[Show abstract][Hide abstract] ABSTRACT: We describe 47 patients with lymphoma and failed prior autologous hematopoietic cell transplantation (HCT) who received TLI-ATG (anti-thymocyte globulin) conditioning followed by allogeneic HCT. Thirty-two patients had non-Hodgkin lymphoma (NHL; diffuse large B-cell lymphoma (n=19), T-cell NHL (n=6), mantle cell lymphoma (n=4) or other B-cell subtypes (n=3)), and 15 had Hodgkin lymphoma. The median follow-up was 4.9 (range, 2.1-11.9) years. The cumulative incidence of grade II-IV acute GvHD at day +100 was 12%, and the cumulative incidence of extensive chronic GvHD at 1 year was 36%. The 3-year cumulative incidences of overall survival (OS), PFS and non-relapse mortality (NRM) were 81%, 44% and 7%, respectively. Fifteen patients died (relapse, n=10; NRM, n=5). Among the 25 patients with relapse after allogeneic HCT, 11 (44%) achieved durable (>1 year) CRs following donor lymphocyte infusion or chemoradiotherapy. The majority of surviving patients (75%; n=24) were able to discontinue all immunosuppression. For patients with relapsed lymphoma after autologous HCT, allogeneic HCT using TLI-ATG conditioning is a well-tolerated, predominantly outpatient therapy with low NRM (7% at 3 years), a low incidence of GvHD, durable disease control and excellent OS (81% at 3 years).Bone Marrow Transplantation advance online publication, 6 July 2015; doi:10.1038/bmt.2015.149.
Bone marrow transplantation 07/2015; DOI:10.1038/bmt.2015.149 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Alternative donor transplantation is increasingly used for high-risk lymphoma patients. We analyzed 1593 transplant recipients (2000-2010) and compared transplant outcomes in recipients of 8/8 allele HLA-A, -B, -C and DRB1 matched unrelated donors (MUDs; n=1176), 7/8 allele HLA mismatched unrelated donors (MMUDs; n=275) and umbilical cord blood donors (1 or 2 units UCB; n=142). Adjusted 3-year non-relapse mortality of MMUD (44%) was higher as compared with MUD (35%; P=0.004), but similar to UCB recipients (37%; P=0.19), although UCB had lower rates of neutrophil and platelet recovery compared with unrelated donor groups. With a median follow-up of 55 months, 3-year adjusted cumulative incidence of relapse was lower after MMUD compared with MUD (25% vs 33%, P=0.003) but similar between UCB and MUD (30% vs 33%; P=0.48). In multivariate analysis, UCB recipients had lower risks of acute and chronic GVHD compared with adult donor groups (UCB vs MUD: hazard ratio (HR)=0.68, P=0.05; HR=0.35; P<0.001). Adjusted 3-year OS was comparable (43% MUD, 37% MMUD and 41% UCB). These data highlight the observation that patients with lymphoma have acceptable survival after alternative donor transplantation. MMUD and UCB can extend the curative potential of allotransplant to patients who lack suitable HLA matched sibling or MUD.Bone Marrow Transplantation advance online publication, 17 November 2014; doi:10.1038/bmt.2014.259.
Bone Marrow Transplantation 11/2014; 50(2). DOI:10.1038/bmt.2014.259 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients and physicians may defer unrelated donor hematopoietic cell transplantation (HCT) as curative therapy due to mortality risk associated with the procedure. Therefore, it is important for physicians to know the current outcomes data when counseling potential candidates. To provide this information, we evaluated 15,059 unrelated donor HCT recipients between 2000-2009. We compared outcomes before and after 2005 for four cohorts: age <18 years with malignant diseases (N=1,920), 18-59 years with malignant diseases (N=9,575), ≥60 years with malignant diseases (N=2,194), and non-malignant diseases (N=1,370). Three-year overall survival in 2005-2009 was significantly better in all four cohorts (<18 years: 55% vs. 45%, 18-59 years: 42% vs. 35%, ≥60 years: 35% vs. 25%, non-malignant diseases: 69% vs. 60%, P<0.001 for all comparisons). Multivariate analyses in leukemia patients receiving HLA 7-8/8 matched transplants showed significant reduction in overall and non-relapse mortality in the first 1-year after HCT among patients transplanted in 2005-2009; however, risks for relapse did not change over time. Significant survival improvements after unrelated donor HCT have occurred over the recent decade and can be partly explained by better patient selection (e.g., HCT earlier in the disease course and lower disease risk), improved donor selection (e.g., more precise allele-level matched unrelated donors) and changes in transplant practices.
