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Tandem autotransplants are used to treat advanced testis cancer patients but their value compared to a single autotransplant is unknown. To evaluate the results of autotransplant in relapsed testicular/germ cell cancer, data from 300 patients undergoing autotransplants 1989-2002 were reported to the Center for International Blood and Marrow Transplant Research. We compared results for those patients intended to undergo tandem autotransplant procedures (N = 102) versus patients in whom a second autotransplant was not planned (N = 198). Five-year survival probability was 35% (95% confidence interval = 25%-46%) in the planned tandem transplant cohort compared to 42% (35%-49%) in the group not planned to have a second transplant (P = .29). Probability of progression-free survival at 5 years for these cohorts was 34% (25%-44%) and 38% (31%-45%), respectively (P = .50). The planned tandem autotransplant cohort had significantly more advanced disease at diagnosis and greater likelihood of cisplatin resistance. Patients intended to receive tandem transplants had a lower treatment-related mortality at 1 year (3% versus 10%, P = .02). Using propensity score analysis the planned tandem autotransplant cohort had significantly lower treatment-related mortality (P = .044) but no different risk of relapse (P = .541) compared to the planned single transplant cohort. Tandem autotransplants for testicular cancer are associated with less treatment-related mortality than a planned single transplant, with no differences in disease-related outcomes or overall survival at 3 years. Patient selection bias for either transplant approach, however, may affect the results of this observational study; a randomized trial is needed to determine which approach, if either, is better.

Granulocyte colony-stimulating factor (G-CSF) is often administered after hematopoietic-cell transplantation (HCT) to accelerate neutrophil recovery, but it is unclear what impact G-CSF has on long-term transplantation outcomes. We analyzed within the database of the Center for International Blood and Marrow Transplant Research the impact of giving posttransplantation G-CSF on the outcomes of allogeneic HCT for acute myelogenous leukemia and chronic myelogenous leukemia in 2719 patients who underwent transplantation between 1995 and 2000. These included 1435 recipients of HLA-identical sibling bone marrow (BM), 609 recipients of HLA-identical peripheral-blood stem cells (PBSCs), and 675 recipients of unrelated donor BM transplants. Outcomes were compared between patients receiving or not receiving G-CSF within 7 days of HCT according to graft type. Median follow-up was more than 30 months (range, 2-87 months). G-CSF shortened the posttransplantation neutropenic period, but did not affect days +30 and +100 treatment-related mortality (TRM). Probabilities of acute and chronic graft-versus-host disease (GVHD), leukemia-free survival (LFS), and overall survival were similar whether or not G-CSF was given. Multivariate analyses confirmed that giving G-CSF did not affect the risk of GVHD, TRM, LFS, or survival. In conclusion, results of this study found no long-term benefit or disadvantage of giving G-CSF after transplantation to promote hematopoietic recovery.

Although donation of bone marrow (BM) or peripheral blood stem cells (PBSCs) from children to family members undergoing allogeneic transplantation are well-established procedures, studies detailing levels of pain, symptoms, and long-term recovery are lacking. To address this lack, we prospectively enrolled 294 donors age 20% of females and males age 13 to 17 years do not return to baseline pain levels by 1 year after BM donation. Studies aimed at decreasing symptoms and improving recovery in older children are warranted.

The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study. RDs aged > 60 had a lower median CD34+ level before apheresis compared with younger RDs (age > 60, 59 × 106/L; age 41 to 60, 81 × 106/L; age 18 to 40, 121 × 106/L; P < .001). This resulted in older donors undergoing more apheresis procedures (49% versus 30% ≥ 2 collections, P < .001) and higher collection volumes (52% versus 32% > 24 L, P < .001), leading to high percentages of donors aged > 60 with postcollection thrombocytopenia

