HLA-haploidentical Peripheral Blood Stem Cell Research Articles

RAISING revealed a heterogenous pattern of HTLV-1 clonality after HLA-haploidentical peripheral blood stem cell transplantation for ATL.

RAISING revealed a heterogenous pattern of HTLV-1 clonality after HLA-haploidentical peripheral blood stem cell transplantation for ATL.

HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide versus HLA-Matched Unrelated Donor Transplantation for Myelodysplastic Syndrome

HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide versus HLA-Matched Unrelated Donor Transplantation for Myelodysplastic Syndrome

Comparable survival outcomes with haploidentical stem cell transplantation and unrelated bone marrow transplantation.

We retrospectively compared outcomes of unrelated donor bone marrow transplant (UBMT) and HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide (PTCy-haploPBSCT) using the Japanese registry data. Recipients of first HCT for acute leukemia and myelodysplastic syndromes between 2012 and 2015 were included. The analyzed subjects comprised UBMT recipients with 8/8 matched HLA alleles (n = 1470), 7/8 matched alleles (n = 859), 6/8 matched alleles (n = 186), and recipients of PTCy-haploPBSCT (n = 133). In multivariate analyses with 8/8 matched UBMT as the reference, PTCy-haploPBSCT showed similar overall mortality, decreased risk of non-relapse mortality (NRM), increased risk of relapse, and decreased risk of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD. Adjusted probabilities for 8/8 matched UBMT, PTCy-haploPBSCT, and 7/8 and 6/8 matched UBMT groups at 2 years post-transplant were 61%, 60%, 58%, and 52% for overall survival, 23%, 28%, 21%, and 19% for relapse, and 20%, 7%, 24%, and 33% for NRM. PTCy-haploPBSCT was associated with remarkably low NRM, contributing to survival outcomes that were comparable to 8/8 matched UBMT. The higher relapse rate in the PTCy-haploPBSCT group might be associated with the higher proportion of high-risk patients. PTCy-haploPBSCT may be a viable alternative when HLA-matched related donors are not available.

Immune reconstitution and survival of patients with parvovirus B19 related pure red cell aplasia after haplo-PBSCT.

Parvovirus B19 (PvB19) infection and PvB19 related pure red cell aplasia (PRCA) in recipients with allogeneic hematopoietic stem cell transplantation have been reported sporadically. However, clinical studies with large sample sizes are lacking, especially in patients undergoing HLA-haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). In addition, clinical features, immune reconstitution, and outcomes of these patients are not clear. We conducted a retrospective analysis of 164 patients who received haplo-PBSCT with low-dose anti-thymocyte globulin (ATG) plus low-dose posttransplant cyclophosphamide (PTCy)-based regimen as graft-versus-host disease (GVHD) prophylaxis. We analyzed the incidence of PvB19 related PRCA and compared the clinical characteristics, immune reconstitution, incidence of GVHD, relapse rate, and survival between patients with and without PvB19 related PRCA. A total of 14 (8.5%) recipients developed PvB19 related PRCA after a median of 5.3 months after haplo-PBSCT. These patients with PvB19 related PRCA had slower immune reconstitution, but similar incidences of GVHD, relapse rate, and overall survival compared with recipients without PvB19 related PRCA. PvB19 related PRCA indicated relative delayed and poor immune reconstitution of the recipients early after haplo-PBSCT. PvB19 related PRCA had no effects on GVHD, relapse, and survival.

HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning with very low-dose antithymocyte globulin for relapsed/refractory acute leukemia in pediatric patients: a single-institution retrospective analysis.

