This retrospective analysis suggests that marrow purging and posttransplant radiotherapy improve the outcome of patients with NHL autografted in first remission.
From September 1992 to January 1994, we evaluated the use of the CEPRATE SC stem cell concentrator (CellPro, Inc, Bothell, WA) to select CD34+ cells from the bone marrow (BM) of 25 patients with non-Hodgkin's lymphoma in complete remission. This system uses the biotinylated 12.8 IgM MoAb to select CD34+ cells. Cells are retained on an avidin column and detached by agitation. Fifteen patients have been transplanted with the CD34+ purified fraction. The CD34+ purified fraction of the 25 processed BMs contained a median of 0.54% of the original nucleated cells in a volume of 5 to 10 mL. The median concentration of CD34+ cells was 49% (range, 12% to 80%), and the median enrichment of CD34+ cells was 33-fold (range, 9- to 85-fold). This selected CD34+ fraction retained 60% (range, 15% to 95%) of late granulocyte-macrophage colony- forming units (CFU-GM), 55% (range, 12% to 99%) of early CFU-GM, and 31% (range, 2% to 100%) erythroid burst-forming units (BFU-E) corresponding to median enrichments of 22-fold (range, 1- to 71-fold), 19-fold (range, 2- to 58-fold), and 14-fold (range, 2- to 200-fold), respectively. There was a correlation between immune phenotypes and progenitor cells. In the initial buffy-coat fractions, the percentage of CD34+ cells was correlated to the cloning efficiency of both late CFU-GM (P < .05) and early CFU-GM (P < .001). In the final selected fraction, there was a correlation between the percentage of CD34+/CD33- and the cloning efficiency of early CFU-GM (P < .05) and between the percentage of CD34+/CD33+ and the cloning efficiency of late CFU-GM (P < .05). Lymphoma cells positive for t(14; 18) were found by polymerase chain reaction in 9 of 14 buffy coats tested before CD34+ cell purification. In 8 cases, the CD34(+)-selected fraction was found to be negative, and the CD34- fraction was found to be positive. After cryopreservation, the recoveries of progenitor cells in the CD34(+)- purified fraction were 79% for late CFU-GM, 71% for early CFU-GM, and 73% for BFU-E. The 15 patients transplanted with the concentrated CD34+ fraction received a median dose of 1 x 10(6) CD34+ cells/kg (range, 0.3 to 2.96) and 10.62 x 10(4) early CFU-GM/kg (range, 0.92 to 25.55). Median days to recovery to 0.5 x 10(9)/L neutrophils and 50 x 10(9)/L platelets were days 15 (range, 10 to 33) and 23 (range, 11 to 68), respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
Between January 1985 and July 1989 we diagnosed asymptomatic stage I multiple myeloma according to Durie and Salmon [Durie and Salmon: Cancer 36:842, 1975] in 91 patients. All patients were followed without chemotherapy. Disease progression occurred in 41 patients and the median time to progression for all patients was 48 months. In the Cox multivariate regression analysis, hemoglobin levels < 12 g/dl (P < .01), bone marrow plasmacytosis > 25% (P < .01), and M-component size > or = 30 g/l for Ig G or > or = 25 g/l for Ig A (P < .01) were the only significant prognostic factors for progression. The 38 patients without any harmful factor remained free of progression for a median of more than 50 months. The 18 patients with two or three of these characteristics (high-risk group) had the shortest median time to progression of 6 months. Despite different times to progression, the response rate and survival after chemotherapy were similar for all groups of patients. Patients in the high-risk group for progression have to be frequently monitored for disease progression and might benefit from early treatment.
A high remission rate is achieved with high-dose melphalan (HDM) in multiple myeloma (MM), and autologous transplantation of hematopoietic stem cells allows a prompt hematologic recovery after high-dose therapy. We treated 97 patients with high-risk MM (group 1:44 advanced MM including 14 primary resistances and 30 relapses; group 2: 53 newly diagnosed MM) with a first course of HDM. For responding patients a second course of high-dose therapy with hematopoietic stem cell support was proposed. After the first HDM, the overall response and complete remission rates were 71% and 25% with no significant difference between the two groups. The median durations of neutropenia and thrombocytopenia were significantly longer in group 1 (29.5 days and 32 days, respectively) than in group 2 (23 days and 17 days, respectively). This severe myelosuppression led to eight toxic deaths and the fact that only 38 of the 69 responders could proceed to the second course (three allogenic and 35 autologous transplantations). Among the 35 patients undergoing autologous transplantation (10 in group 1, 25 in group 2), 31 received their marrow unpurged collected after the first HDM, and four received peripheral blood stem cells. The median durations of neutropenia and thrombocytopenia after autologous transplantation were 24 days and 49 days, respectively. Two toxic deaths and nine prolonged thrombocytopenias were observed. The median survival for the 97 patients was 24 months (17 months in group 1, 37 months in group 2) and the median duration of response was 20 months. The only parameters that have a significant impact on the survival are the age (+/- 50 years) and the response to HDM. The median survival of the 35 patients undergoing autologous transplantation is 41 months, but the median duration of remission is 28 months with no plateau of the remission duration curve. Patients responding to HDM may have prolonged survival, but even a second course of high-dose therapy probably cannot eradicate the malignant clone.
Veno‐occlusive disease (VOD) is a major cause of toxic death after autologous bone marrow transplantation (ABMT). We studied the potential role of continuous administration of low‐dose heparin for VOD prevention in 234 consecutive patients who underwent ABMT in our institution. The population consisted of 98 patients autografted before October 1984 who did not receive heparin, and a series of 136 patients autografted from October 1984 to March 1989 containing 98 patients included in a randomized trial comparing heparin administration (n = 52) vs no heparin (n = 46), and an additional group of 38 patients who received non‐randomized heparin in view of high‐risk criteria to develop VOD (n = 31) or other reasons unrelated to VOD (n = 7). Overall, 90 patients (38%) received heparin and 144 (62%) did not. The global incidence of VOD was 13/234 (5–5%). Heparin did not reduce the risk of VOD in all subgroups studied. In particular, in the randomized trial, the incidence of VOD was 2.2% in the group without heparin vs 7–7% in the group receiving heparin. We analyzed in depth the 13 patients who developed VOD and we compared them to a control group of 13 patients pair‐matched for age, sex, diagnosis and preparative regimen, who did not develop VOD. We found that abnormal LFT before ABMT predisposed patients to VOD; refractoriness to platelet transfusion was observed in 85% of the patients in the VOD group vs 15% in the control group (p<0.05). VOD patients had an increased requirement for red cells and platelet transfusions, a lower recovery (R<25%) after the second and third platelet transfusion, and shorter intervals separating the first four platelet transfusions. Further, the platelet reconstitution after ABMT in the VOD group was slower in comparison to the control group (p<0.01). Again, in this pair‐matched analysis continuous infusion of low‐dose heparin did not prevent VOD.
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