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Many institutions have adopted algorithms based on preapheresis circulating CD34+ cell counts to optimize the use of plerixafor. However, a circulating peripheral blood CD34+ cell threshold that predicts mobilization failure has not been defined. The superiority of plerixafor + granulocyte colony-stimulating factor (G-CSF) over placebo + G-CSF for hematopoietic stem cell mobilization and collection was shown for patients with non-Hodgkin lymphoma in a phase III, prospective, randomized, controlled study. The question remains as to which patients may benefit most from the use of plerixafor. In this post hoc retrospective analysis, mobilization outcomes were compared between the 2 treatment arms in patients stratified by peripheral blood CD34+ cell count (<5, 5 to 9, 10 to 14, 15 to 19, or ≥20 cells/μL) obtained before study treatment and apheresis. Compared with placebo plus G-CSF, plerixafor plus G-CSF significantly increased the peripheral blood CD34+ cells/μL over prior day levels in all 5 stratified groups. The probability of subsequent transplantation without a rescue mobilization was far greater in the plerixafor-treated patients for the lowest initial (day 4) peripheral blood CD34+ cells/μL groups (<5, 5 to 9, or 10 to 14). Engraftment and durability were the same for the 2 treatment groups for all strata, but the effect in the lower strata could be altered by the addition of cells from rescue mobilizations. These findings may provide insight into the optimal use of plerixafor in all patients undergoing stem cell mobilization., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

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: Many institutions have adopted algorithms based on preapheresis circulating CD34+ cell counts to optimize the use of plerixafor. However, a circulating peripheral blood CD34+ cell threshold that predicts mobilization failure has not been defined. The superiority of plerixafor + granulocyte colony-stimulating factor (G-CSF) over placebo + G-CSF for hematopoietic stem cell mobilization and collection was shown for patients with non-Hodgkin lymphoma in a phase III, prospective, randomized, controlled study. The question remains as to which patients may benefit most from the use of plerixafor. In this post hoc retrospective analysis, mobilization outcomes were compared between the 2 treatment arms in patients stratified by peripheral blood CD34+ cell count (<5, 5 to 9, 10 to 14, 15 to 19, or ≥20 cells/μL) obtained before study treatment and apheresis. Compared with placebo plus G-CSF, plerixafor plus G-CSF significantly increased the peripheral blood CD34+ cells/μL over prior day levels in all 5 stratified groups. The probability of subsequent transplantation without a rescue mobilization was far greater in the plerixafor-treated patients for the lowest initial (day 4) peripheral blood CD34+ cells/μL groups (<5, 5 to 9, or 10 to 14). Engraftment and durability were the same for the 2 treatment groups for all strata, but the effect in the lower strata could be altered by the addition of cells from rescue mobilizations. These findings may provide insight into the optimal use of plerixafor in all patients undergoing stem cell mobilization. [Copyright &y& Elsevier]

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]

Abstract: To compare the clinical outcomes of older (age ≥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 ≥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. [Copyright &y& Elsevier]

Abstract: We studied the role of HLA-matched sibling hematopoietic cell transplantation (HCT) in treating t(8;21) acute myelogenous leukemia (AML) in first remission. Outcomes of 118 patients receiving HCT and reported to the Center for International Blood and Marrow Transplant Research were compared with 132 similar patients receiving chemotherapy selected from 8 German AML Intergroup multicenter trials. Characteristics of the cohorts were similar except that chemotherapy recipients were significantly older. To adjust for time to treatment bias, outcomes were compared using left-truncated Cox regression models. Transplants were associated with higher treatment-related mortality (TRM; relative risk [RR] 6.76, 95% confidence interval [CI] 2.95-15.45, P < .001), lower relapse (RR 0.47, 95% CI 0.25-0.85, P = .01), and similar relapse-free survival (P = .2). Loss of sex chromosomes (LOS) in addition to t(8;21) had a negative impact on overall survival (OS) in patients receiving chemotherapy. Patients without LOS experienced shorter survival after HCT comparing to chemotherapy (RR 3.05, P = .02), whereas patients with LOS had similar survival regardless of postremission therapy. In both cohorts, white blood cell count (WBC) at diagnosis >25 × 109/L was associated with a higher relapse risk (RR = 2.09, P = .03), lower relapse-free (RR = 1.9, P = .008), and OS (RR = 1.91, P = .01). In this cohort of patients with t(8;21) AML, HCT did not improve OS, because reduction of relapse was offset by high TRM. In the group without LOS, survival after chemotherapy was far superior to HCT. These results suggest that patients with t(8;21) AML without poor prognostic factors have higher rates of survival after chemotherapy as a post remission therapy compared to HCT. [Copyright &y& Elsevier]