The prognosis of relapsed/refractory (R/R) pediatric acute leukemia is extremely poor. We retrospectively reviewed 20 consecutive pediatric patients with R/R acute leukemia who underwent a first HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning (haplo-RIC-PBSCT) with very low-dose antithymocyte globulin (ATG) between 2012 and 2019. Of these 20 patients, 7 patients had acute lymphoblastic leukemia, and 13 had acute myeloid leukemia. At the time of haplo-RIC-PBSCT, 15 patients had active disease. The median follow-up duration for survivors was 56months (range 22-108months). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, short-term methotrexate, methylprednisolone, and ATG 1.25mg/kg on day-2. The 2-year cumulative incidence of transplant-related mortality and relapse were 5.0% [95% confidence interval (CI) 0.7-30.5%)] and 57.8% (95% CI 37.4-79.6%), respectively. Among the 20 patients, 16 (80.0%) developed grade III-IV acute GVHD, and 2 developed severe chronic GVHD. The 2-year event-free survival and overall survival rates were 40.0% (95% CI 19.3-60.0%) and 50.0% (95% CI 27.1-69.2%), respectively. Although the sample size is small, the survival outcomes of the present study are encouraging.

A Prospective Study of an HLA-Haploidentical Peripheral Blood Stem Cell Transplantation Regimen Based on Modification of the Dose of Posttransplant Cyclophosphamide for Poor Prognosis or Refractory Hematological Malignancies

The optimal dose of posttransplant cyclophosphamide (PTCy) for use in patients undergoing HLA-haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide (PTCy-haplo) has not been sufficiently examined. This study evaluates the safety and efficacy of HLA-haploidentical hematopoietic cell transplantation with a reduced dose of PTCy for patients with a poor prognosis or those with refractory hematological malignancies. We conducted a prospective clinical study of PTCy-haplo with peripheral blood stem cells (PBSCs) using a modified PTCy dosage regimen consisting of 50 mg/kg on day 3 posttransplantation and a reduced dose of 25 mg/kg on day 4. The cumulative incidences of grades II to III and IV acute graft-versus-host disease (GVHD) at day 100 posttransplantation were 30% and 0%, respectively. The cumulative incidence of moderate-to-severe chronic GVHD after transplantation was 7.0%. The cumulative incidence of nonrelapse mortality at 1 year posttransplantation was 6.1%. Overall survival (OS) at 1 year was 66%. In addition, the restricted cubic-spline Cox regression analysis showed nonlinear relationship between the number of infused CD34+ cells and CD3+ cells, and OS. A graft composition of >4.54 × 106/kg CD34+ cells and >1.85 × 108/kg but ≤3.70 × 108/kg CD3+ cells was significantly associated with better survival, irrespective of the disease status (hazard ratio, 0.13; 95% confidence interval, 0.04–0.41; P < 0.001). These results suggest that PTCy-haplo with PBSCs using a de-escalated dose of 50 mg/kg on day 3 and 25 mg/kg on day 4 posttransplantation is a feasible option.

HLA-haploidentical peripheral blood stem cell transplantation with post-transplantation cyclophosphamide for adult T-cell leukemia

Recently, allogeneic peripheral blood stem cell transplantation from human leukocyte antigen (HLA)-haploidentical donors using post-transplantation cyclophosphamide (PTCY-haploPBSCT) has become available in clinical practice. However, the efficacy of PTCY in adult T-cell leukemia (ATL) is not fully established yet. In this study, we retrospectively examined data of seven patients who underwent PTCY-haploPBSCT. The overall survival rate at 100 days after transplantation was 85.7%, and the 1-year overall survival rate was 68.6%. The cumulative incidence of relapse at 1 year was 31.4%, whereas the 1-year nonrelapse mortality was 17.1%. The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) on day 100 was 14.3%, and the incidence of chronic GVHD at 1 year was 33.3%. These results suggest that PTCY-haploPBSCT can be a viable option even in patients with ATL. Further accumulation of knowledge and improvement of transplantation outcomes are warranted in the future.

Lower Absolute Lymphocyte Count Before Conditioning Predicts High Relapse Risk in Patients After Haploidentical Peripheral Blood Stem Cell Transplantation With Low Dose Anti-Thymocyte Globulin/Post-Transplant Cyclophosphamide for GvHD Prophylaxis

