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Recently there has been a growing interest in evaluating body composition as a marker for prognosis in cancer patients. The association of body composition parameters and outcomes has not been deeply investigated in patients with autologous hematopoietic stem cell transplantation (HSCT) recipients with non-Hodgkin lymphoma (NHL). We conducted a retrospective cohort study of 264 NHL patients who received autologous HSCT. PreHSCT abdominal CT scans at the levels of L3 were assessed for body composition measures. We evaluated sarcopenia, myosteatosis, high visceral adipose tissue (VAT) and high visceral adipose tissue density (VATD). Using multivariable Cox proportional regression, we analyzed the association of clinical and transplant-related characteristics with overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM). In a multivariate regression model, patients with higher VATD had worse OS (HR 1.78; 95% confidence intervals CI 1.08-2.95, p = 0.02) and worse NRM (HR 2.31 95% CI 1.08-4.95, p = 0.02) than with lower VATD. Patients with lower levels of VAT also had worse RFS (HR 1.49 95% CI 1.03-2.15, p = 0.03). Sarcopenia and myosteatosis were not associated with outcomes. High pre-transplant VATD was associated with lower OS and higher NRM, and low pre-transplant VAT was associated with worse RFS in patients with NHL undergoing autologous HSCT., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Using the National Cancer Database, we identified 10,290 patients with newly diagnosed mantle cell lymphoma (MCL) treated with chemotherapy with or without upfront autologous stem cell transplantation (ASCT). Only 17% of patients underwent ASCT. Patients who underwent ASCT were younger and more likely to have lower comorbidity scores, private insurance, higher income and education, and treatment received at an academic facility. On multivariable analysis, age, comorbidity index, insurance type, the transition of care, facility type, distance to facility, and diagnosis year were predictive for ASCT use. ASCT use was associated with improved 5-year overall survival in younger (82% vs. 64%, p  < .001) and older (70% vs. 40%, p  < .001) patients, which was retained in the matched propensity score and 12-month analyses. Female gender, the diagnosis year ≥2009, private insurance, higher income, and education were associated with superior survival, whereas Black race and higher comorbidities predicted inferior survival.

Objective/background: Relapse is the most common cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT). No standard of care exists, and a wide range of treatments are used for post-alloHCT relapse. In the recent era, several novel therapies including targeted agents are available for acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS)., Methods: We reviewed outcomes after alloHCT relapse, with or without use of these newer agents for ALL, AML, and MDS. In total, 115 adults with relapsed or refractory ALL (n = 17), AML (n = 67), and MDS (n = 31) at median 5 (range, 1-64) months after their first alloHCT in 2010-2018 were included., Results: Median follow-up was 19 (range, 6-80) months after relapse from alloHCT. Targeted agents were given to 29 (25%) patients. In multivariable analysis, use of targeted agent at any time point after relapse was not associated with survival. Matched unrelated (vs. matched sibling; hazard ratio [HR] 1.70; p = .027) or haploidentical donor grafts (vs. matched sibling; HR 2.69; p = .003), presence of grade II-IV acute graft-versus-host disease before relapse (HR 2.46; p < .001), and less than 12 months from HCT to relapse (<6 vs. > 12 months; HR 6.34; p < .001; 6-12 vs. > 12 months; HR 3.16; p = .005) were adverse prognostic factors for post-relapse survival., Conclusion: Outcomes after alloHCT relapse remain poor regardless of the novel agent use. Innovative treatment strategies are needed to improve outcomes after relapse post-alloHCT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

Natural killer (NK) cells are regulated by killer immunoglobulin-like receptor (KIR) interactions with human leukocyte antigen class I ligands. Various models of NK cell alloreactivity have been associated with outcomes after allogeneic hematopoietic cell transplant (alloHCT), but results have varied widely. We hypothesized that somatic mutations in acute myeloid leukemia (AML) in the context of KIR profiles may further refine their association with transplant outcomes. In this single-center, retrospective, observational study, 81 AML patients who underwent matched-related donor alloHCT were included. Post-HCT outcomes were assessed based on mutational status and KIR profiles with the Kaplan-Meier method and log-rank test. On multivariable analysis those with any somatic mutations and C1/C2 heterozygosity had less acute graft-versus-host disease (GvHD) (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.14-0.75; P = .009), more relapse (HR, 3.02; 95% CI, 1.30-7.01; P = .010), inferior relapse-free survival (RFS; HR, 2.22; 95% CI, 1.17-4.20; P = .014), and overall survival (OS; HR, 2.21; 95% CI, 1.17-4.20; P = .015), whereas those with a missing KIR ligand had superior RFS (HR, 0.53; 95% CI, 0.30-0.94; P = .031). The presence of a somatic mutation and donor haplotype A was also associated with less acute GvHD (HR, 0.38; 95% CI, 0.16-0.92; P = .032), more relapse (HR, 2.72; 95% CI, 1.13-6.52; P = .025), inferior RFS (HR, 2.11; 95% CI, 1.07-4.14; P = .030), and OS (HR, 2.20; 95% CI, 1.11-4.38; P = .024). Enhanced NK cell alloreactivity from more KIR activating signals (donor B haplotype) and fewer inhibitory signals (recipient missing KIR ligand or C1 or C2 homozygosity) may help mitigate the adverse prognosis associated with some AML somatic mutations. These results may have implications for improving patient risk stratification prior to transplant and optimizing donor selection., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objective/background: Busulfan/cyclophosphamide (Bu/Cy) and busulfan/fludarabine (Bu/Flu) are both standard myeloablative conditioning (MAC) regimens for allogeneic hematopoietic cell transplantation (alloHCT). We compared the effectiveness of these regimens with a focus on quality of life (QOL)., Methods: This was a single center, retrospective analysis of adult acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients who underwent a first T-cell replete HLA-8/8 matched related or unrelated donor alloHCT. Patients received a myeloablative regimen of either parenteral Bu/Cy or Bu/Flu. Outcomes assessed included infections, graft-versus-host-disease (GVHD), relapse, relapse mortality (RM), relapse-free survival (RFS), nonrelapse mortality (NRM), overall survival (OS), and QOL., Results: From 2008 to 2017, 126 AML and 84 MDS adult patients age ≥18 years were identified meeting inclusion criteria. In terms of QOL, there were no significant differences between Bu/Cy and Bu/Flu cohorts in the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) scores or mucositis severity for either AML or MDS patients. Amongst AML patients, those receiving Bu/Flu had more rapid neutrophil and platelet recovery and a shorter length of hospital stay (LOS); there were no differences in the other posttransplant outcomes. Similarly, amongst MDS patients, those receiving Bu/Flu had more rapid platelet recovery and a shorter LOS as well as more CMV infections, but less NRM and no differences in other outcomes., Conclusion: We confirmed that myeloablative Bu/Flu conditioning has comparable clinical and QOL outcomes to Bu/Cy., (Copyright © 2019 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

