Summary:with median survivals of 3.0 and 10.5 months for nonHodgkin's lymphoma (NHL) and Hodgkin's disease (HD), respectively. 1Increasing numbers of patients have received autologous stem cell transplants (ASCT) for hematologic maligPotential benefits of allogeneic bone marrow transplantation (alloBMT) over ASCT include lack of graft tumor nancies. Since only a fraction of these patients are cured, physicians are more frequently faced with the contamination and the presence of a graft-versus-tumor effect. The graft-versus-leukemia effect is well established dilemma of how to manage relapse post-transplant. Potential advantages of allogeneic transplantation in alloBMT. 2 There is a significantly lower incidence of leukemia relapse in patients who undergo alloBMT com-(alloBMT) over ASCT include lack of graft tumor contamination and presence of a graft-versus-tumor effect.pared to patients who receive autografts. Evidence of a graft-versus-lymphoma effect has also been demonstrated For this reason, patients who relapse after ASCT are often considered candidates for allogeneic bone marrow in patients who received alloBMT for treatment of lymphoid malignancies. 3 Therefore, there is a theoretical benefit transplantation. However, there is limited knowledge on the outcome of alloBMT in patients who relapse after for patients who relapse after ASCT to receive subsequently an alloBMT. However, there is limited data on ASCT. We retrospectively analyzed the outcome of 20 patients with malignant lymphoma (n = 14) and AML the outcome of patients who undergo alloBMT for relapse after ASCT. (n = 6) who underwent alloBMT after failing an ASCT. The median age was 30 (17-41) years and the intervalThe purpose of this study was to evaluate therapy-related toxicities, long-term survival, and hematopoietic stem cell from ASCT to alloBMT was 10.5 (2-25) months. Seventeen patients died between 0.3 to 11 months (median engraftment in patients with hematologic malignancies who underwent alloBMT for progressive disease after ASCT. 2.0) after alloBMT, all due to BMT-related toxicities. Three patients remain alive and free of disease at 1.1, and 2.5 years after alloBMT. Sixteen of the 18 evaluable patients (89%) developed grade II-IV acute Materials and methods GVHD. Patients undergoing alloBMT after ASCT have a very high treatment-related mortality and incidence of Study cohort grade II-IV acute GVHD. Alternative treatments with salvage chemotherapy, radiation or investigationalWe retrospectively analyzed consecutive patients who underwent alloBMT after failing an ASCT for hematologic approaches should be considered in patients who relapse after ASCT.malignancies, from 1988 to 1995, at the following institutions: University of Texas Health Science Center at San Keywords: BMT; relapse; second transplant; lymphoma; leukemia Antonio (San Antonio, TX), Vanderbilt University (Nashville, TN), University of Oklahoma Health Science Center (Oklahoma City, OK), University of California at Los Angeles School of Medicine (Los Angeles, CA), and High-...
PBSC are the preferred source of stem cells for autologous transplantation. However, regardless of the mobilization procedure used, 10%-20% of patients fail to collect an adequate number to ensure prompt engraftment. There is as yet no standard mobilization procedure for patients who fail a first mobilization attempt. Here, we describe a highly efficient strategy to obtain an adequate number of stem cells for patients who failed a first mobilization attempt. Seventy-four patients with various hematologic malignancies underwent initial mobilization with various regimens including hematopoietic growth factors with or without chemotherapy. In 72% of patients, > or =2 x 10(6) CD34+ stem cells/kg were collected in the initial mobilization attempt, and patients engrafted in a median of 10 days for neutrophils and 12 days for platelets. Eighteen patients failed to mobilize adequate numbers of stem cells, defined as the inability to collect 0.2 x 10(6) CD34+ stem cells/kg/day in the first 2-3 days. These patients had their apheresis halted. Patients were immediately given G-CSF (32 microg/kg/day) for 4 days as a second attempt at mobilization. Eighty-eight percent of these patients achieved the target of > or =2 x 10(6) CD34+ cells/kg, with a median duration of apheresis of 5 days (including the first and second mobilizations). The mean CD34+ cells/kg/day increased after administration of high-dose G-CSF from 0.16 after the first mobilization attempt to 0.61 (p = 0.0002) after the second mobilization. All patients engrafted in a median of 11 and 13 days for neutrophils and platelets, respectively. We conclude that patients whose apheresis yield is <0.4 x 10(6) CD34+ cells/kg after the first two apheresis collections can be successfully mobilized if high-dose G-CSF is administered immediately and continued until achieving > or =2 x 10(6) CD34+ stem cells/kg.
We designed a randomized, prospective three-arm mobilization study to determine the kinetics of peripheral blood stem cell (PBSC) mobilization in 60 non-Hodgkin's lymphoma (NHL) patients primed with cyclophosphamide (CTX) in combination with granulocyte colony-stimulating factor (G-CSF) (arm A), granulocyte-macrophage (GM)-CSF (arm B) or GM-CSF/G-CSF (arm C). We also compared mobilization and transplant-related toxicities, pre- and post-transplant support and the probability of survival among the three arms. To date, 35 patients have been enrolled in the study; 13 patients have been enrolled in arm A, 10 patients in arm B, and 13 patients in arm C. Successful collection of the target of > or = 2 X 10(6) CD34+ cells/kg in one to four apheresis collections was 10/13, 6/10, and 7/12 in arms A, B, and C, respectively. The differences between arms were not statistically significant. The median time to achieve the target CD34+ cells in patients who successfully mobilized the target CD34+ cells was 3 days, 2 days, and 1 day, in patients in arms A, B, and C, respectively. The time for neutrophil engraftment was 11, 10, and 10 days in arms A, B, and C, respectively. The time for platelet engraftment was 11 days for patients in all arms of the study. Most importantly, no significant differences were observed among the three arms in the duration of neutropenic fever, the extent of mucositis, diarrhea, and nausea/vomiting, or in the number of units of platelets or red cells transfused after transplantation. Risk factors associated with poor mobilization were > or = 3 regimens of chemotherapy prior to mobilization, older age, and disease histology (follicular versus diffuse). Therefore, we conclude that the type of growth factor used for mobilization did not play a major role in the outcome of mobilization and recommend mobilizing NHL patients before they receive multiple regimens of chemotherapy.
Paclitaxel and G-CSF have been evaluated for HPC mobilization in breast cancer and found to have tolerable toxicity with a predictable time to initiate leukapheresis. However, this approach has not been reported in patients with hematologic malignancies failing prior mobilization. We report a case-series of 26 adults given paclitaxel and G-CSF for HPC mobilization after failure of an initial mobilization. Patients received paclitaxel 250 mg/m(2) followed by G-CSF 10-16 mcg/kg/day. Compared to the initial regimen, paclitaxel mobilization produced greater CD34+ cell yields (median 1.53 x 10(6) CD34+ cells/kg vs. 0.79 x 10(6) CD34+ cells/kg, p = 0.004). Seventy-six percent of patients initiated leukapheresis on day 8, the remainder on day 9 or 10. Three patients developed febrile neutropenia resulting in one death prior to leukapheresis. Overall, 73% of patients proceeded with autologous HPC transplant. This case-series suggests paclitaxel may be an option for HPC mobilization in patients failing prior regimens.
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