Standard anti-thymocyte globulin (ATG) weight-based dosing often resulted in highly variable ATG exposure, which had profound effects on relapse and survival, especially in recipients with relatively low absolute lymphocyte count (ALC) before conditioning. Data regarding rabbit ATG pharmacokinetics and pharmacodynamics in the setting of HLA-haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) is lacking. We conducted a retrospective study on 90 consecutive patients who underwent haplo-PBSCT with low dose rabbit ATG (5 mg/kg) plus low dose post-transplant cyclophosphamide (50 mg/kg) based regimen for graft-versus-host disease (GvHD) prophylaxis. We compared serum concentration of ATG and post-transplant results between patients with ALC<500/μl and ALC≥500/μl before conditioning. Patients with ALC<500/μl had higher ATG concentrations, delayed immune reconstitution, lower incidence of grade II-IV acute GvHD (0 vs. 19.42%, P = 0.043), higher risk of Epstein-Barr virus infection within 100 days post-transplant (47.78% vs. 22.22%, P = 0.020) and 1-year relapse rate (33.33% vs.11.59%, P = 0.041), and lower 1-year overall survival (OS) (52.38% vs.79.71%, P = 0.004), 1-year relapse free survival (RFS) (47.62% vs. 75.36% for RFS, P = 0.014), and 1-year GvHD free relapse-free survival (GRFS) (42.89% vs. 65.22%, P = 0.043). ALC<500/μl before conditioning was a significant poor risk factor for relapse, OS, RFS, and GRFS.

Letermovir Is Effective for Prevention of Cytomegalovirus Reactivation in HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide

[Introduction] Cytomegalovirus (CMV) infection is a common viral infection in recipients of allogeneic hematopoietic stem cell transplantation (allo-SCT). Early CMV reactivation after allo-SCT is associated with worse non-relapse mortality (NRM) and overall survival (OS). Recently, T-cell replete HLA-haploidentical SCT using post-transplant cyclophosphamide (PTCy-haplo SCT) has been developed and spread rapidly worldwide. Rationale of this strategy is assumed to be selective and cytotoxic depletion of alloreactive T cells which are responsible for graft-versus-host disease (GVHD), while preserving non-alloreactive T cells which can contribute to fight infections. However, recent studies showed that PTCy-haplo SCT was associated with the increased incidence of CMV infection. Letermovir (LET), a novel anti-CMV agent, which inhibits the CMV DNA terminase complex, was approved for the prevention of CMV reactivation in allo-SCT recipients in 2018 in some countries including Japan based on the result of a phase 3 trial. Our facility performs LET prophylaxis in allo-SCT recipient if either donor or recipient is seropositive CMV. Although LET is effective for the prevention of CMV reactivation in allo-SCT recipients, the clinical effectiveness of LET prophylaxis in PTCy-haplo SCT is not well elucidated. Based on these things, we retrospectively evaluated the efficacy of LET prophylaxis in PTCy-haplo SCT.[Methods] We retrospectively analyzed consecutive 99 recipients who received PTCy-haplo SCT at Hokkaido University Hospital from March 2013 to March 2021. We compared the cumulative incidence of CMV reactivation between the LET prophylaxis group (LET group, 33 patients) and LET non-prophylaxis group (non-LET group, 66 patients). LET was initiated on the day 0 at a dosage of 480mg daily. All patients were monitored for CMV reactivation by using the anti-CMV pp65 monoclonal antibody HRP-C7 assay at least once a week from the time of engraftment. CMV reactivation was defined as the detection of CMV antigen positive cells per 50000 white blood cells, whereas CMV disease was defined by organ dysfunction attributable to CMV.[Results] As baseline patient's characteristics were summarized in Table1, there were no difference between LET and non-LET group in terms of age, sex, underlying disease, disease risk at transplantation, prior transplantation, conditioning intensity, and CMV serostatus. All patients received peripheral blood stem cell transplantation. GVHD prophylaxis consisted of Cy (40-50 mg/kg on day 3 and 4), tacrolimus (from day 5), and mycophenolate mofetil (from day 5). The cumulative incidence of CMV reactivation at 150 days after transplantation in LET group was significantly lower than that in non-LET group (30.3% versus 69.7%; P <.001, Figure1A). Importantly, CMV disease were occurred in three patients without LET prophylaxis (gastritis, enteritis, and retinitis), but not in the patients with LET prophylaxis. The cumulative incidence of NRM at 1 year was similar between the patients with and without LET prophylaxis (17.6% versus 9.2%; P=0.366, Figure1B), as was OS at 1 year (71.5% versus 69.4%; P=0.801, Figure1C). Neutrophil engraftment was achieved in 32 patients (97%) at a median of 15 days in LET group and 64 patients (97%) at a median of 14.5 days in non-LET group (P=0.243). Furthermore, platelet engraftment was achieved in 26 patients (79%) at a median of 34 days in LET group and 57 patients (86%) at a median of 31 days in non-LET group (P=0.282). These findings suggest that LET does not affect engraftment. Interestingly, the length of hospitalization in the LET group was significantly shorter than that in non-LET group (the median, 59.5 days versus 71 days; P=0.0488), suggesting that LET suppresses CMV reactivation leading to early discharge.[Conclusion] To our best knowledge, this is the largest retrospective study about the efficacy of LET in PTCy-Haplo SCT. LET is effective for prevention of CMV reactivation in PTCy-haplo SCT. Further studies focused on the long term effect of LET prophylaxis in PTCy-haplo SCT, such as the incidence of relapse and chronic GVHD, is warranted. [Display omitted] DisclosuresNakagawa: AbbVie GK: Research Funding; Takeda Pharmaceutical Company: Research Funding. Teshima: Gentium/Jazz Pharmaceuticals: Consultancy; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc.: Honoraria; Nippon Shinyaku Co., Ltd.: Research Funding; CHUGAI PHARMACEUTICAL CO., LTD.: Research Funding; Fuji pharma CO.,Ltd: Research Funding; Takeda Pharmaceutical Company: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis International AG: Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; TEIJIN PHARMA Limited: Research Funding; Astellas Pharma Inc.: Research Funding; Bristol Myers Squibb: Honoraria; Janssen Pharmaceutical K.K.: Other; Kyowa Kirin Co.,Ltd.: Honoraria, Research Funding; Sanofi S.A.: Research Funding.