Biology of Blood and Marrow Transplantation 10/2014; 21(1). DOI:10.1016/j.bbmt.2014.10.001 · 3.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract DLBCL is the most common non-Hodgkin lymphoma histology with 40% of patients cured with frontline therapy. Salvage chemotherapy followed by autologous HCT remains the standard of care for relapsed or primary refractory patients who are chemosensitive. Autologous HCT in first remission is not recommended as randomized trials have not shown a survival benefit. Despite evidence for a graft vs lymphoma effect, allogeneic HCT is often reserved for DLBCL patients who have persistent marrow involvement, who have failed autologous HCT or have primary refractory disease. Reduced intensity or non-myeloablative conditioning regimens carry a lower non-relapse mortality risk as compared to myeloablative conditioning but are associated with higher relapse. DLBCL patients with the dual translocations of bcl2 and myc or 'double hit' lymphoma carry a poor prognosis and HCT is often offered as consolidation therapy. Further studies are needed to determine if HCT can alter the natural history of this aggressive subtype.
Leukemia and Lymphoma 10/2014; 56(7):1-22. DOI:10.3109/10428194.2014.975803 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Blood and Marrow Transplant Clinical Trials Network conducts large, multi-institutional clinical trials with the goal of improving the outcomes of hematopoietic cell transplantation (HCT) for patients with life-threatening disorders. Well designed HCT trials benefit from standardized criteria for defining diagnoses, treatment plans and graft source selection. In this perspective, we summarize evidence supporting criteria for the selection of related and unrelated adult volunteer progenitor cell donors or umbilical cord blood units. These standardized criteria for graft source selection have been adopted by the BMT CTN to enhance the interpretation of clinical findings within and among future clinical protocols.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 09/2014; 21(1). DOI:10.1016/j.bbmt.2014.09.017 · 3.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe outcomes after allogeneic hematopoietic cell transplantation (HCT) for mycosis fungoides and Sezary syndrome (MF/SS). Outcomes of 129 subjects with MF/SS reported to the Center for the International Blood and Marrow Transplant from 2000-2009. Median time from diagnosis to transplant was 30 (4-206) months and most subjects were with multiply relapsed/ refractory disease. The majority (64%) received non-myeloablative conditioning (NST) or reduced intensity conditioning (RIC). NST/RIC recipients were older in age compared with myeloablative recipients (median age 51 vs 44 years, P=0.005) and transplanted in recent years. Non-relapse mortality (NRM) at 1 and 5 years was 19% (95% confidence interval (CI) 12-27%) and 22% (95% CI 15-31%), respectively. Risk of disease progression was 50% (95% CI 41-60%) at 1 year and 61% (95% CI 50-71%) at 5 years. PFS at 1 and 5 years was 31% (95% CI 22-40%) and 17% (95% CI 9-26%), respectively. OS at 1 and 5 years was 54% (95% CI 45-63%) and 32% (95% CI 22-44%), respectively. Allogeneic HCT in MF/SS results in 5-year survival in approximately one-third of patients and of those, half remain disease-free.Bone Marrow Transplantation advance online publication, 28 July 2014; doi:10.1038/bmt.2014.161.
Bone Marrow Transplantation 07/2014; 49(11). DOI:10.1038/bmt.2014.161 · 3.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Blood Cancer Journal is a peer-reviewed, open access online journal publishing pre-clinical and clinical work in the field of hematology with ramifications into translational biology research down to new therapies
Blood Cancer Journal 05/2014; 4(5):e216. DOI:10.1038/bcj.2014.35 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Allogeneic hematopoietic cell transplantation (allo HCT) is the only curative therapy for the Myelodysplastic Syndromes (MDS) and Myeloproliferative Neoplasms (MPN), but treatment related toxicity has been a barrier to its more widespread use. The non-myeloablative regimen of Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin (ATG) permits the establishment of donor hematopoiesis necessary for the graft versus malignancy (GVM) effect and is protective against acute Graft versus Host Disease (aGVHD) but has minimal direct cytotoxicity against myeloid diseases. We explored the use of TLI-ATG conditioning to treat 61 patients with allo HCT for MDS (n= 32), therapy-related myeloid neoplasms (n=15), MPN (n=9) and CMML (n=5). The median age of all patients was 63 years (range 50-73). The cumulative incidence of aGVHD Grades II-IV was 14% (95% CI 4-23%) and Grades III-IV 4% (0-9%) and did not differ between patients that received allografts from related or unrelated donors. The cumulative incidence of non-relapse mortality (NRM) at 100 days, 12 months, and 36 months was 0%, 7%, and 11%. Overall survival (OS) and progression-free survival (PFS) were 41% (29-53%) and 35% (23-48%) respectively. The safety and tolerability of TLI-ATG, as exemplified by its low non-relapse mortality, provides a foundation for further risk-adapted or prophylactic interventions to prevent disease progression.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2014; 20(6). DOI:10.1016/j.bbmt.2014.02.023 · 3.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the outcomes of patients with chemotherapy-sensitive mantle-cell lymphoma (MCL) following a first hematopoietic stem-cell transplantation (HCT), comparing outcomes with autologous (auto) versus reduced-intensity conditioning allogeneic (RIC allo) HCT and with transplantation applied at different times in the disease course.
