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The combination of hypomethylating agents with the selective Bcl-2 inhibitor venetoclax (HMA-VEN) has emerged as a highly active regimen in patients with acute myelogenous leukemia (AML) in both the upfront and relapsed/refractory (r/r) settings. We report our early experience with a cohort of patients who were able to proceed to allogeneic hematopoietic cell transplantation (alloHCT) after HMA-VEN therapy. Thirty-two patients with AML (19 r/r and 13 de novo) with a median age of 62 years underwent alloHCT after HMA-VEN therapy. Twenty-two (68.8%) were in complete remission (CR)/CR with incomplete count recovery at time of HCT. With a median follow up of 14.4 months, the 1-year overall survival (OS) was 62.5%, and disease-free survival was 43.8%. The 1-year nonrelapse mortality rate was 18.8%, and the cumulative incidence of relapse was 37.5%. Among patients who underwent alloHCT in CR, the 1-year OS was 77.3%, and the cumulative incidence of nonrelapse mortality was 9.1%. The cumulative incidence of grade II-IV acute graft-versus-host disease was 43.8%. We conclude that alloHCT after HMA-VEN is therapy associated with favorable allogeneic HCT outcomes in newly diagnosed older patients with AML, as well as those with r/r AML., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Acute lymphoblastic leukemia (ALL) is associated with poor survival in older adults, and allogeneic hematopoietic cell transplant (HCT) with reduced-intensity conditioning (RIC) has been an increasingly used strategy in this population. At City of Hope we conducted a retrospective analysis of 72 patients who underwent allogeneic HCT with fludarabine and melphalan (FluMel) as the conditioning regimen between 2005 and 2018, from either a matched sibling or fully matched unrelated donor while in complete remission. Tacrolimus and sirolimus (T/S) were used as graft-versus-host disease (GVHD) prophylaxis. Overall survival and progression-free survival at 4 years post-HCT were 58% and 44%, respectively. The cumulative incidences of relapse/progression and nonrelapse mortality at 4 years were 34% and 22%, respectively. Patients with Philadelphia chromosome-positive (Ph+) ALL had a significantly lower cumulative incidence of relapse/progression (20% versus 48% for patients with Ph-negative status, P = .007). In conclusion, RIC HCT with FluMel conditioning and T/S GVHD prophylaxis was associated with favorable outcomes in patients with Ph+ ALL and should be considered as a viable consolidative therapy for adult patients with ALL., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Historically, outcomes of adult patients with relapsed acute lymphoblastic leukemia (ALL) who fail to enter remission with conventional chemotherapy are very poor. Blinatumomab, a bispecific CD3/CD19 antibody, has shown remarkable activity in relapsed/refractory (r/r) ALL. Although allogeneic hematopoietic cell transplant (HCT) is the recommended consolidation therapy for patients with r/r ALL who respond to salvage therapy, HCT and toxicity outcomes for those who received blinatumomab salvage and HCT remain largely unknown. We treated 89 patients with r/r ALL with blinatumomab, of whom 43 patients (48%) achieved remission. Here we describe our single-center experience in the subset of patients who responded to blinatumomab salvage therapy for eradication of either gross (n = 24) or minimal residual disease (n = 11) before HCT. Overall survival at 1 and 2 years after allogeneic HCT was 77% and 52%, respectively. Leukemia-free survival at 1 and 2 years were 65% and 40%, respectively. Additionally, with blinatumomab administration pre-HCT, no unusual toxicities such as delayed neutrophil/platelet engraftment or graft failure were observed. Acute grades II to IV graft-versus-host disease (GVHD) at day +100 post-HCT was at 43% and 2-year chronic GVHD was 36%, both comparable with historic control subjects. Finally, results of our subset analysis based on pre-HCT minimal residual