009). Risks of acute and chronic GVHD were similar. In multivariate analysis, relapse risk was higher in the BuCy group [relative risk (RR) = 1·72; 95% confidence interval (CI), 1·05–2·81; P = 0·031]. Eleven of 373 evaluable patients in the BuCy group had a central nervous system relapse in contrast to none of 194 evaluable patients in the CyTBI group (P = 0·016). There were no differences in TRM, LFS and OS. CyTBI conditioning may lower relapse risk but produces comparable TRM, LFS and OS to BuCy for HLA-matched sibling transplantation in first remission AML. [ABSTRACT FROM AUTHOR]

Mezlocillin and carbenicillin were administered intravenously to healthy male volunteers, for six days each, in a double-blind crossover study. Tests to detect abnormalities in haemostasis were performed before, during and after administration. Platelet aggregation studies indicated that both antibiotics interfered with platelet aggregation and secretion resulting in prolonged bleeding times. The effect was dose related and rapidly reversible after discontinuation of the antibiotics. It always occurred earlier and was more profound with carbenicillin than with mezlocillin (P=0.008). Bleeding times > 15 min were observed in 17% of volunteers who received 18 g/day of mezlocillin and 83% of volunteers who received 18 g/day of carbenicillin (P < 0.05). There were no abnormalities in the coagulation cascade. The risk of acquiring an antibiotic-induced clinical bleeding disorder is lower with mezlocillin than with carbenicillin. [ABSTRACT FROM PUBLISHER]

One hundred fifty-six hospitalized adult patients treated with ticarcillin, piperacillin, mezlocillin, or cefotaxime (control) wereprospectively observed for determination of frequencies of platelet dysfuntion and bleeding. Increases in bleeding times (⩾5 min above pretreatment values) occurred in 73% of patients receiving ticarcillin, 43% receiving piperacillin, 25% receiving mezlocillin, and 17% receiving cefotaxime (P < .0001); chemotherapy, thrombocytopenia, age of ⩾60 years, dose of ⩾12 g per day, and duration of treatment of six or more days were significant covariables. Significant bleeding occurred in 34% of patients treated with ticarcillin, 17% with piperacillin, 2% with mezlocillin, and 5% with cefotaxime (P = .0005); chemotherapy, thrombocytopenia, primary marrow disorders affecting platelet function, prolonged prothrombin time, and azotemia were significant covariables. Bleeding was associated with an elevated pretreatment bleeding time, an increase in bleeding time during treatment, and the maximal observed bleeding time during treatment (P < .0001). [ABSTRACT FROM PUBLISHER]

A letter to the editor on granulocyte stimulating-colony factor-associated splenic artery rupture is presented.