Pre-transplant PET/CT may be prognostic in diffuse large B-cell lymphoma (DLBCL) patients undergoing autologous stem cell transplantation (ASCT). We reviewed relapsed and pre-transplant PET/CT scans of 32 patients with DLBCL treated with ASCT to determine the Deauville score and the maximum standardized uptake value (SUVmax). Patients with a Deauville score of 4 had a significantly inferior prognosis. The 3-year progression-free survival (PFS) for patients with Deauville 1-3 score was 64%, compared to 0% for Deauville 4, while the 3-year overall survival (OS) was 84% and 25%, respectively (p < .001, p = .002). The change in the SUVmax (>66 versus ≤66%) was not predictive of PFS or OS, but a high pre-transplant SUVmax (>6) demonstrated a trend towards an inferior PFS. Pre-transplant PET/CT is a tool for identifying DLBCL patients at high risk for treatment failure with ASCT and could be used to risk-stratify patients in prospective clinical trials of novel transplant strategies. [ABSTRACT FROM AUTHOR]

Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone combined with cytarabine and methotrexate) is an intense chemotherapy regimen frequently used for hematologic malignancies including mantle cell lymphoma. To address whether treatment with hyper-CVAD impairs mobilization of peripheral blood stem cells, we retrospectively analyzed mobilization data from 77 consecutive adult patients with mantle cell lymphoma who underwent peripheral blood stem cell (PBSC) mobilization for planned autologous stem cell transplant (ASCT). Compared to patients treated with alternative regimens, patients treated with hyper-CVAD collected fewer CD34++ cells, required more total days of pheresis, and more frequently required a second mobilization attempt, despite being more likely to have undergone mobilization with a VP16-containing regimen. In multivariable linear regression analysis, treatment with hyper-CVAD was associated with a significant reduction in total CD34++ cells mobilized ( p < 0.001). These findings suggest that alternative mobilizing strategies prior to ASCT are needed for patients with mantle cell lymphoma who have received hyper-CVAD. [ABSTRACT FROM AUTHOR]

High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the preferred treatment modality for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). To assess long-term outcomes of these patients, we retrospectively analysed data from 309 consecutive patients who underwent ASCT for DLBCL between 1994 and 2006. We found that non-relapse mortality (NRM) became the major cause of death beginning approximately 8 years after ASCT. The most common causes of NRM during the study period were respiratory failure (31%), infection (13%), cardiac toxicity (15%) and secondary malignancy (15%). The strongest predictor of relapse mortality (RM) was disease status at transplant: patients who were in second or greater complete or partial remission had a higher risk of RM than those in first complete or partial remission [hazard ratio (HR) 3·7, P < 0·001], as did those who were relapsed or refractory (HR 4·9, P < 0·001). We describe the longest reported follow-up of a large cohort of DLBCL patients uniformly-treated with ASCT. Although relapse was initially the more likely cause of death, NRM exceeded RM after 8 years. After ASCT, surviving patients have significantly increased risk mortality rates relative to the general population and this excess risk persists over time. [ABSTRACT FROM AUTHOR]

Transformed lymphoma (TL) is historically associated with a poor prognosis, though autologous stem cell transplantation (ASCT) has been applied successfully. Better patient selection is needed for this intensive therapy. We analyzed the outcomes between de novo and transformed large B-cell lymphoma in patients undergoing ASCT, with regard to the immunohistochemical (IHC) features of potential prognostic utility including CD10, BCL6, MUM-1, Ki67, and BCL2. Of all patients undergoing ASCT for large B-cell lymphoma at the Cleveland Clinic Taussig Cancer Institute between 2003 and 2008, 56 patients (31 de novo and 25 TL) had undergone detailed IHC analysis. Three-year relapse-free-survival (RFS) and overall survival (OS) for TL vs. patients with de novo large B-cell lymphoma were 64%vs. 59% and 63%vs. 59%, respectively. More patients with TL were characterized as germinal-center B cell-of-origin (92%) than patients with de novo large B-cell lymphoma (71%). Immunohistochemistry did not predict relapse-free or overall survival, and ASCT afforded a high rate of PFS in patients with TL. [ABSTRACT FROM AUTHOR]