disease (MRD) status indicated no significant difference in survival outcomes among patients undergoing transplant in MRD-negative status and the entire cohort. In conclusion, based on results of this study, blinatumomab may be considered as a safe and effective agent for r/r ALL patients before HCT., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Cyclophosphamide (Cy)/etoposide combined with fractionated total body irradiation (FTBI) or i.v. busulfan (Bu) has been the main conditioning regimens for allogeneic hematopoietic cell transplantation (alloHCT) for young patients with acute myelogenous leukemia (AML) eligible for a myeloablative conditioning (MAC) regimen. Recent data has suggested that i.v. Bu could be the preferred myeloablative regimen in patients with myeloid malignancies. However, Bu-based regimens are associated with higher rates of sinusoidal obstruction syndrome. Here we report long-term survival outcomes of patients with AML receiving FTBI combined with Cy or etoposide before undergoing alloHCT at City of Hope (COH). We obtained a retrospective review of a prospectively maintained institutional registry of clinical outcomes in 167 patients (median age, 41 years; range, 18 to 57 years) with AML in first or second complete remission who underwent alloHCT at COH between 2005 and 2015. Eligible patients received a MAC regimen with FTBI (1320 cGy) and Cy (120 mg/kg) for unrelated donor transplantation or etoposide (60 mg/kg) for related donor transplantation. Graft-versus-host disease (GVHD) prophylaxis was provided with tacrolimus and sirolimus. In this retrospective study, 6-year overall survival was 60% and nonrelapse mortality was 15%. The GRFS rate was 45% at 1 year and 39% at 2 years. We also describe late metabolic effects and report the cumulative incidence of secondary malignancies (9.5%). Overall, in this young adult patient population, our results compare favorably to chemotherapy-based (i.v. Bu) conditioning regimens without significant long-term toxicity arising from TBI-based regimens., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The current standard of care for patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) is high-dose conditioning followed by autologous stem cell transplantation (ASCT). For some patients (ie, those with highest-risk disease, insufficient stem cell numbers after mobilization, or bone marrow involvement) allogeneic hematopoietic cell transplantation (alloHCT) offers the potential for cure. However, the majority of patients undergoing alloHCT receive reduced-intensity conditioning as a preparative regimen, and studies assessing outcomes of patients after alloHCT with myeloablative conditioning are limited. In this retrospective study, we reviewed outcomes of 22 patients with recurrent and refractory NHL who underwent alloHCT with myeloablative BEAM conditioning and received tacrolimus/sirolimus as graft-versus-host disease (GVHD) prophylaxis at City of Hope between 2005 and 2018. With a median follow-up of 2.6 years (range, 1.0 to 11.2 years), the probabilities of 2-year overall survival and event-free survival were 58.3% (95% confidence interval [CI], 35.0% to 75.8%) and 45.5% (95% CI, 24.4% to 64.3%), respectively. The cumulative incidence of grade II to IV acute GVHD was 45.5% (95% CI, 23.8% to 64.9%), with only 1 patient developing grade IV acute GVHD. However, chronic GVHD was seen in 55% of the patients (n = 12). Of the 22 eligible patients, 2 had undergone previous ASCT and 2 had undergone previous alloHCT. Both patients with previous ASCT developed severe regimen-related toxicity. Patients who underwent alloHCT with chemorefractory disease had lower survival rates, with 1-year OS and EFS of 44.4% and 33.0%, respectively. In conclusion, alloHCT with a BEAM preparative regimen and tacrolimus/sirolimus-based GVHD should be considered as an alternative option for patients with highest-risk lymphoma whose outcomes are expectedly poor after ASCT., (Copyright © 2018. Published by Elsevier Inc.)

