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Background: Understanding the mortality patterns of patients with lymphoma and myeloma, who have undergone autologous hematopoietic stem cell transplantation (ASCT) might identify improvement opportunities., Patients and Methods: The present retrospective study included patients with lymphoma and myeloma, aged ≥ 18 years, who had undergone ASCT from 1983 to 2010 at the University of Nebraska Medical Center. Of the 2284 patients, 972 had died within first 5 years after ASCT. The patients were divided into 3 cohorts according to the time of transplantation: 1983 to 1990 (cohort I), 1991 to 2000 (cohort II), and 2001 to 2010 (cohort III). Using Cox proportional hazards regression analysis, the risk of cause-specific mortality was compared across the 3 cohorts., Results: Of a total of 1215 deaths, 972 (80%) occurred within the first 5 years after ASCT. Disease relapse (73.4%), organ failure (7.8%), infection (4.7%), and secondary malignancy (4.2%) accounted for most of the deaths. The risk of death from infection (P < .0001), but not from relapse (P = .26), organ failure (P = .68), or secondary malignancy (P = .15), had declined in the more recent cohorts., Conclusion: The 5-year overall survival of patients undergoing ASCT has improved significantly owing to a decline in infectious mortality. Our results highlight that the mortality from relapse remains the most common cause of death, warranting investigation of different strategies to reduce the incidence of relapse and improve the therapy for relapse after ASCT., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The creation of new cancer immunotherapies represents 1 of the most exciting advances taking place this decade. Although clinical studies continue to indicate improvement in clinical outcomes, the speed of its diffusion into actual practice is not known. It is important to understand practice variation in the use of recommended immunotherapies as new and more effective immunotherapies are developed. Additionally, as the field continues to grow, immunotherapy will encounter new barriers that will hinder its rapid adoption into clinical practice. This review aims to present a brief summary of the mechanisms and uses of antibody-based immunotherapies used to treat lymphoma and to present available practice variation data, including factors associated with variation. Review of the available data implicated patient characteristics and health care systems as being associated with practice variation; however, in several instances, ease of use, cost, toxicity, and physician knowledge contributed to variation, regardless of efficacy. As new immunotherapies are developed, these factors must be considered to increase the rapid diffusion of effective immunotherapies into wide clinical use., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The objective of this study was to examine the association between body mass index (BMI) and the incidence of pulmonary complications (PCs) after hematopoietic stem cell transplant (HCT). We reviewed 398 adult patients with non-Hodgkin lymphoma (NHL) who received autologous or allogeneic HCT between 1993 and 1997. BMI was classified as normal (18.5 < BMI ≤ 24.9), overweight (24.9 < BMI ≤ 30) and obese (BMI > 30). Multivariate logistic regression was used to analyze the relationship between BMI and presence of PCs within 100 days post-HCT while adjusting for patient-, disease- and transplant-related variables. The incidence of PCs within 100 days post-HCT was 32% (n = 129). Median BMI was 25.4 (range: 18.6-52.2). Median age was 48.8 years (range: 19.5-73.6 years). Multivariate analysis failed to show significant association between BMI and PCs. However, a total body irradiation (TBI)-based conditioning regimen was associated with lower rate of PCs.