Objective/background: Cytomegalovirus (CMV) infection and disease are common infectious complications after allogeneic hematopoietic cell transplantation (alloHCT). Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is a ligand of the natural killer (NKG2D) receptor on immune effector cells that helps mediate NK cell alloreactivity. We hypothesized that MICA polymorphisms may influence CMV infection and disease incidence after alloHCT., Methods: We conducted a retrospective analysis of 423 adults at the Cleveland Clinic with hematologic malignancies treated with a matched related or unrelated donor alloHCT. CMV cases analyzed included a compositive of instances of viral copy replication above detection limits as well as any biopsy-proven tissue invasive disease episodes. Genotypes at the MICA-129 position have been categorized as weak (valine/valine; V/V), intermediate (methionine/valine; M/V), or strong (methionine/methionine; M/M) receptor affinity., Results: In multivariable analysis, V/V donor MICA-129 genotype was associated with CMV infection and disease (hazard ratio [HR] = 1.40; 95% confidence interval [CI], 1.00-1.96; p = .05), but not MICA mismatch (HR = 1.38; 95% CI, 0.83-2.29; p = .22). There was no association of acute or chronic GVHD with MICA donor-recipient mismatch (HR = 1.05; 95% 95% CI, 0.66-1.68; p = .83 and HR = 0.94; 95% CI, 0.51-1.76; p = .85, respectively) or V/V donor MICA-129 genotypes (HR = 1.02; 95% CI, 0.79-1.31; p = .89 and HR = 0.89; 95% CI, 0.65-1.22; p = .47, respectively)., Conclusion: These findings suggest that the donor MICA-129 V/V genotype with weak NKG2D receptor binding affinity is associated with an increased risk of CMV infection and disease after alloHCT., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to report., (Copyright © 2019 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

Optimal administration of busulfan (Bu) is hampered by variable and unpredictable drug metabolism in individual patients. At our institution, Bu was previously administered with fixed weight-based dosing (WBD) in combination with cyclophosphamide (Cy) and etoposide (E) for patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT). In 2014, we adopted real-time pharmacokinetic (PK)-guided therapeutic drug monitoring (TDM) of Bu for all NHL patients undergoing Bu-containing ASCT. Here we compare outcomes of NHL patients who underwent ASCT with Bu/Cy/E using WBD and those who did so using TDM of Bu. We studied 336 consecutive adult NHL patients who underwent ASCT with Bu/Cy/E using WBD from January 2007 to December 2013 (n = 258) or TDM from May 2014 to December 2017 (n = 78), excluding patients with mantle cell lymphoma. Clinical outcomes, including relapse, nonrelapse mortality (NRM), progression-free survival (PFS), and overall survival (OS), hepatotoxicity and pulmonary toxicity were compared in the 2 groups. To adjust for differences in baseline characteristics between the groups, propensity-matched cohorts of WBD and TDM patients were also studied. After the first dose of Bu, the dose was increased in 36% of the patients and decreased in 41%. Changes in pulmonary and liver function from baseline to transplantation were not different between the 2 groups, although these changes showed significantly less variability with TDM than with WBD. Relapse was significantly lower and PFS was improved with TDM; 2-year estimates were 19% for TDM and 38% for WBD for relapse (P = .004) and 69% and 55%, respectively, for PFS (P = .038). No significant between-group differences in NRM or OS were seen. In multivariable analysis, TDM remained prognostic for lower risk of relapse (hazard ratio [HR], .52; 95% confidence interval [CI], .30 to .89; P = .018), but did not remain prognostic for PFS (HR, .74; 95% CI, .48 to 1.16; P = .19). Propensity-matched cohorts displayed similar patterns of outcomes. In subset analysis based on disease status at ASCT, TDM was associated with less relapse and better PFS than WBD for patients who underwent transplantation in less than complete remission (CR) compared with those who underwent transplantation in CR. Compared with WBD, PK-directed TDM of Bu reduces the incidence of relapse when used in combination with Cy and E for patients with NHL undergoing ASCT, particularly for patients in less than CR. These data support the continued use of personalized PK-guided dosing for all NHL patients undergoing ASCT with Bu-containing preparative regimens., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Autologous hematopoietic cell transplantation (AHCT) is standard therapy for patients with chemosensitive, relapsed, diffuse large B cell lymphoma (DLBCL). We performed a retrospective cohort study to delineate subsequent (conditional) and relative survival in 371 adult patients with DLBCL who underwent AHCT between 2000 and 2014 and had survived for 1, 2, 3, or 5 years after transplant. The probability of overall survival at 10 years after AHCT was 62%, 71%, 77%, and 86%, respectively, for the 4 cohorts, whereas that of progression-free survival (PFS) was 55%, 65%, 72%, and 81%, respectively. The respective cumulative incidence of nonrelapse mortality (NRM) at 10 years after transplantation was 13%, 12%, 11%, and 8%, respectively. In multivariable analysis, older age was associated with greater mortality risk among all but 5-year survivors; relapse within the landmark time was associated with greater mortality risk in all groups. Older age and relapse within the landmark time were associated with worse PFS in all groups. Standardized mortality ratio (SMR) was significantly higher than an age-, gender-, and race-matched general population, with the magnitude of SMR decreasing as the landmark time increased (4.0 for 1-year, 3.0 for 2-year, 2.4 for 3-year, and 1.8 for 5-year survivors). Our study provides information on long-term survival and prognosis that will assist in counseling patients with DLBCL who have received AHCT. Survival improves with longer time in remission post-transplant, although patients continue to remain at risk for NRM, underscoring the need for continued vigilance and prevention of late complications., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Obesity has implications for hematopoietic progenitor cell (HPC) mobilization, chemotherapy administration, and medication dosing. We analyzed the impact of obesity on HPC mobilization as well as key outcomes that are associated with cell dose in autologous hematopoietic cell transplantation (AHCT) recipients., Methods: We conducted a retrospective cohort study on 556 consecutive eligible AHCT recipients at our institution from 1/2004 to 12/2009. Patients were categorized into four groups based on the body mass index (BMI): underweight (BMI < 18.5), normal (18.5-24.9), overweight (25.0-29.9), or obese (≥30.0). Primary endpoints of interest included HPC mobilization, neutrophil and platelet recovery, hospital stay and survival., Results: The diagnoses were mostly non-Hodgkin lymphoma, multiple myeloma, and Hodgkin lymphoma. The majority of the patients had received three or less prior chemotherapy regimens and had not received prior radiation therapy. Most patients had chemosensitive disease at time of transplant. For HPC mobilization regimen, 68% received chemotherapy and G-CSF, 32% received G-CSF alone. Busuflan/etoposide/cyclophosphamide, melphalan, and busulfan/cyclophosphamide were used for conditioning. Obesity did not correlate with HPC mobilization and had no association with neutrophil or platelet recovery, or length of transplant hospitalization. On multivariable analysis, obese patients demonstrated better survival than those who were not obese., Conclusion: Obese AHCT recipients had similar rates of HPC mobilization, neutrophil and platelet engraftment and length of transplant hospitalization, and experienced better survival compared with recipients with lower BMI. High BMI by itself should not be considered as a contraindication to AHCT., (© 2019 Wiley Periodicals, Inc.)