Allogeneic hematopoietic stem cell transplantation (alloHCT) is offered increasingly to elderly patients with hematologic malignancies. However, outcome data in those who are 70 years or older are limited, and no standard conditioning regimen has been established for this population. In this retrospective study we evaluated the outcome of 53 consecutive patients aged 70 years and older who underwent alloHCT with melphalan-based reduced-intensity conditioning (RIC) at City of Hope. Engraftment was prompt, with median time to neutrophil engraftment of 15 days. More than 95% of patients achieved complete donor chimerism within 6 weeks from HCT, consistent with the "semiablative" nature of this regimen. With a median follow-up of 31.1 months, the 2-year overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM) were 68.9%, 63.8%, and 17.0%, respectively. Cumulative incidence of relapse at 1 and 2 years was 17.0% and 19.3%, respectively. One hundred-day cumulative incidence of grades II to IV acute graft-versus-host disease was 37.7% (grades III to IV, 18.9%), and 2-year cumulative incidence of chronic graft-versus-host disease was 61.9% (extensive, 45.9%). The only significant predictor for poor OS was high/very high disease risk index. Transplant-related complications and morbidities observed here did not differ from the commonly expected in younger patients treated with RIC. In conclusion, alloHCT with a melphalan-based conditioning regimen is associated with acceptable toxicities and NRM, lower incidence of relapse, and favorable OS and PFS in patients aged 70 years or older., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Allogeneic hematopoietic cell transplantation (HCT) is recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (CR) and high-risk patients in first CR. Given its relative rarity, data on outcomes of HCT for T-ALL are limited. We conducted a multicenter retrospective cohort study using data from 208 adult patients who underwent HCT between 2000 and 2014 to describe outcomes of allogeneic HCT for T-ALL in the contemporary era. The median age at HCT was 37 years, and the majority of patients underwent HCT in CR, using total body irradiation (TBI)-based myeloablative conditioning regimens. One-quarter of the patients underwent alternative donor HCT using a mismatched, umbilical cord blood, or haploidentical donor. With a median follow up of 38 months, overall survival at 5 years was 34%. The corresponding cumulative incidence of non-relapse mortality and relapse was 26% and 41%, respectively. In multivariable analysis, factors significantly associated with overall survival were the use of TBI (HR, 0.57; P = .021), age >35 years (HR, 1.55; P = .025), and disease status at HCT (HR, 1.98; P = .005 for relapsed/refractory disease compared with CR). Relapse was the most common cause of death (58% of patients). Allogeneic HCT remains a potentially curative option in selected patients with adult T-ALL, although relapse is a major cause of treatment failure., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The maximum age of patients receiving allogeneic hematopoietic stem cell transplantation (alloHCT) has been moving up over time. However, the availability of a suitable HLA-matched sibling donor may limit access of this patient population to alloHCT. We retrospectively investigated the outcomes of umbilical cord blood transplantation (UCBT) after reduced-intensity conditioning regimens in patients aged ≥70 years with myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) between 2010 and 2014. During this period 70 patients with AML/MDS were referred to our center for alloHCT consideration. Twenty-two patients (33%) received alloHCT: 10 UCBT, 9 HLA full-matched sibling donor transplantation, 2 haploidentical alloHCT, and 1 unrelated donor alloHCT. In UCBT, cumulative incidences of nonrelapse mortality and relapse were 20% and 30% at 2 years, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) at day +100 and chronic GVHD at 2 years was 10%. Seven patients had viral reactivation/infections. Rates of overall survival and disease-free survival were 60% and 50% at 2 years, respectively. Moreover, these outcomes seemed to be similar to that of patients aged 60 to 69 years receiving UCBT (n = 60) and patients aged ≥70 years receiving HLA full-matched sibling donor transplantation (n = 9). These results suggest that UCBT is feasible in selected AML/MDS patients aged ≥70 years. In fact, UCBT shortens the required time for an unrelated donor search and thus increases the chance of proceeding with alloHCT, which might contribute to higher rates of alloHCT in the referral group. Outcomes of UCBT are promising; however, larger studies with a longer follow-up are needed., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Data on pretransplantation minimal residual disease (MRD) and outcomes of umbilical cord blood transplantation (UCBT) are limited. Out of the 143 patients with acute lymphoblastic leukemia (ALL) who underwent UCBT at the University of Minnesota between 2004 and 2010, we evaluated 86 patients with available MRD assessment data by 4- and 8-color flow cytometry analysis immediately before transplantation. Ten patients (11.6%) were MRD-positive, and 76 were MRD-negative (88.4%). Most of the patients (82%) received myeloablative conditioning. GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. In multivariate analysis, age, disease status (complete remission [CR] 1 versus CR2/CR3), disease group (precursor B cell ALL versus Philadelphia chromosome-positive ALL versus T cell ALL), and time to transplantation had no impact on relapse. Patients with MRD before UCBT had a greater incidence of relapse at 2 years (relapse rate, 30%; 95% confidence interval [CI], 4%-56%) and lower 3-year disease-free survival (30%; 95% CI, 7%-58%) compared with those without MRD (relapse rate, 16%; 95% CI, 8%-25%; P = .05; disease-free survival, 55%; 95% CI, 43%-66%; P = .02). Our data suggest that in patients with ALL, achieving an MRD-negative state before UCBT improves outcomes., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)