A phase I/II trial was designed to evaluate the safety and efficacy of adding bortezomib to standard BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (ASCT). Eligible patients had relapsed/refractory indolent or transformed non-Hodgkin lymphoma or mantle cell lymphoma (MCL) that was relapsed/refractory or in first partial (PR) or complete remission (CR). Patients received bortezomib on days -11, -8, -5, and -2 before ASCT. Phase I had 4 dose cohorts (.8, 1, 1.3, and 1.5 mg/m(2)) and 3 patients were accrued to each. Any nonhematological ASCT-related toxicity >2 on the Bearman scale occurring between day -11 and engraftment defined the maximum tolerated dose (MTD). After the MTD has been reached, another 20 patients were enrolled at this dose to determine a preliminary overall response rate (ORR). Patients who were in CR or PR at day +100 were considered responders. The study enrolled 42 patients through August 14, 2009. The median age was 58 (range, 34 to 73) years, with 33 males and 9 females. The most common diagnoses were MCL (23 patients) and follicular lymphoma (7 patients). The median number of prior therapies was 1 (range, 0 to 6). The median follow-up was 4.88 (range, 1.07 to 6.98) years. Thirteen patients were treated in phase I and 29 patients were treated in phase II. The MTD was initially determined to be 1.5 mg/m(2) but it was later decreased to 1 mg/m(2) because of excessive gastrointestinal toxicity and peripheral neuropathy. The ORR was 95% at 100 days and 87% at 1 year. For all 38 evaluable patients at 1 year, responses were CR 84%, PR 1%, and progressive disease 13%. Progression-free survival (PFS) was 83% (95% CI, 68% to 92%) at 1 year, and 32% (15% to 51%) at 5 years. Overall survival (OS) was 91% (95% CI, 79% to 96%) at 1 year and 67% (50% to 79%) at 5 years. The most common National Cancer Institute grade 3 toxicities were neutropenic fever (59%), anorexia (21%), peripheral neuropathy (19%), orthostatic hypotension/vasovagal syncope (16%), and 1 patient failed to engraft. Compared with 26 MCL in CR1 historic controls treated with BEAM and ASCT, PFS was 85% and 43% for the BEAM group versus 87% and 57% for those who received bortezomib in addition to standard BEAM (V-BEAM) at 1 and 5 years, respectively (log-rank P = .37). OS was 88% and 50% for the BEAM group versus 96% and 72% for V-BEAM at 1 and 5 years, respectively (log-rank P = .78). In conclusion, V-BEAM and ASCT is feasible. The toxicities were manageable and we did not observe any treatment-related mortalities; however, we did observe an excess of autonomic dysfunction and ileus, which is concerning for overlapping toxicity with BEAM conditioning. Determining relative efficacy of V-BEAM compared to BEAM would require a randomized trial., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Low-grade follicular lymphoma (LGFL) is known to have a good prognosis. However, the clinical relevance of the presence and extent of diffuse growth areas within LGFL is not clear. Therefore, we studied 457 patients with nodal LGFL seen over a 20-year period (1982-2002). Relevant clinical and survival data were obtained and the pathology specimens were subclassified into predominantly follicular LGFL (>or=80% follicular areas), significantly follicular LGFL (30-70% follicular areas), significantly diffuse LGFL (<30% follicular areas) and pure diffuse follicle centre lymphoma (DFCL). The majority of the patients were treated with anthracycline-based regimens. Patients with DFCL were slightly older (median age, 67 years), more likely to have bulky disease (>5 cm), and often had suboptimal biopsies. However, no association was observed between the extent of diffuse areas and survival across the four subgroups. We conclude that the subclassification of LGFL based on the extent of diffuse areas does not have clinical relevance.

To compare the clinical outcomes of older (age > or =55 years) non-Hodgkin lymphoma (NHL) patients with younger NHL patients (<55 years) receiving autologous hematopoietic cell transplantation (HCT) while adjusting for patient-, disease-, and treatment-related variables, we compared autologous HCT outcomes in 805 NHL patients aged > or =55 years to 1949 NHL patients <55 years during the years 1990-2000 using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). In multivariate analysis, older patients with aggressive histologies were 1.86 times (95% confidence interval [CI] 1.43-2.43, P < .001) more likely than younger patients to experience treatment-related mortality (TRM). Relative death risks were 1.33 times (CI 1.04-1.71, P = .024) and 1.50 times (CI 1.33-16.9, P < .001) higher in older compared to younger patients with follicular grade I/II and aggressive histologies, respectively. Autologous HCT in older NHL patients is feasible, but most disease-related outcomes are statistically inferior to younger patients. Studies addressing supportive care particular to older patients, who are most likely to benefit from this approach, are recommended.

Purpose: Previous studies have evaluated practice variation in hematopoietic cell transplantation (HCT) among transplant centers and countries. There are no studies investigating individual physician practice variation in HCT., Methods: An international Internet-based survey of transplant physicians collected data on medical decisions made by adult and pediatric HCT physicians. Multivariable analyses identified practitioner and transplant center characteristics predictive of medical decision making., Results: Analysis of 526 assessable respondents showed a wide variation in management approaches to specific clinical scenarios. Pediatric and adult transplant physicians differed significantly in their management strategies for chronic myeloid leukemia, acute and chronic graft-versus-host disease, and choice of graft source for patients with aplastic anemia. Among adult transplant physicians, there was little agreement on the patient factors favoring reduced intensity conditioning or myeloablative conditioning., Conclusion: These results emphasize the heterogeneity of worldwide transplant practices. Local preferences or biases likely result in similar patients being offered different transplant and treatment procedures. The degree of practice variation also highlights the need for clinical trials to clarify areas of controversy. Where clinical trials are not feasible, data from observational studies may be the best available evidence to guide practice.