Background: The spectrum of infectious complications in autologous hematopoietic cell transplant recipients (AHCT) with multiple myeloma has not been well described in the recent era of novel agent induction and improved supportive care., Methods: We conducted a retrospective cohort study of 413 adult myeloma AHCT recipients at our institution from 2007-2016 to describe the cumulative incidence and risk factors for various infections and FN occurring within the first 100 days after AHCT. Additionally, landmark analysis was done among 404 patients who survived at least 100 days after transplant admission to estimate the association of infections with subsequent non-relapse mortality (NRM), overall survival (OS), and relapse-free survival (RFS)., Results: Cumulative incidences (95% CI) of infection events by day 100 were: FN 43% (38-48), any infection 21% (17-25), bacterial 17% (14-21), viral 4% (3-7) and fungal 1% (0.5-3), central line-associated blood stream infection 3% (2-6), and Clostridium difficile colitis 6% (4-8). Patients with infection had a longer initial transplant hospitalization (median 17 vs 16 days, P < 0.01), more readmissions (31% vs 8%, P < 0.01), and spent more days in hospital in first 100 days (median 18 vs 16 days, P < 0.01). A 100-day mortality was low and similar between groups (2% vs 1%, P = 0.28). In landmark analysis of 404 100-day survivors, OS was worse among patients with early infections (hazard ratio 1.54 [1.03-2.30], P = 0.03), although there was no difference in NRM and RFS., Conclusions: Notwithstanding advances in supportive care, early infectious complications remain a relevant source of morbidity and require attention in myeloma AHCT recipients., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (AHSCT) is a standard of care for patients with relapsed Hodgkin lymphoma. Different conditioning regimens before AHSCT have been used, with the 2 most common being BEAM (carmustine, etoposide, cytarabine, and melphalan) and BUCYVP16 (busulfan, cyclophosphamide, and etoposide). We retrospectively compared the outcomes of patients treated with BEAM (n = 128) or BUCYVP16 (n = 105) followed by AHSCT. After a median follow-up of 4.2 years for BEAM and 3.8 for BUCYVP16 from AHSCT, the 5-year cumulative incidence of relapse was 29% with BEAM compared with 56% with BUCYVP16 (P < .001). Median progression free survival (PFS) and overall survival (OS) were not reached with BEAM and were 2.0 and 7.8 years with BUCYVP16, respectively. Improved PFS (P < .001) and OS (P = .001) were observed with BEAM for patients who needed transplant within 24 months from diagnosis and for patients not in complete remission (non-CR; P = .001 and P < .001, respectively) at AHSCT. In this large retrospective comparison the use of BEAM conditioning before AHSCT resulted in a statistically significant improved PFS and OS and lower relapse compared with BUCYVP16. This supports the use of BEAM as a frontline conditioning regimen before AHSCT for early relapsed and non-CR Hodgkin lymphoma., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Donor-derived T-cells mediate graft-versus-leukemia effect, immune reconstitution, and graft-versus-host-disease (GvHD) after allogeneic hematopoietic cell transplantation (HCT). We examined the association of donor cell subsets with outcomes in recipients of myeloablative allogeneic HCT using bone marrow (BM, N = 359) grafts from 2002 to 2014 with related or unrelated donors. Analysis considered pre-infusion graft total nucleated cell (TNC), CD34+ CD3+, CD4+, CD8+ doses. Most patients received busulfan-cyclophosphamide or etoposide-total body irradiation conditioning for acute leukemia or myelodysplastic syndrome. Calcineurin inhibitor-mycophenolate mofetil (CNI-MMF) (49%) or calcineurin inhibitor-methotrexate (CNI-MTX) (47%) were used for GvHD prophylaxis. In multivariable analysis, higher CD34+ dose was associated with platelet engraftment (P < 0.001) and lymphocyte recovery (P = 0.006). There was no association of donor cell subsets with donor chimerism or overall survival. In conclusion, BM graft composition is associated with myeloablative allogeneic HCT outcomes and future studies to evaluate optimal graft composition are needed.

Pre-transplant PET/CT may be prognostic in diffuse large B-cell lymphoma (DLBCL) patients undergoing autologous stem cell transplantation (ASCT). We reviewed relapsed and pre-transplant PET/CT scans of 32 patients with DLBCL treated with ASCT to determine the Deauville score and the maximum standardized uptake value (SUV max ). Patients with a Deauville score of 4 had a significantly inferior prognosis. The 3-year progression-free survival (PFS) for patients with Deauville 1-3 score was 64%, compared to 0% for Deauville 4, while the 3-year overall survival (OS) was 84% and 25%, respectively (p < .001, p = .002). The change in the SUV max (>66 versus ≤66%) was not predictive of PFS or OS, but a high pre-transplant SUV max (>6) demonstrated a trend towards an inferior PFS. Pre-transplant PET/CT is a tool for identifying DLBCL patients at high risk for treatment failure with ASCT and could be used to risk-stratify patients in prospective clinical trials of novel transplant strategies.

Although day +100 survival among allogeneic hematopoietic cell transplantation (HCT) recipients has improved over time, longer-term survival remains a challenge. The aim of this study was to identify prognostic factors for survival among patients surviving longer than 100 days using baseline characteristics and factors identified within the first 100 days after transplantation. Of 413 patients undergoing a first allogeneic HCT between 2006 and 2014, 335 survived >100 days post-transplantation. The majority underwent a myeloablative transplantation (75%) with a bone marrow (BM) (52%) graft source. One-year all-cause mortality (ACM) was 29%, with 16% relapse mortality (RM) and 12% nonrelapse mortality. In multivariable analysis, high-risk disease (hazard ratio [HR], 1.55; P = .003), non-cytomegalovirus infection (HR, 1.79; P = .003), more days hospitalized (HR, 1.16; P < .001), and relapse (HR, 4.38; P < .001) within the first 100 days were associated with increased risk of ACM. Patients with higher income (HR, .89; P = .024) and those who received BM (HR, .52; P < .001) or umbilical cord blood (HR, .40; P = .002) relative to peripheral blood stem cells had lower risk of ACM. Our study identifies risk factors for adverse long-term survival in 100-day survivors, a time point when patients frequently are discharged from transplantation centers. In addition to disease- and transplantation-related factors, low socioeconomic status was associated with worse long-term survival, highlighting the need for focused efforts to improve outcomes in vulnerable patient populations., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Young fit patients with mantle cell lymphoma (MCL) are commonly treated with induction chemotherapy followed by high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT). Induction regimens with modifications of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and/or incorporation of high-dose cytarabine (HDAC) appear more effective than R-CHOP alone., Patients and Methods: We adopted a modification of the Nordic protocol using standard, rather than higher dose R-CHOP, alternating with HDAC (rituximab plus HDAC), for 3 cycles each or, for patients already treated with R-CHOP alone before referral for AHCT, an additional 2 cycles of rituximab plus HDAC. We herein report our experience with 28 patients treated with this regimen who proceeded to AHCT, and compare their outcomes with patients treated with either standard-dose R-CHOP (n = 38) or R-HCVAD/MA (cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate, and cytarabine; n = 21), before AHCT., Results: With a median follow-up duration of 26 months, our data show that this modification of the Nordic regimen is a highly effective pre-AHCT first-line therapy for MCL (3-year progression-free and overall survival rates of 69% and 75%, respectively)., Conclusion: By using a less intense induction, this regimen can serve as a platform for combined use of novel agents, with less risk of additive toxicity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is frequently performed in patients with hematologic malignancies. ASCT can result in significant nausea, pain, and discomfort. Supportive care has improved, and pharmacologic therapies are frequently used, but with limitations. Music has been demonstrated to improve nausea and pain in patients undergoing chemotherapy, but little data are available regarding the effects of music therapy in the transplantation setting. In a prospective study, patients with lymphoma or multiple myeloma undergoing ASCT were randomized to receive either interactive music therapy with a board-certified music therapist or no music therapy. The music therapy arm received 2 music therapy sessions on days +1 and +5. Primary outcomes were perception of pain and nausea measured on a visual analog scale. Secondary outcomes were narcotic pain medication use from day -1 to day +5 and impact of ASCT on patient mood as assessed by Profile of Mood States (POMS) on day +5. Eighty-two patients were enrolled, with 37 in the music therapy arm and 45 in the no music therapy arm. Patients who received MT had slightly increased nausea by day +7 compared with the no music therapy patients. The music therapy and no music therapy patients had similar pain scores; however, the patients who received music therapy used significantly less narcotic pain medication (median, 24 mg versus 73 mg; P = .038). Music therapy may be a viable nonpharmacologic method of pain management for patients undergoing ASCT; the music therapy patients required significantly fewer morphine equivalent doses compared with the no music therapy patients. Additional research is needed to better understand the effects of music therapy on patient-perceived symptoms, such as pain and nausea., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