High-dose busulfan (Bu) is an integral component of commonly used preparative regimens for both allogeneic and autologous transplantation. There is significant interest in comparing the efficacy and toxicity of administering Bu every 6 (Bu6) or every 24 hours (daily Bu). To facilitate a therapeutic dose-monitoring protocol, we transitioned from Bu6 to daily Bu dosing for patients with Hodgkin and non-Hodgkin lymphoma undergoing autologous stem cell transplantation (ASCT). Here, we retrospectively review outcomes of 400 consecutive eligible lymphoma patients who underwent ASCT from 2007 to 2013 with high-dose busulfan (Bu), cyclophosphamide (Cy), and etoposide (E). Bu was given at a fixed dose of either .8 mg/kg every 6 hours for 14 doses for 307 patients or a fixed dose of 2.8 mg/kg every 24 hours for 4 doses (days −9 through −6) for 93 patients who underwent transplantation after the transition from Bu6 to daily Bu was made. Toxicity was assessed using pulmonary and liver function tests (LFT) at specified time points before and after ASCT. Baseline patient and disease characteristics of patients dosed with Bu6 and daily Bu were similar. There was no significant difference in forced expiratory volume in 1 second or diffusing capacity of the lungs for carbon monoxide before and after transplantation in the Bu6 versus daily Bu cohorts. Changes in LFTs with daily Bu were not significantly different than those with Bu6. There were no differences in relapse, nonrelapse mortality, progression-free survival, or overall survival between Bu6 and Bu 24 administration schedules in univariable or multivariable analysis ( P  ≥ .34). For a subset of 23 patients who had first-dose Bu levels measured, we observed significant variation in an median estimated cumulative area under the curve (AUC) of 17,568 µM-minute (range, 12,104 µM-23,084 µM-minute). In conclusion, daily Bu with Cy/E is more convenient than Bu6, has equivalent outcomes, and results in no increase in either hepatic or pulmonary toxicity. Consistent with previous reports, there is a significant range of Bu AUC levels, with a standard deviation of 13%. These data provide rationale for our prospective clinical trial of real-time therapeutic dose monitoring of Bu. [ABSTRACT FROM AUTHOR]

Autologous hematopoietic stem cell transplantation (ASCT) is an established treatment for patients with hematologic malignancies, yet the impact of transplanted CD34+ cell dose on clinical outcomes is unresolved. We conducted post hoc analyses of transplanted CD34+ cell dose and hematopoietic recovery following ASCT in 438 patients with non-Hodgkin lymphoma (NHL) or multiple myeloma (MM), using data from 2 multicenter phase 3 clinical studies that compared plerixafor plus granulocyte-colony stimulating factor (G-CSF) versus placebo plus G-CSF as stem cell mobilization regimens. Days to engraftment and the proportion of patients who reached predetermined blood count thresholds were compared across 3 CD34+ cell dose levels: 2-4 × 106 cells/kg, 4-6 × 106 cells/kg, and >6 × 106 cells/kg, regardless of mobilization treatment. Short-term neutrophil and platelet engraftment times were similar regardless of cell dose. A significant linear trend was observed between transplanted CD34+ cell dose and the proportion of patients with platelet count >150 × 109/L at 100 days (P < .001), 6 months (P = .026), and 12 months (P = .020) in patients with NHL, and at 100 days in patients with MM (P = .004). A linear trend was also observed between transplanted cell dose and the proportion of patients with platelet count >100 × 109/L at 100 days (P < .001) and 6 months (P = .023) in patients with NHL. A higher cell dose was associated with a lower percentage of NHL patients requiring red blood cell transfusions (P = .006). Our analyses confirm previous findings that transplanted CD34+ cell dose may be associated with better long-term platelet recovery after ASCT. [Copyright &y& Elsevier]