HLA-haploidentical stem cell transplantation using posttransplant cyclophosphamide.

HLA-haploidentical stem cell transplantation using posttransplant cyclophosphamide has spread rapidly worldwide. This strategy was initially developed in the setting of bone marrow transplantation following nonmyeloablative conditioning. Recently, peripheral blood stem cell grafts and/or myeloablative conditioning regimen have been widely used. In Japan, prospective, multicenter, phase II studies have been conducted by the Japan Study Group for Cell Therapy and Transplantation to evaluate the safety and efficacy of HLA-haploidentical peripheral blood stem cell transplantation using posttransplant cyclophosphamide (PTCy-haploPBSCT). In the first such study (JSCT Haplo 13 study), we demonstrated that PTCy-haploPBSCT after busulfan-based reduced-intensity conditioning (RIC) enables stable donor engraftment and low incidences of both acute and chronic graft-versus-host disease (GVHD). In the second (JSCT Haplo 14 study), we showed that both myeloablative conditioning (MAC) and RIC are valid options for PTCy-haploPBSCT. Emerging evidence, including our findings, suggests that donor type (HLA-haploidentical donor versus HLA-matched related or unrelated donor) may no longer be a significant predictor of transplant outcome.

HLA-Haploidentical Peripheral Blood Stem Cell Transplantation With Post-transplant Cyclophosphamide and Bortezomib

HLA-Haploidentical Peripheral Blood Stem Cell Transplantation With Post-transplant Cyclophosphamide and Bortezomib

The Impact of Reduced Dose of Posttransplant Cyclophosphamide in HLA-Haploidentical Peripheral Blood Stem Cell Transplantation