High-dose busulfan (Bu) is an integral component of commonly used preparative regimens for both allogeneic and autologous transplantation. There is significant interest in comparing the efficacy and toxicity of administering Bu every 6 (Bu6) or every 24 hours (daily Bu). To facilitate a therapeutic dose-monitoring protocol, we transitioned from Bu6 to daily Bu dosing for patients with Hodgkin and non-Hodgkin lymphoma undergoing autologous stem cell transplantation (ASCT). Here, we retrospectively review outcomes of 400 consecutive eligible lymphoma patients who underwent ASCT from 2007 to 2013 with high-dose busulfan (Bu), cyclophosphamide (Cy), and etoposide (E). Bu was given at a fixed dose of either .8 mg/kg every 6 hours for 14 doses for 307 patients or a fixed dose of 2.8 mg/kg every 24 hours for 4 doses (days -9 through -6) for 93 patients who underwent transplantation after the transition from Bu6 to daily Bu was made. Toxicity was assessed using pulmonary and liver function tests (LFT) at specified time points before and after ASCT. Baseline patient and disease characteristics of patients dosed with Bu6 and daily Bu were similar. There was no significant difference in forced expiratory volume in 1 second or diffusing capacity of the lungs for carbon monoxide before and after transplantation in the Bu6 versus daily Bu cohorts. Changes in LFTs with daily Bu were not significantly different than those with Bu6. There were no differences in relapse, nonrelapse mortality, progression-free survival, or overall survival between Bu6 and Bu 24 administration schedules in univariable or multivariable analysis (P ≥ .34). For a subset of 23 patients who had first-dose Bu levels measured, we observed significant variation in an median estimated cumulative area under the curve (AUC) of 17,568 µM-minute (range, 12,104 µM-23,084 µM-minute). In conclusion, daily Bu with Cy/E is more convenient than Bu6, has equivalent outcomes, and results in no increase in either hepatic or pulmonary toxicity. Consistent with previous reports, there is a significant range of Bu AUC levels, with a standard deviation of 13%. These data provide rationale for our prospective clinical trial of real-time therapeutic dose monitoring of Bu., (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Autologous hematopoietic cell transplantation (AHCT) is standard therapy for eligible patients with multiple myeloma. Health care disparities can influence transplantation outcomes. However, the association of socioeconomic status (SES), a major indicator of health care disparities, with outcomes in patients with myeloma after AHCT has not been previously described. We analyzed 346 consecutive AHCT recipients with myeloma who underwent transplantation between 2003 and 2013 in this retrospective cohort study. Zip code of residence at the time of AHCT was obtained to assess annual household income based on 2010 US census data (median, $49,054; range, $16,546 to $127,313). SES groups were divided into < $45,000 (low; n = 120), $45,000 to $60,000 (middle; n = 116), and > $60,000 (high; n = 110). The low-income cohort had smallest portion of Caucasians (69% versus 89% versus 91%); otherwise, patient, disease, and transplantation characteristics were comparable among cohorts or different without significant patterns found. Median follow-up was 49 months. There was no difference among SES groups in overall survival, progression-free survival, nonrelapse mortality, or relapse in univariate and multivariable analysis. Similarly, SES was not associated with survival in a subset analysis of 303 patients who had survived for 1 year after transplantation., (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective/background: The most common indication for high-dose chemotherapy (HDC) and autologous hematopoietic cell transplantation (AHCT) in the 1990s was breast cancer. Several randomized trials and a more recent meta-analysis failed to show a survival benefit for AHCT in metastatic breast cancer (MBC); however, they demonstrated a better-than-expected 10-year to 15-year survival in 5-15% of patients. We thus evaluated the long-term results of treatment with HDC and AHCT in MBC at our institution., Methods: From 1984 to 2000, 285 patients underwent AHCT for MBC. The patient characteristics were collected through the Cleveland Clinic, United Transplant Database. A retrospective review of the medical records of the long-term surviving breast-cancer patients treated with HDC and AHCT was conducted., Results: With a median follow-up of 169 months, 34 (12%) remain alive. Of the 251 patients who died, 218 (87%) died of metastatic disease. A comparison by age (<50 years and >50 years) and hormonal status did not demonstrate any differences in relapse (p=.33 and p=.32, respectively) or survival (p=.13 and p=.42). Of the 34 long-term survivors, sufficient data were available on 28 patients, and further evaluation revealed that the majority had a primary or locally recurrent oligometastatic disease., Conclusion: This retrospective evaluation of patients who underwent AHCT for MBC demonstrates long-term survival in a small subset of patients, primarily those with primary or recurrent oligometastatic disease. Oligometastatic breast cancer is a distinct entity within MBC, which may be curable with multimodality therapy. We thus conclude there remains no overall-survival benefit to HDC in MBC., (Copyright © 2015. Published by Elsevier B.V.)