The poor prognosis of patients with prolymphocytic leukemia (PLL) has led some clinicians to recommend allogeneic hematopoietic cell transplant (HCT). However, the data to support this approach is limited to case-reports and small case series. We reviewed the database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to determine outcomes after allotransplant for patients with PLL. We identified 47 patients with a median age of 54 years (range: 30-75 years). With a median follow-up of 13 months, progression-free survival (PFS) was 33% (95% confidence interval [CI] 20%-47%) at 1 year. The most common cause of death was relapse or progression in 49%. The cumulative incidence of treatment-related mortality (TRM) at 1-year posttransplant was 28%. The small patient population prohibited prognostic factor analysis, but these data support consideration of allotransplant for PLL. Further study of a larger population of patients is needed to determine which patients are more likely to benefit. [Copyright &y& Elsevier]

Myelofibrosis is a myeloproliferative disorder incurable with conventional strategies. Several small series have reported long-term disease-free survival (DSF) after allogeneic hematopoietic cell transplantation (HCT). In this study, we analyze the outcomes of 289 patients receiving allogeneic transplantation for primary myelofibrosis between 1989 and 2002, from the database of the Center for International Bone Marrow Transplant Research (CIBMTR). The median age was 47 years (range: 18-73 years). Donors were HLA identical siblings in 162 patients, unrelated individuals in 101 patients, and HLA nonidentical family members in 26 patients. Patients were treated with a variety of conditioning regimens and graft-versus-host disease (GVHD) prophylaxis regimens. Splenectomy was performed in 65 patients prior to transplantation. The 100-day treatment-related mortality was 18% for HLA identical sibling transplants, 35% for unrelated transplants, and 19% for transplants from alternative related donors. Corresponding 5-year overall survival (OS) rates were 37%, 30%, and 40%, respectively. DFS rates were 33%, 27%, and 22%, respectively. DFS for patients receiving reduced-intensity transplants was comparable: 39% for HLA identical sibling donors and 17% for unrelated donors at 3 years. In this large retrospective series, allogeneic transplantation for myelofibrosis resulted in long-term relapse-free survival (RFS) in about one-third of patients. [Copyright &y& Elsevier]

Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens to treat diffuse large B cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, however, many patients develop refractory or recurrent DLBCL and then undergo autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes after AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n = 176; +R cohort) or was not (n = 818; −R cohort) administered with front-line or salvage therapy before AuHCT. The +R cohort had superior progression-free survival (PFS; 50% vs 38%; P = .008) and overall survival (OS; 57% vs 45%; P = .006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Nonrelapse mortality (NRM) did not differ significantly between the 2 cohorts. In multivariate analysis, the +R cohort had improved PFS (relative risk of relapse/progression or death, 0.64; P < .001) and improved OS (relative risk of death, 0.74; P = .039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival after AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM. [Copyright &y& Elsevier]

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only known curative therapy for chronic myelogenous leukemia (CML). Failure, because of relapse or nonrelapse mortality (NRM), generally occurs within 3 years of transplantation, but large studies with long-term follow-up are limited. We present mature results in 335 patients with CML who underwent allogeneic bone marrow transplantation (BMT) from HLA-identical siblings following busulfan and cyclophosphamide (BU/Cy2). Two hundred twenty-nine were in chronic phase (CP) and 106 in accelerated or blastic phase at transplantation. Median follow-up exceeded 14 years. The estimated probability of 18-year leukemia-free survival (LFS) for CP patients was 55.6% and for those beyond CP, 10.5%. Of 182 patients who survived leukemia-free at 3 years, the estimated probability of LFS at 18 years was 61.9%. Late relapse (P = .039) and late NRM (P = .008) occurred at higher rates in patients beyond CP at transplantation. There was no plateau in LFS. [Copyright &y& Elsevier]