In all, 519 patients who received transplantations between 1996 and 2007 and were reported to the Center for International Blood and Marrow Transplant Research were analyzed. The early transplantation cohort was defined as those patients in first partial or complete remission with no more than two lines of chemotherapy. The late transplantation cohort was defined as all the remaining patients.
Auto-HCT and RIC allo-HCT resulted in similar overall survival from transplantation for both the early (at 5 years: 61% auto-HCT v 62% RIC allo-HCT; P = .951) and late cohorts (at 5 years: 44% auto-HCT v 31% RIC allo-HCT; P = .202). In both early and late transplantation cohorts, progression/relapse was lower and nonrelapse mortality was higher in the allo-HCT group. Overall survival and progression-free survival were highest in patients who underwent auto-HCT in first complete response. Multivariate analysis of survival from diagnosis identified a survival benefit favoring early HCT for both auto-HCT and RIC allo-HCT.
For patients with chemotherapy-sensitive MCL, the optimal timing for HCT is early in the disease course. Outcomes are particularly favorable for patients undergoing auto-HCT in first complete remission. For those unable to achieve complete remission after two lines of chemotherapy or those with relapsed disease, either auto-HCT or RIC allo-HCT may be effective, although the chance for long-term remission and survival is lower.
[Show abstract][Hide abstract] ABSTRACT: Hodgkin Lymphoma (HL) prognostic models based on factors measured at time of autologous hematopoietic cell transplantation (AHCT) are limited by small sample sizes. Models based on information at diagnosis are often not uniformly collected or available at transplantation. We propose an easily implementable prognostic model for progression-free survival (PFS) post-AHCT based on factors available at transplantation in a large international cohort of HL patients. The outcomes of 728 AHCT recipients for relapsed/refractory HL were studied. Patients were randomly selected for model development (n=337) and validation (n=391). The multivariate model identified four major adverse risk factors at the time of AHCT with the following relative weights: Karnofsky performance score <90 and chemotherapy resistance at AHCT were each assigned 1 point while >3 chemotherapy regimens pre-AHCT and extra-nodal disease at AHCT were each assigned 2 points. Based on the total score summed for the four adverse risk factors, three risk groups were identified: Low, (score=0), Intermediate, (score=1-3) or High, (score=4-6). The 4-year PFS (95% CI) for the Low (N=176), Intermediate (N=261) and High (N=283) risk groups were 71% (63-78%), 60% (53-66%), and 42% (36-49%), respectively. The prognostic model was validated in an independent cohort. The CIBMTR Model is based on factors easily available at the time of AHCT and discriminates patients with favorable post-AHCT outcomes as well as an intermediate risk group. This model should assist in the prospective evaluation of alternative treatment strategies.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 10/2013; 19(12). DOI:10.1016/j.bbmt.2013.09.018 · 3.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We conducted a prospective cohort study testing the non-inferiority of survival of ablative IV-BU versus ablative TBI-based regimens in myeloid malignancies. 1,483 patients transplanted for myeloid malignancies (IV-BU, N=1025, TBI, N=458) were enrolled. Cohorts were similar with respect to age, gender, race, performance score, disease and disease stage at transplant. Most patients had acute myeloid leukemia (68% IV-BU, 78% TBI). Grafts were primarily peripheral blood (77%) from HLA-matched siblings (40%) or well-matched unrelated donors (48%). Two-year probabilities of survival (95% CI), were 56% (53-60%) and 48% (43-54%, p=0.019) for IV-BU (Relative Risk 0.82, 0.68-0.98, p=0.03) and TBI, respectively. Corresponding incidences of transplant related mortality (TRM) were 18% (16-21%) and 19% (15-23%, p= 0.75) and disease progression were 34% (31-37%) and 39% (34-44%, p=0.08). The incidence of hepatic veno-occlusive disease (VOD) was 5% for IV-BU and 1% with TBI (p < 0.001). There were no differences in progression-free survival and graft-versus-host disease. Compared to TBI, IV-BU resulted in superior survival with no increased risk of relapse or TRM. These results support the use of myeloablative IV-BU over TBI-based conditioning regimens for treatment of myeloid malignancies.