Chronic graft-versus-host disease (cGVHD) is one of the main late complications of allogeneic hematopoietic stem cell transplant and a major contributor to the mortality and morbidity in surviving recipients. Skin is the most common involved organ in cGVHD and may mimic a wide spectrum of dermatological conditions in its clinical and histopathologic manifestations. Some of the commonly simulated diseases are scleroderma, morphea, and lichen sclerosus. Chronic GVHD simulating eosinophilic fasciitis (EF) is relatively rare, frequently presenting with skin induration, a typical "peau d'orange" appearance, peripheral blood eosinophilia, myalgia, arthralgia, and arthritis leading to joint contractures in severe cases.Diagnosis is based on clinical manifestations and histopathology. Treatment is challenging because most cases are refractory to first-line therapy of glucocorticoids and calcineurin inhibitors (CNIs), and there is no standard second-line therapy.We report a comprehensive review of literature on all reported cases of CGVHD presenting as EF. We also describe an additional interesting case of cGVHD presenting as EF that was resistant to traditional therapy of high-dose glucocorticoids and cyclosporin A, but showed complete resolution of skin manifestations after addition of imatinib.Chronic GVHD presenting as EF is a rare variant of sclerodermatous cGVHD. Diagnosis is difficult, and treatment of cGVHD mimicking EF remains a therapeutic challenge because of obscure pathogenesis and poor response to traditional immunosuppressive medications. Emerging insights into the pathogenesis of cGVHD have resulted in the development of novel targeted therapies, which may improve outcomes and should be attempted in this subset of the disease. Larger studies are warranted to substantiate these preliminary findings.

The clinical relevance of mismatches at the MHC class I-related chain A (MICA) in hematopoietic stem cell transplantation (HSCT) remains unclear. We investigated the association of MICA donor/recipient mismatch and whether there is an interaction between these and HLA-DPB1 mismatch on clinical outcomes after unrelated donor HSCT. Our study included 227 patients who underwent unrelated donor allogeneic HSCT at our institution between 2000 and 2010. Among these, 177 (78%) received HSCT from a 10/10 HLA-matched donor. MICA genotyping was performed using commercially available kits. In univariable analysis, the risk of grade II to IV acute graft-versus-host disease (GVHD) was greater for patients with MICA mismatch (hazard ratio [HR], 1.73; P = .02) than for those with HLA-DPB1 mismatch (HR, 1.62; P = .07). When MICA and HLA-DPB1 were assessed simultaneously, patients mismatched at both loci had the greatest risk (HR, 2.51; P < .01) and those mismatched at only 1 locus had somewhat greater risk (HR, 1.53; P = .12) than patients matched at both loci; this remained significant in multivariable analysis. The 100-day incidence was 66%, 45%, and 31%, respectively (P = .03). Results were similar for grade III and IV acute GVHD, with 100-day incidence 34%, 16%, and 8% (P = .01). These results are clinically pertinent to donor selection strategies and indicate that patients with mismatch at both MICA and HLA-DPB1 are at increased risk for acute GVHD., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Patient readmission within 30 days from discharge has been perceived by the Centers for Medicare and Medical Services as an indicator of poor healthcare quality for specific high-cost medical conditions. Patients who undergo allogeneic hematopoietic cell transplantation (allo-HCT) are often being readmitted. Our study identified the risk factors for 30-day readmission among 618 adult recipients of myeloablative allo-HCT from 1990 to 2009. Two hundred forty-two (39%) of 618 patients (median age = 42 years [range: 18-66]) were readmitted a median of 10 days (range: 1-30) from their hospital discharge. Median duration of readmission was 8 days (range: 0-103). Infections (n = 68), fever with or without identified source of infection (n = 63), gastrointestinal complications (n = 44), graft-versus-host disease (GVHD) (n = 38), and other reasons (n = 29) accounted for 28%, 26%, 18%, 16%, and 12% of readmissions, respectively. During their index admission, patients who were subsequently readmitted had more documented infections (P < .001), higher hematopoietic cell transplantation comorbidity index (HCT-CI) (P < .01), total body irridiation (TBI)-based conditioning (P < .001), unrelated donor (P < .001), and peripheral stem cell (P = .014) transplantation. In multivariable analysis, HCT-CI (odds ratio [OR] = 1.78; 95% confidence interval [CI], 1.25-2.52), TBI-based preparative regimen (OR = 2.63; 95% CI, 1.67-4.13), and infection during admission for allo-HSCT (OR = 2.00; 95% CI, 1.37-2.92) predicted 30-day readmission. Thirty-day readmission itself was an independent predictor of all-cause mortality (hazard ratio [HR](Adj) = 1.66; 95% CI, 1.36-2.10). Our data emphasize the importance of a risk-standardized approach to 30-day hospital readmission if it is used as a quality-of-care metric for bone marrow transplantation., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Vitamin D (VD) deficiency can cause osteomalacia, bone pain, muscle weakness, fatigue, and increased risk of fracture, and may precipitate or exacerbate osteopenia and osteoporosis. Patients receiving treatment for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) may have limited exposure to sunlight and often experience gastrointestinal side effects that may decrease their ability to maintain an adequate VD level. We hypothesized that patients with AML and ALL would have a low VD level after allogeneic hematopoietic cell transplant (HCT), and that these patients would have a high incidence of osteoporosis/osteopenia. We therefore studied the incidence of low VD level and low bone mineral density after HCT. Of 289 patients with AML or ALL undergoing HCT between January 1, 2000, and January 31, 2009, at the Cleveland Clinic, 58 (20.1%) patients had VD testing after HCT. Of these, 52 (89.7%) patients had a low VD level, and 6 (10.3%) had a normal level. Most patients with VD testing had graft-versus-host disease (GVHD) and were taking corticosteroids (94.8% and 98.3%, respectively). Of the 49 patients with VD testing who also had bone mineral density testing, 65% had abnormal (low bone density) results. Only 21% of patients with VD testing were taking VD supplements prior to testing, and 65% had an elevated parathyroid hormone level. We found that most patients did not have VD testing after HCT, but those that did were very likely to have a low level and have low bone mineral density. Those with a low VD level were likely to have received corticosteroids, have GVHD, and have an elevated parathyroid hormone (PTH) level. Given the potential morbidity of low VD level, VD deficiency should be considered after HCT. Prospective study of VD level and its impact on morbidity and mortality after HCT is warranted., (2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

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., (© 2011 Blackwell Publishing Ltd.)

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., (© 2011 Blackwell Publishing Ltd.)

Allogeneic hematopoietic stem cell transplantation (SCT) for patients who have previously undergone allogeneic or autologous SCT is potentially curative, but dangerous. To identify patient, disease, and treatment characteristics associated with outcome, we analyzed prognostic factors in 98 consecutive patients who underwent second transplants using allogeneic donors at the Cleveland Clinic between May 1987 and October 2008. Inclusion criteria included age ≥18 years, first SCT either autologous or allogeneic, and second SCT allogeneic. Patients whose second transplant was myeloablative (MA) had shorter survival (median 3.2 versus 14.7 months, P < .001) than patients whose second transplant was nonmyeloablative (NMA). In multivariable analysis, MA second transplant was associated with a higher risk of NRM (hazard ratio [HR] 2.01, P = 0.022) and death (HR 2.13, P = 0.002). Improved survival after NMA second transplant occurred primarily in patients without acute leukemia and when the first transplant was allogeneic. Among 17 patients transplanted within 3 months of first transplant, mortality was 100% and median survival was 2.3 months. MA transplantation within 3 months of prior SCT carries an unacceptably high rate of NRM. NMA second transplants were associated with substantially less NRM and despite a higher incidence of relapse, significantly improved survival compared to MA second transplants., (Copyright © 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

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.