HLA-haploidentical stem cell transplantation using posttransplant cyclophosphamide (PTCy-haploPBSCT) ensures good graft-versus-host disease (GVHD) controls and low non-relapse mortality (NRM), however, it remains to be elucidated whether dose-reduction of cyclophosphamide (CY) could be feasible. We conducted a prospective, multicenter, phase II study to evaluate the efficacy and safety of reduced-dose of PTCy in reduced-intensity conditioning (RIC) based PTCy-haploPBSCT (Haplo16 RIC, UMI20656). Conditioning regimen was fludarabine (150 mg/m2), busulfan (6.4 mg/kg), and total body irradiation (4 Gy). GVHD prophylaxis consisted of CY, tacrolimus and mycophenolate mofetil (MMF). The dose of CY was 40 mg/kg on days 3 and 4 (total 80 mg/kg). Tacrolimus was started from day 5, and MMF was started at a dose of 45 mg/kg/day from day 5 and discontinued with rapid taper after day 35. The primary endpoint was the incidence of grade III-IV acute GVHD. Fiftyseven patients with a median age of 61 (range, 18 to 60) were enrolled in this study between 2016 and 2017. Diagnoses included AML (n=14), ALL (n=7), MDS (n=13), lymphoma (n=16), and others (n=7). Thirty-six patients (63%) were not in remission and 16 patients (28%) had a history of prior allogeneic stem cell transplantation (allo-SCT). According to the refined disease risk index, 28 patients (49%) were classified as high / very high risk. Neutrophil engraftment was achieved in 97% with a median of 15 days. The incidence of grades IIIV and III-IV acute GVHD at days 100 were 26% and 7% (95%CI, 2-16%), respectively. The incidence of grade III-IV acute GVHD was clearly below the predefined threshold as the primary endpoint. All grade and moderate to severe chronic GVHD at 1-year were 35% and 19%, respectively. In the median follow-up period of 393 days (365-826), overall survival (OS), disease-free survival (DFS), NRM, and relapse rate (RR) at 1-year were 70%, 51%, 14%, and 35%, respectively. In our previous Haplo14 RIC study using CY at a dose of 50 mg/kg on days 3 and 4 (Sugita et al, BMT 2018), the incidences of grade II-IV and III-IV acute GVHD were 14% and 5%, respectively. All grade and moderate to severe chronic GVHD at 1-year were 23% and 17%, respectively. OS, DFS, NRM, and RR at 1-year were 52%, 43%, 18%, and 39%, respectively. We performed a retrospective comparison of the incidences of acute and chronic GVHD between Haplo16 RIC and Haplo14 RIC study. Although there was a trend for higher grade II-IV acute GVHD in Haplo16 RIC study (26% vs 14%, P=0.07), there was no significant difference in grade III-IV acute GVHD (7% vs 5%, P=0.41), all grade chronic GVHD (35% vs 23%, P=0.19), and moderate to severe chronic GVHD (19% vs 17%, P=0.81). Our results suggest that the reduction of PTCy is feasible in RIC based PTCy-haploPBSCT, although prospective studies are required to confirm our results.

Gene Polymorphism of Tacrolimus-Metabolizing Enzymes Associated With Impaired Absorption of Tacrolimus Following Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report

ObjectiveTo elucidate the mechanisms by which orally administered tacrolimus was not absorbed in a patient following allogeneic hematopoietic stem cell transplantation. Clinical CourseA 17-year-old girl with acute myeloid leukemia underwent HLA-haploidentical peripheral blood stem cell transplantation following fludarabine, busulfan, and total-body irradiation. Graft-vs-host disease prophylaxis was post-transplant cyclophosphamide, followed by intravenous tacrolimus and mycophenolate mofetil. When tacrolimus was switched to oral administration, its blood level declined rapidly, resulting in development of acute graft-vs-host disease, which was ameliorated by switching back to intravenous administration. Methods/ResultsTo elucidate if impaired tacrolimus absorption could be related to genetic polymorphism of tacrolimus-metabolizing enzymes, we analyzed gene polymorphisms of cytochrome P450 3A4, cytochrome P450 3A5, and multidrug resistance 1 (MDR1). The patient had wild-type cytochrome P450 3A4 (*1/*1) and variant-type cytochrome P450 3A5 (*3/*3), while MDR1 genes (2677A/G, 3435C/C) were wild-type. ConclusionWild-type MDR1 gene product P-glycoprotein expressed in the intestine reduces drug absorption from the gastrointestinal tract and may have contributed to low blood levels of tacrolimus in this patient when tacrolimus was orally administered.