Between January 2001 and September 2005, 19 patients with progressive B-cell non-Hodgkin's lymphoma were treated with a cohort-specific dose of yttrium-90 ibritumomab tiuxetan (0.10 - 0.20 mCi/kg) to determine appropriate dosing in patients who had previously received high-dose chemotherapy and autologous stem cell transplantation (ASCT). Patients were required to have adequate end organ function and bone marrow status. Patients had been treated with a median of three prior therapies (range, 1 - 9). The median time from ASCT to radioimmunotherapy was 28 months. Hematologic toxicities were dose-limiting and included grade 3 - 4 thrombocytopenia (53%), neutropenia (32%), and anemia (21%). The majority of grade 3 - 4 events occurred at the 0.2 mCi/kg dose level. Nine patients responded (complete response, complete response unconfirmed, or partial response) to the therapy. At a median follow-up of 37 months, the 1-year event-free and overall survival rates were 26% and 57%, respectively. A dose of 0.2 mCi/kg ibritumomab tiuxetan is safe and effective for patients with progressive disease after high-dose chemotherapy and ASCT.

We evaluated the results of high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with diffuse aggressive non-Hodgkin lymphoma (NHL) in first relapse (Rel 1) or second complete remission (CR 2). Data were evaluated from the Autologous Blood and Marrow Transplant Registry on 429 patients with diffuse aggressive NHL who underwent transplantation in Rel 1 or CR 2. Transplantations were performed between 1989 and 1996 and were reported to the Autologous Blood and Marrow Transplant Registry by 93 centers in North and South America. The probability of 3-year survival was 44% (95% confidence interval [CI], 33%-55%). The probability at 3 years of progression-free survival was 31% (95% CI, 27%-36%). Patients who underwent transplantation in CR 2 had a 3-year probability of progression-free survival of 38% (95% CI, 30%-46%) compared with 28% (95% CI, 22%-33%) for those who were not in remission at the time of transplantation (P <.001). In multivariate analysis, chemotherapy resistance, increased lactic dehydrogenase at diagnosis, an interval of <12 months from diagnosis to relapse, age >or=40 years, and use of myeloid growth factors to accelerate posttransplantation bone marrow recovery were adverse predictors of survival. High-dose chemotherapy and autologous hematopoietic stem cell transplantation for patients with diffuse aggressive NHL in CR 2 or Rel 1 resulted in better outcome for patients with chemotherapy-sensitive disease, longer relapse-free intervals, and age <40 years. Exposure to myeloid growth factors to accelerate recovery for recipients of bone marrow grafts may increase the risk of disease progression or death.

Purpose: To compare results of syngeneic, allogeneic, and autologous hematopoietic stem-cell transplantation for non-Hodgkin's lymphoma (NHL)., Patients and Methods: The databases of the International Bone Marrow Transplant Registry (IBMTR) and the European Group for Blood and Marrow Transplantation were used to identify 89 NHL patients who received syngeneic transplants. These patients were compared with NHL patients identified from the IBMTR and the Autologous Blood and Marrow Transplant Registry who received allogeneic (T-cell depleted and T-cell replete) and autologous (purged and unpurged) transplants., Results: No significant differences in relapse rates were observed when results of allogeneic transplantation were compared with syngeneic transplantation for any histology. T-cell depletion of allografts was not associated with a higher relapse risk, but was associated with improved overall survival for patients with low-grade and intermediate-grade histology. Patients who received unpurged autografts for low-grade NHL had a five-fold (P =.008) greater risk of relapse than recipients of syngeneic transplants, and recipients of unpurged autografts had a two-fold (P =.0009) greater relapse risk than patients who received purged autografts. Among low-grade NHL patients, the use of purging was associated with significantly better disease-free survival (P =.003) and overall survival (P =.04) when compared with patients who received unpurged autografts., Conclusion: These analyses failed to find evidence of a graft-versus-lymphoma effect, but do provide indirect evidence to support the hypothesis that tumor contamination may contribute to lymphoma relapse, and that purging may be beneficial for patients undergoing autologous hematopoietic stem-cell transplantation for low-grade NHL.