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.

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 microg/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.

Cytogenetic analysis at the time of diagnosis predicts outcome in patients with acute myelogenous leukemia (AML). For those patients with favorable risk cytogenetics, stem cell transplant can be delayed until the time of relapse. For those patients with nonfavorable cytogenetic risk profiles, stem cell transplant may be required for optimal survival benefit. We treated patients with de novo AML and age less than 60 years first with etoposide, mitoxantrone, cytarabine, and G-CSF (EMA-G) to induce remission. Patients in complete remission were assigned to treatment with chemotherapy alone if they had favorable risk cytogenetics defined as the identification of a core-binding factor translocation. Patients with any other cytogenetic profile were assigned to treatment with either autologous or allogeneic stem cell transplant depending on the availability of an HLA-matched donor. Following EMA-G, 33 of 40 patients (83%) achieved CR. Of the 25 patients who actually were treated with postremission chemotherapy, 21 were treated with their assigned risk-adapted therapy. Of the 33 patients in remission, 5 year relapse-free survival (RFS) and overall survival (OS) was 46 and 38%, respectively. Our intensive and risk-adapted, stem cell transplant approach to the treatment of patients with AML requires a better definition of risk and does not appear to substantially improve results compared with more standard approaches., (Copyright 2008 Wiley-Liss, Inc.)

Elevated serum ferritin is associated with reduced survival following allogeneic transplantation and an increased risk of toxic and infectious complications after autologous hematopoietic stem cell transplantation (ASCT). We studied 315 patients who underwent ASCT for Hodgkin (HL) or non-Hodgkin lymphoma (NHL) at our institution in whom pretransplantation ferritin was available to determine its association with survival. On multivariate analysis, a pretransplantation ferritin>685 ng/mL was associated with significantly lower overall (OS; P=.002) and relapse-free survival (RFS; P=.021). Ferritin>685 ng/mL was associated with a higher incidence of relapse (P=.005) and relapse mortality (P<.001), but not of nonrelapse mortality (NRM; P=.23). Similar results were seen when pretransplantation ferritin was analyzed as a continuous variable and by quartiles. Our results indicate the need for studies designed to correlate an elevated ferritin with iron overload and to analyze the benefit of strategies to reduce the extent of iron overload.

Results were analyzed for 48 consecutive patients with acute myeloid leukemia not in remission who underwent unrelated donor bone marrow or stem cell transplantation between 1991 and February 2003 at 2 transplant centers. Forty-six were adults with a median age of 32 years (range, 4-58 years). Forty-two were HLA-A, -B, and -DR matched with their respective donors, and 6 were mismatched at 1 of these loci. The conditioning regimen was myeloablative in all cases: busulfan/cyclophosphamide/etoposide in 34 patients, busulfan/cyclophosphamide in 10 patients, and total body irradiation based in 4 patients. Median follow-up for survivors was 540 days (range, 145-2716 days). Only patients with <5000 peripheral blood blasts per microliter at the time of transplantation survived 2 years (18% versus 0%; P = .003). Similarly, patients with <20% blasts in the marrow at the time of transplantation had superior 2-year survival compared with those who had > or =20% (33% versus 5%; P = .04). Patients with <20% blasts who had > or =3 prior therapies also fared poorly. Cause of death was more commonly treatment related rather than relapse related. This study confirms that patients with acute myeloid leukemia not in remission can achieve prolonged survival with myeloablative conditioning and unrelated donor cell transplantation. However, sustained survival occurs only in patients with a low disease burden at the time of unrelated donor stem cell transplantation, and patients with a high disease burden may benefit from added counseling regarding the high risk of death due to both treatment-related toxicities and disease relapse.

Data on real-world outcomes of axicabtagene ciloleucel (axi-cel) therapy for relapsed/refractory large B-cell lymphoma (R/R LBCL) are limited. In this intent to treat (ITT) analysis, we reviewed records of 38 consecutive patients with R/R LBCL for whom axi-cel was intended. Twenty-seven (71%) patients received axi-cel and 11 (29%) did not. Patients in the non-axi-cel group had a higher hematopoietic cell transplantation comorbidity index (HCT-CI) (median 4 vs. 2, p =.04). Median overall survival for the ITT, axi-cel and non-axi-cel group was 10 (95% CI, 3.7 to 13), 13 (95% CI, 7.7 to N.R.) and 1 (95% CI, 0.4 to 3.7) month(s) respectively. Factors limiting axi-cel use were disease progression, sepsis, manufacturing failure and socioeconomic barrier in 6 (55%), 3 (27%), 1 (9%) and 1 (9%) patient(s) respectively. Additional strategies are needed to ensure all LBCL patients for whom chimeric antigen receptor (CAR) T-cell therapy is prescribed can receive this treatment. [ABSTRACT FROM AUTHOR]

Busulfan (Bu) based conditioning regimens are associated with serious toxicities including myelosuppression, hepatotoxicity, and sinusoidal obstructive syndrome (SOS). Previous literature reports increased risk of toxicities when the daily AUC concentrations exceed 6000 uM-minute. Bu TDM has also been associated with improved overall and progression free survival in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. We implemented real time pharmacokinetic (PK)-guided therapeutic dose monitoring (TDM) of Bu for myeloablative conditioning (MAC) regimens. Compare toxicity of IV Bu before and after implementation of TDM. The primary endpoint was incidence of hepatotoxicity, defined as days of elevation of AST or ALT > 3 times the upper limit of normal (ULN) or total bilirubin >1.5 times ULN. Secondary outcomes included time to neutrophil and platelet engraftment, duration of IV opioid administration, breakthrough antiemetic use, incidence of SOS, hospital length of stay (LOS), incidence of Bu dose adjustment, and repeat Bu PK. A Bu PK-guided TDM program was implemented in April 2018 for patients receiving busulfan/ cyclophosphamide (BuCy) MAC regimens for allo-HSCT. Medical records were retrospectively reviewed with weight-based dose (WBD) BuCy conditioning from August 2017 through March 2018 (N=14) and TDM from April 2018 through December 2018 (N=22). Bu was given at a fixed dose of 0.8 mg/kg/dose every 6 hours for 16 doses on days -8 to -4 for WBD patients. For TDM patients, after a WBD of 3.2 mg/kg/dose on day -7 (Bu 1), serial plasma Bu concentrations were used to calculate Bu area under the curve (AUC) for subsequent dose adjustment on days -6 to -4 to target a daily AUC of 5000 μM-minute. If the AUC actual /AUC target exceeded 1.2 or was less than 0.8, the second dose of Bu (Bu 2) was changed by no more than ± 20%, repeat PK samples were drawn, and the process was repeated for TDM for the third dose of Bu. Recipients of Bu TDM were younger than those receiving WBD (median 45 vs. 58 years, p=0.008). No other baseline differences were observed. There was no difference in hepatotoxicity between TDM and WBD (median 1 vs. 0 days, p=0.40), time to neutrophil (median 17 vs. 17 days, P=0.18) or platelet engraftment (median 29 vs. 25 days, p=0.75), IV opioid administration (median 4 vs. 4 days, p=0.83), breakthrough antiemetic use (median 59 vs. 58 doses, p=0.99), SOS (4.5 vs. 7.1%, p=1.0), or LOS (median 28 vs. 27 days, p=0.95). In the TDM group, 45% of patients had increases and 41% had decreases in Bu dose after Bu 1. 32% of patients required repeat PK after Bu 2. A PK dose monitoring program for MAC IV Bu regimens may be considered a safe practice in allo-HSCT recipients. The majority of patients receiving PK-guided TDM required dose changes, and TDM patients had no significant difference in toxicity compared to those receiving WBD. [ABSTRACT FROM AUTHOR]

