In this study, we analyzed the long-term outcome of a risk-adapted transplantation strategy for mantle cell lymphoma in 121 patients enrolled in sequential transplantation protocols. Notable developments over the 17-year study period were the addition of rituximab to chemotherapy and preparative regimens and the advent of nonmyeloablative allogeneic stem cell transplantation (NST). In the autologous transplantation group (n ‫؍‬ 86), rituximab resulted in a marked improvement in progression-free survival for patients who received a transplant in their first remission (where a plateau emerged at 3-8 years) but did not change the outcomes for patients who received a transplant beyond their first remission. In the NST group, composed entirely of patients who received a transplant beyond their first remission, durable remissions also emerged in progression-free survival at 5 to 9 years. The major determinants of disease control after NST were the use of a peripheral blood stem cell graft and donor chimerism of at least 95%, whereas the major determinant of death was immunosuppression for chronic graft-versushost disease. Our results show that longterm disease-free survival in mantle cell lymphoma is possible after rituximabcontaining autologous transplantation for patients in first remission and after NST for patients with relapsed or refractory disease.

For patients with acute lymphoblastic leukemia (ALL) who relapse after allogeneic hematopoietic stem cell transplantation (HSCT), treatment options are limited, and the clinical course and prognostic factors affecting outcome have not been well characterized. We retrospectively analyzed outcomes of 123 adult patients with ALL who relapsed after a first HSCT performed at our center between 1993 and 2011. First-line salvage included second HSCT (n = 19), donor lymphocyte infusion with or without prior chemotherapy (n = 11), radiation therapy (n = 6), cytoreductive chemotherapy (n = 30), mild chemotherapy (n = 27), or palliative care (n = 23), with median postrelapse overall survival (OS) of 10 months, 6.5 months, 3 months, 4 months, 4 months, and 1 month, respectively. Despite a complete remission rate of 38% after first-line salvage in the treated patients, the OS rate remained limited with 1- and 2- year OS rates of 17% (95% confidence interval, 13 to 29) and 10% (95% confidence interval, 6 to 20), respectively. On univariate analysis, adverse factors for OS included active disease at the time of first HSCT and short time to progression from first HSCT (<6 months). There was no difference in the 6-month survival postrelapse in patients with isolated extramedullary relapse (44%) compared with combined extramedullary and bone marrow relapse (29%) or those with isolated bone marrow relapse (34%) (P = .8). Our data provide more insight into the disease behavior and treatment outcomes of ALL at relapse after HSCT against which future trials may be compared.

This study aims to provide a detailed analysis of allogeneic stem cell transplantation (allo-SCT) outcomes in a large T-cell acute lymphoblastic leukemia (T-ALL) cohort with a specific emphasis on the effects of pre-transplant minimal residual disease (MRD) and disease subtype, including the aggressive early-thymic precursor (ETP) subtype. Data from 102 allo-SCT patients with a diagnosis of T-ALL from three centers were retrospectively analyzed. Patients were grouped into four T-ALL subtypes: ETP, early, cortical and mature. At 3 years, overall survival (OS), PFS, non-relapse mortality and cumulative incidence (CI) progression were 35, 33, 11 and 55%, respectively. Patients transplanted in first complete remission (CR1) had a 3-year OS of 62% versus those transplanted in CR2 or greater (24%) (hazards ratio 1.6, P=0.2). Patients with MRD positivity at the time of transplant had significantly higher rates of progression compared with those with MRD negativity (76 vs 34%, hazards ratio 2.8, P=0.006). There was no difference in OS, PFS or cumulative incidence (CI) progression between disease subtypes, including ETP (n=16). ETP patients transplanted in CR1 (n=10) had OS of 47%, comparable to other disease subtypes, suggesting that allo-SCT can overcome the poor prognosis associated with ETP. MRD status at transplant was highly predictive of disease relapse, suggesting novel therapies are necessary to improve transplant outcomes.

Fluid overload (FO) is commonly seen during hospitalization for allogeneic hematopoietic stem-cell transplantation (AHSCT). We hypothesized that FO is associated with transplant outcomes and evaluated this complication in two cohorts of patients and graded based on post-transplant weight gain, symptoms, and need for treatment, and was scored in real time by an independent team. The first cohort (study cohort) underwent haploidentical transplantation for hematologic malignancies (N=145) following a melphalan-based conditioning regimen. In univariate analysis, factors associated with Day 100 non-relapse mortality (NRM) were FO Grade ≥2 (HR=15, CI 4.2–55, p<0.001), creatinine >1 mg/dL (HR=4.7, CI 1.6–14, p=0.005), and age >55 years (HR=4.5, CI 1.5–13, p=0.008). In multivariate analysis, factors associated with Day 100 NRM were FO Grade ≥2 (HR=13.1, CI 3.4–50, p<0.001) and creatinine >1 mg/dL at transplant admission (HR=3.5, CI 1.1–11, p=0.03). These findings were verified in a separate cohort (validation cohort) of patients with acute myeloid leukemia/myelodysplastic syndrome who underwent HLA-matched transplant (N=449) with busulfan-based conditioning. In multivariate analysis, factors associated with Day 100 NRM were FO Grade ≥2 (HR=34, CI 7.2–158, p<0.001) and, in patients with FO Grade <2, advanced disease status (HR=5, CI 1.1–22, p=0.03). A higher NRM translated to significantly poorer 1-year overall survival rates for patients with FO ≥2 than for patients without FO, 70% vs. 42% (p<0.001) in the study cohort and 64% vs. 38% (p<0.001) in the validation cohort. In conclusion, FO Grade ≥2 is strongly associated with higher NRM and shorter survival and should be considered an important prognostic factor in transplantation.

We investigated the administration of intravenous (i.v.) busulfan (Bu) combined with melphalan (Mel) in patients with advanced lymphoid malignancies undergoing autologous SCT. Bu 130 mg/m2 was infused daily for 4 days, either as a fixed dose per BSA, or to target an average daily AUC of 5,000 uMol-min, determined by a test dose of i.v. Bu at 32 mg/m2 given 48 hours prior to the high dose regimen, followed by a rest day, followed by two daily doses of Mel at 70mg/m2. Stem cells were infused the following day. 80 patients had i.v. Bu delivered per test dose guidance. The median daily systemic Bu exposure was 4867 uMol-min. 102 patients [Hodgkin's Lymphoma (HL) n=49, Non Hodgkin's Lymphoma (NHL) n=12, Multiple Myeloma (MM) =41] with median age 44 years (range 19 to 65 years) were treated. 2-year overall survival (OS) and progression-free survival (PFS) rates were 85% and 57%, respectively, for patients with HL, 67% and 64%, respectively, for patients with NHL, and 82% and 42%, respectively, for patients with MM. The regimen was very well-tolerated with treatment-related mortality at 100 days, 1 year, and 2 years of 1%, 3%, and 3%, respectively. Intravenous Bu-Mel is well-tolerated. Disease control is encouraging, and should be explored in larger phase II studies.