Low Incidence of Chronic GVHD after HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post Transplantation Cyclophosphamide in Older Patients

Low Incidence of Chronic GVHD after HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post Transplantation Cyclophosphamide in Older Patients

HLA-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide after Busulfan-Containing Reduced-Intensity Conditioning

Allogeneic hematopoietic stem cell transplantation (allo-SCT) using post-transplant cyclophosphamide (PTCy) is increasingly performed. We conducted a multicenter phase II study to evaluate the safety and efficacy of PTCy-based HLA-haploidentical peripheral blood stem cell transplantation (PTCy-haploPBSCT) after busulfan-containing reduced-intensity conditioning. Thirty-one patients were enrolled; 61% patients were not in remission and 42% patients had a history of prior allo-SCT. Neutrophil engraftment was achieved in 87% patients with a median of 19 days. The cumulative incidence of grades II to IV and III to IV acute graft-versus-host disease (GVHD) and chronic GVHD at 1 year were 23%, 3%, and 15%, respectively. No patients developed severe chronic GVHD. Day 100 nonrelapse mortality (NRM) rate was 19.4%. Overall survival, relapse, and disease-free survival rates were 45%, 45%, and 34%, respectively, at 1 year. Subgroup analysis showed that patients who had a history of prior allo-SCT had lower engraftment, higher NRM, and lower overall survival than those not receiving a prior allo-SCT. Our results suggest that PTCy-haploPBSCT after busulfan-containing reduced-intensity conditioning achieved low incidences of acute and chronic GVHD and NRM and stable donor engraftment and low NRM, particularly in patients without a history of prior allo-SCT.

Prospective Multicenter Phase II Study of HLA-Haploidentical Peripheral Blood Stem Cell Transplantation after Reduced-Intensity Conditioning with Post-Transplant Cyclophosphamide: First Analysis of the JSCT Haplo13 Study

s / Biol Blood Marrow Transplant 21 (2015) S266eS321 S313 Mount Sinai, New York, NY; Medicine/BMT, Mount Sinai Hospital, New York NY; Mount Sinai Medical Center, New York, NY; Division of Hematology/Oncology, Mount Sinai School of Medicine, New York, NY; Bone Marrow and Stem Cell Transplantation, Icahn School of Medicine at Mount Sinai, New York, NY Background: The use of monoclonal antibodies in combination with chemotherapy for the treatment of lymphoma may improve efficacy by utilizing distinct mechanisms of tumor kill while minimizing overlapping toxicity. Bendamustine, a bifunctional alkylating agent, has been usedwith Rituximab in indolent non-Hodgkin lymphomas, chronic lymphocytic leukemia, and more recently for the treatment relapsed and refractory diffuse large B-cell lymphomas (DLBCL). Brentuximab, a monoclonal antibody targeting CD30, is approved for refractory and relapsed anaplastic large cell lymphoma, Hodgkin lymphoma relapsed after autologous stem cell transplant and may have efficacy in the treatment of DLBCL which have been shown to express CD30 in 14-25% of cases. We report the Mount Sinai Hospital experience using bendamustine and brentuximab (BB) in the treatment of relapsed-refractory lymphomas and its utility as a bridge to transplant. Methods: Retrospective analysis of the tolerability and outcomes for patients receiving BB between 2013 and 2014 as part of quality assurance review. Results: Seven patients (1 female) were identified with a median age of 39 (range 34-70). Diagnoses included Hodgkin lymphoma (4), primary mediastinal B-cell lymphoma (1), DLCBL (1), and peripheral T-cell enteropathy associated type II lymphoma (1). Median time between initial diagnosis and BB was 19 months (range 12-175 months). Patients received a mean of 4.1 prior lines of therapy (range 2-9) including allogeneic transplantation (1) and autologous transplantation (4). All patients received 90 mg/m2 of bendamustine and 1.8 mg/kg of brentuximab approximately every 3 weeks for a mean of 2.71 cycles. Two patients developed sepsis and fungal pneumonia, respectively. Of 6 patients evaluable for response, 4 had partial response, 1 hadmixed response and 1 had PR after 2 cycles, then received a stem cell boost/DLI but ultimately died from progression of disease (POD). 2 other patients received allogeneic stem transplants and 3 patients are awaiting transplantation. Conclusion: BB in our heterogeneous and heavily pretreated population has been well tolerated, has provided disease control, and has enabled patients to be bridged to transplant, both allogeneic and autologous.