Advances in allogeneic hematopoietic cell transplantation (HCT) have led to significantly improved day 100 survival over time. Longer-term (≥1 year) survival, however, has not changed significantly. In an effort to improve outcomes and identify patients (pts) at higher risk for 1-year mortality, we created a day 100 risk assessment tool. The Day 100 Risk Assessment tool includes 11 items: HCT-co-morbidity index, distance from transplant center, performance status (PS) at day 100, GVHD requiring systemic corticosteroids, infection requiring intravenous antimicrobials, caregiver support, poor coping skills/motivation, substance abuse, poor health literacy/access, medication compliance, and "other" concerns from the care team. Pts were given a point for each identified factor and categorized as low risk (score 0-2) or high risk (score≥3). High risk pts were targeted for closer follow up beyond 100 days. Cox regression was used to identify risk factors for overall survival (OS) within the first year after HCT. Between 11/2015-6/2018, 208 pts underwent allogeneic HCT and 161 pts survived without relapse at day 100 (Table). Median follow up is 12 months (range 3-33). 1-year OS for low-risk pts was significantly better than for high-risk pts (82% vs 68%, P=0.006; Figure). Multivariable analysis accounting for both pre-transplant and Day 100 risk factors identified older age (≥55), (HR 2.92, 95% CI 1.21-7.08, P=0.017); high disease risk (HR 2.93, 95% CI 1.34-6.39, P=0.007), and day 100 high-risk score (HR 2.29, 95% CI 1.17-4.48, P=0.015) as significant factors for poor OS. Univariate analysis of individual components of the day 100 risk score identified poor PS at day 100, infection, and caregiving concerns as significant variables, P<0.004. A second multivariable model including individual factors demonstrated that poor PS (HR 2.68, P=0.013), infection (HR 2.57, P=0.009) and older age (HR 2.55, P=0.041) remained significantly associated with poor OS. In sum, we developed a Day 100 Risk Assessment tool and identified factors occurring within the first 100 days beyond traditional pre-transplant variables which significantly impact longer-term outcome. Targeted close follow up of these higher risk pts may help to improve survival of this at-risk population. [ABSTRACT FROM AUTHOR]

Background Relapse is a challenge after allogeneic hematopoietic cell transplantation (alloHCT) in MDS. MHC class I chain-related gene A (MICA) is a ligand of the natural killer (NKG2D) receptor on immune effector cells. There have been conflicting reports in regards to MICA mismatch and relapse after alloHCT in hematologic malignancies (Carapito Blood 2016, Askar BBMT 2017). However, these studies did not assess somatic mutations, which have shown to impact relapse (Coleman NEJM 2017). We first assessed risk factors for relapse within 6 and 12 months after alloHCT. We then assessed for an effect of somatic mutations and MICA dimorphisms on relapse. Methods We conducted a single center, retrospective analysis of adults with MDS who underwent 1st alloHCT with T-cell replete HLA-8/8 matched related (MRD) or unrelated donor (MUD). In addition to cytogenetic risk stratification, a subset of patients had a 36-gene somatic mutation panel assessed prior to alloHCT by next-generation sequencing. Dimorphisms of MICA-129 were categorized as weak (valine/valine; V/V), intermediate (methionine/valine; M/V), or strong (methionine/methionine; M/M) receptor affinity. Results From 2000 - 2017, 128 adult MDS patients met inclusion criteria. Median age at alloHCT was 56 years (range, 20-76). IPSS-R scores at diagnosis included 2% very good, 42% good, 23% intermediate, 19% poor, and 14% very poor risk. 62% had MUDs and 87% had a myeloablative regimen. Among 78 patients with data, donor/recipient MICA mismatch was present in 8% while donor MICA-129 dimorphisms were 49% V/V, 42% M/V, and 9% M/M In multivariable analysis, the presence of at least 1 of these less favorable mutations (ASXL1, DNMT3A, FLT3, KRAS, NRAS , and TP53) was a risk factor for relapse within 6 mos (HR 4.30, CI 1.40-13.3, P=0.011; Figure 1); 6-mo relapse incidence (CI) was 45% (22-65) for those with at least 1 of the above mutations vs. 15% (9-22) for all others. A MRD graft was a risk factor for relapse within 12 mos (HR 2.27, CI 1.12-4.59, P=0.023); 12-mo relapse incidence was 36% (23-50) for those with a MRD vs. 19% (11-28) for MUDs. In a 41-patient subset with both MICA and mutation data, although not significant, patients with both donor V/V dimorphism and at least 1 of these less favorable somatic mutations had higher relapse incidence (40% at 12 mos) than those with only 1 of these adverse factors (28%) or neither factor (9%) (P=0.12; Figure 2). Conclusion The presence of at least 1 of the 6 less favorable somatic mutations in our cohort was associated with a risk of relapse within 6 mos after alloHCT for MDS. Our data suggest an additive effect of both weak NK cell activation and less favorable somatic mutations in increasing the risk of relapse, but was not statistically significant. Future investigation of larger cohorts and mechanistic studies are needed to better assess potential interactions between these two elements and the risk of relapse. [ABSTRACT FROM AUTHOR]

