Farzaneh Maadani

Concurrent Administration of High-Dose Rituximab Before and After Autologous Stem-Cell Transplantation for Relapsed Aggressive B-Cell Non-Hodgkin’s Lymphomas

PURPOSE We investigated the efficacy and safety of administering high-dose rituximab (HD-R) in combination with high-dose carmustine, cytarabine, etoposide, and melphalan chemotherapy and autologous stem-cell transplantation (SCT) in patients with recurrent B-cell aggressive non-Hodgkins lymphoma (NHL). PATIENTS AND METHODS Sixty-seven consecutive patients were treated. Rituximab was administered during stem-cell mobilization (1 day before chemotherapy at 375 mg/m(2) and 7 days after chemotherapy at 1,000 mg/m(2)), together with granulocyte colony-stimulating factor 10 mug/kg and granulocyte-macrophage colony-stimulating factor 250 microg/m(2) administered subcutaneously daily. HD-R of 1,000 mg/m(2) was administered again days 1 and 8 after transplantation. The results of this treatment were retrospectively compared with those of a historical control group receiving the same preparative regimen without rituximab. RESULTS With a median follow-up time for the study group of 20 months, the overall survival rate at 2-years was 80% (95% CI, 65% to 89%) for the study group and 53% (95% CI, 34% to 69%) for the control group (P = .002). Disease-free survival was 67% (95% CI, 51% to 79%) for the study group and 43% (95% CI, 26% to 60%) for the control group (P = .004). The median time to recovery of absolute neutrophil count to >/= 500 cells/microL was 11 days (range, 8 to 37 days) for the rituximab group and 10 days (range, 8 to 17 days) for the matched control group (P = .001). However, infections were not significantly increased in patients treated with rituximab. CONCLUSION The results of this study suggest that using HD-R and autologous SCT is a feasible and promising treatment for patients with B-cell aggressive NHL.

Nonmyeloablative Allogeneic Hematopoietic Transplantation: A Promising Salvage Therapy for Patients With Non-Hodgkin's Lymphoma Whose Disease Has Failed a Prior Autologous Transplantation

PURPOSE Allogeneic transplantation for patients with lymphoma who experience a recurrence after an autologous transplantation has been considered a hazardous therapeutic choice. We investigated the safety and efficacy of nonmyeloablative stem-cell transplantation in these patients. PATIENTS AND METHODS Patients were required to have chemosensitive or stable disease. Twenty consecutive patients were treated in two sequential trials. Fifteen patients underwent a preparative regimen of fludarabine (30 mg/m(2) daily for 3 days), intravenous cyclophosphamide (750 mg/m(2) daily for 3 days), and rituximab. For the remaining five patients, the conditioning regimen consisted of cisplatin (25 mg/m(2) continuous infusion daily for 4 days), fludarabine (30 mg/m(2) daily for 2 days), and cytarabine (1,000 mg/m(2) daily for 2 days). Tacrolimus and methotrexate were used for graft-versus-host disease prophylaxis. RESULTS All patients experienced engraftment of donor cells. One patient (5%) experienced grade 2 acute graft-versus-host disease, and no patients experienced a higher grade. One patient experienced disease progression at 115 days post-transplantation and responded to donor lymphocyte infusion. The remaining patients remained disease-free. One patient died at 10.5 months from a fungal infection. With a median follow-up time of 25 months, the estimated 3-year current progression-free survival rate was 95%. CONCLUSION These data suggest that nonmyeloablative allogeneic stem-cell transplantation is an effective option in lymphoma patients with chemosensitive or stable disease who experience disease recurrence following autologous transplantation.

Allogeneic stem-cell transplantation in patients with cutaneous lymphoma: updated results from a single institution

BACKGROUND Cutaneous T-cell lymphomas (CTCLs) and its common variants mycosis fungoides (MF) and leukemic Sézary syndrome (SS) are rare extranodal non-Hodgkins lymphomas. Patients who present with advanced disease and large-cell transformation (LCT) are incurable with standard treatments. In this article, we report the largest single-center experience with allogeneic stem-cell transplantation (SCT) for advanced CTCL. PATIENTS AND METHODS This is a prospective case series of 47 CTCL patients who underwent allogeneic SCT after failure of standard therapy between July 2001 and September 2013. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) curves. The method of Fine and Gray was used to fit regression models to the same covariates for these cumulative incidence data. RESULTS The Kaplan-Meier estimates of OS and PFS at 4 years were 51% and 26%, respectively. There was no statistical difference in the OS in patients who had MF alone, SS, MF with LCT, or SS with LCT. PFS at 4 years was superior in patients who had SS versus those who did not (52.4% versus 9.9%; P = 0.02). The cumulative incidences of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD were 40% and 28%, respectively. The cumulative nonrelapse mortality rate was 16.7% at 2 years. CONCLUSION Allogeneic SCT may result in long-term remissions in a subset of patients with advanced CTCL. Although post-SCT relapse rates are high, many patients respond to immunomodulation and achieve durable remissions. CLINICALTRIALSGOV NCT00506129.

Identification of megakaryocyte precursors in peripheral blood stem cell collections from normal donors

Platelet engraftment, the time course and magnitude of platelet recovery (PR) post‐transplant, is imprecisely defined but is most often reported as the time to transfusion (tx) independence and/or a platelet count ⩾20,000/μl. While correlations between engraftment time for granulocytes (PMN) and the dose of CD34‐positive cells per kilogram are established, such associations have not been established for platelet engraftment. The objective of this study was to quantify subpopulations of CD34‐positive cells in peripheral blood stem cell (PBSC) collections of normal, colony‐stimulating factor‐granulocyte) (G‐CSF) primed donors that might represent megakaryocyte (MK) precursors, and to determine whether there is a statistical association between the dose transfused and the time course of the recovery. Based on previously published data of the sequential expression of CD34, HLA‐DR, and CD61, among others, during MK maturation, a combination of corresponding antibodies for the detection of various antigen coexpressions by flow cytometry fluorescence‐activated cell sorting [FACS] was chosen. CD34‐positive cells were further subdivided into CD34++ (bright) and + (dim). Ploidy of density‐gradient separated cells was examined in subsequent donor samples by FACS.

Patient age and number of apheresis days may predict development of secondary myelodysplastic syndrome and acute myelogenous leukemia after high-dose chemotherapy and autologous stem cell transplantation for lymphoma

The goal of our study was to find predictors for the development of secondary myelodysplastic syndrome or acute myelogenous leukemia (s‐MDS/AML) in patients with relapsed or refractory lymphoma who received high‐dose chemotherapy and autologous stem cell transplantation (ASCT).