Background BuCyVP and BEAM are two commonly used conditioning regimens for AHCT. Previous literature has reported improved outcomes with BEAM compared to BuCyVP in Hodgkin lymphoma (HL) patients, although results in non-Hodgkin lymphoma (NHL) patients are scarce but similar. Our institution switched from using BuCyVP to BEAM as AHCT conditioning for HL in 2016. We conducted a retrospective study to evaluate tolerability and resource utilization with the two regimens. Given limited data and comparable outcomes, this may influence decisions to use one regimen over the other in patients with NHL. Objectives Assess resource utilization and toxicity of BEAM vs. BuCyVP in patients undergoing AHCT for HL. The primary endpoint was hospital length of stay (LOS). Secondary outcomes were 30-day readmission rates, incidence of fever, time to neutrophil and platelet engraftment, incidence of transfer to intensive care unit (ICU), time on intravenous (IV) opioids, and incidence of diuretic and breakthrough antiemetic use. Methods Beginning March 2016, BEAM replaced BuCyVP as the standard conditioning regimen for AHCT for HL at our institution. We retrospectively reviewed medical records of HL patients receiving BuCyVP with pharmacokinetic (PK)-guided therapeutic dose monitoring (TDM) of busulfan from October 2014 through March 2016 (N = 19) and BEAM from April 2016 through September 2017 (N = 18). Results BuCyVP recipients had significantly longer average hospital LOS, relative to both admission date (21 vs. 19 days, p < 0.001) and transplant date (12 vs. 11 days, p = 0.028), increased incidence of fever (89.5% vs. 33.3%, p < 0.001), increased average days of IV opioid administration (8 vs. 1, p < 0.001), and increased average number of doses of furosemide (3 vs. 0, p < 0.001). BuCyVP resulted in shorter average days to platelet engraftment compared to BEAM (17 vs. 20, p = 0.021). No patients were re-admitted to the hospital within 30 days of discharge in either group. There was no difference in average time to neutrophil engraftment (10 vs. 10 days, p = 0.22), average number of breakthrough antiemetic doses (89 vs. 102, p = 0.17), or incidence of transfer to an ICU (10.5% vs. 0%, p = 0.49) between groups. Conclusions Compared to BuCyVP, patients receiving BEAM as conditioning for AHCT for HL had significantly shorter hospital LOS, fewer episodes of fevers and required less IV opioids and furosemide. However, there was no difference in other endpoints evaluated (e.g., neutrophil engraftment, ICU transfer and breakthrough antiemetic use). Our study provides the background information on expected resource utilization and toxicities for the two regimens and will assist in decisions regarding use of these regimens in NHL patients where outcomes between the two are comparable [ABSTRACT FROM AUTHOR]

Pharmacists are increasingly identified as vital members of the HSCT multidisciplinary team. At our institution, pharmacists recently established roles providing clinical pharmacy services in the outpatient setting focused on performing interventions during the pre-HSCT clinic visit. The primary objective was to evaluate the number of medication discrepancies identified during pre-HSCT clinic visits performed by pharmacists, defined as addition, removal, or dose adjustment of current medications. Secondary objectives were to evaluate the number of interventions made by pharmacists for drug interactions, chemotherapy dose adjustments, and other medication recommendations for all patients prior to HSCT. A retrospective review of all patients admitted for HSCT from August 2018 to 2019 was performed. Patients are seen by their HSCT provider about 1 week prior to HSCT. At this visit, oncology trained pharmacists specializing in HSCT meet with the patient and provide services such as medication reconciliation, screening for drug interactions, screening for pertinent medication allergies/ intolerances and identifying alternatives, assessing medication adherence, evaluating need for chemotherapy dose adjustments, and identifying barriers to medication access. Patients that are unable to be seen by the pharmacist receive extensive chart review prior to admission to identify medication interventions. HSCT pharmacists performed 150 pre-HSCT clinic visits for 88 (59%) autologous, 46 (31%) allogeneic, and 16 (11%) Chimeric Antigen Receptor Therapy (CAR- T) recipients. A total of 511 medication discrepancies were identified in 128 (85%) patients seen (Figure 1). In addition to the 150 patients seen, 88 patient charts were reviewed by a pharmacist. A total of 66 significant drug interactions requiring intervention were identified in 52 (22%) patients and 30 chemotherapy dose adjustments were implemented in 29 (12%) patients. Other medication recommendations were made to the provider for 109 (46%) patients. Examples of these interventions include stopping oral chemotherapy prior to HSCT, modifying supportive care medications to reflect patient preference and prior response, modifying hydration due to cardiac history, coordinating steroid tapers before haploidentical HSCT or CAR-T, adjusting prophylactic antimicrobials due to allergies or to meet institutional standards, coordinating refills, and developing a plan for non-formulary medications. Pharmacists play a crucial role in providing safe and effective care to HSCT patients, and their involvement in the multidisciplinary team can lead to significant clinical interventions. Future directions include expansion of the role of HSCT pharmacists through Pharmacy Consult Agreements, focusing on HSCT patients post-transplant and within a Survivorship Clinic. [ABSTRACT FROM AUTHOR]

Background ES is a potential complication following AHCT. First-line treatment typically involves corticosteroids (CS). In 2002, due to historically high ES incidence resulting in prolonged hospitalizations requiring CS treatment, our institution adopted the practice of administering prophylactic CS in patients undergoing AHCT. Due to lack of contemporary evidence supporting ES prophylaxis as well as potential intolerance of prophylactic CS noted in our patient population, a pilot was instituted to remove prophylactic CS from MEL conditioning regimen for multiple myeloma (MM) or amyloidosis. Objectives The primary objective was to evaluate the impact of prophylactic CS on the incidence of ES. Secondary objectives included hospital length of stay (LOS), duration of intravenous (IV) opioid administration during hospitalization, and incidence of infection, fever, or 30-day readmission due to any cause. Methods Beginning December 2016, CS for ES prophylaxis were removed from our standard of care in patients receiving MEL. Prior to this pilot, patients received methylprednisolone 40 mg IV daily from day +5 to day +15 or hospital discharge (whichever occurred sooner). We retrospectively reviewed the charts of patients receiving MEL from June 1 to December 15 of 2016 (CS group) and December 16, 2016 to June 30, 2017 (CS-free group). ES was defined as noninfectious fever >38°C and new documented rash at the time of engraftment (between day +7 to +11). Results A total of 76 patients were reviewed (CS group, n = 40; CS-free group, n = 36). Baseline characteristics were similar between groups in terms of median age (63 vs. 63 years, p =.65), sex (62.5% vs. 56% male, p =.54), and median CD34+ cell dose (6.36 vs. 6.43 × 106 cells/kg, p =.75). There was no difference in the incidence of documented ES between the CS and CS-free groups (2.5% vs. 0%, p = 1.00). There were no significant differences in median hospital LOS (14 vs. 14 days, p =.67), incidence of infection (17.5% vs. 22.2%, p =.61), incidence of fever (25% vs. 25%, p =.81), and 30-day readmission rate (17.5% vs. 11.1%, p =.43) in CS vs. CS-free groups, respectively. Patients in the CS group received significantly more days of IV opioid administration (median 4.5 vs. 4.0, p =.01). A greater proportion of patients received treatment with CS for suspected ES in the CS-free group compared to the CS group (8.3% vs. 2.5%, p =.34), possibly due to the strict conditions required for our definition of ES or the preemptive use of CS. Conclusions These results suggest a low overall incidence of ES in MM or amyloidosis patients undergoing AHCT using MEL. The use of prophylactic CS did not have a significant impact on incidence of ES which could be attributed to the pre-specified definition of ES. A preemptive strategy of using CS in patients with suspected ES may be sufficient in ameliorating symptoms associated with this syndrome. [ABSTRACT FROM AUTHOR]