Summary:In an effort to reduce the relapse rate after unpurged autologous bone marrow transplantation (ABMT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1), the standard conditioning regimens (cyclophosphamide/busulphan and cyclophosphamide/TBI) were intensified by adding idarubicin. Seventeen patients received a continuous infusion of 21 mg idarubicin/m 2 /day for 2 consecutive days in addition to the standard preparative regimen. Thirteen patients served as a historical control group. The 2-year disease-free survival (DFS) of 82% in the study group was significantly (P = 0.047) better compared to 46% DFS in the control group. The relapse rate (RR) was also significantly lower (7% vs 45%; P = 0.035) in the study group. The median time to reach a white cell count (WCC) of 0.5 × 10 9 /l was 20 days in the study group vs 17 days (P = NS) in the control group. The median time until recovery of the platelet counts to 20 × 10 9 /l was 152 days in the study group vs 57 days (P = NS) in the control group. The hypolasia in the study group resulted in a trend towards a higher need for transfusions: a median number of 38 units of erythrocytes vs 23 units in the control group (P = NS) and 23 units of platelet vs 18 units in the control group (P = NS). This pilot study suggests that addition of idarubicin to the standard conditioning regimens may improve DFS and overall survival (OS) of patients with AML treated with ABMT in CR1. These results should be confirmed in a prospective randomized study. Keywords: idarubicin; conditioning regimens; autologous bone marrow transplantation; acute myeloid leukemia; first complete remission A complete remission (CR) rate of 70-80% can be achieved in patients with newly diagnosed acute myeloid leukemia (AML) by currently used remission-induction regimens. Addition of a third drug such as etoposide, 1,2 replacement of daunorubicin by new anthracyclines such as idarubicin, [3][4][5] Correspondence: Dr Sh Jerjis, Division of Hematology, University Hospital St Radboud, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands Received 24 October 1997; accepted 14 February 1998 and high-dose cytarabine (HiDAC) 6,7 have improved the remission percentage of conventional regimens based on 3 days of daunorubicin and 10 days of standard-dose cytarabine. 8 Without further treatment almost all patients are expected to relapse. Only 10-15% of patients will be cured by using standard-dose consolidation and maintenance therapy. A higher DFS of 25-45% may be achieved after intensive consolidation chemotherapy. 9,10Allogeneic BMT as well as ABMT in de novo AML patients when performed during CR1 results in better DFS than intensive consolidation therapy [11][12][13] and greater antileukemic activity when performed in CR2. 14,15 Relapse is the main cause of death in hematologic malignancies after BMT, and even more so after ABMT. Combining the standard conditioning regimens (cyclophosphamide/busulphan and cyclophosphamide/TBI) with non-cross-resistant agents and selectin...
To evaluate factors affecting mobilisation and harvest and to calculate the economic costs of autologous stem cell transplantation in multiple myeloma (MM) we analysed 29 consecutive patients who had been transplanted at the Nijmegen University Hospital between January 1992 and February 1999. Thirteen patients had been treated with three or more melphalan cycles before transplantation (melphalan group), while four of the remaining 16 patients (no-melphalan group) had only received one melphalan cycle with an interval of one year or longer before harvest. The two groups were analysed for differences in mobilisation, harvest and the costs. Collection of a sufficient number of peripheral stem cells failed in 4 patients in the melphalan group, and these patients were transplanted with both bone marrow and peripheral stem cells. The greater need for growth factors (median 6,400 microg vs 4,500 microg) and the longer duration of admission (median 8 days vs 3 days) for mobilisation in the melphalan group increased significantly (p=0.01) the total mobilisation costs (median fl 13,876 vs fl 6,101). The greater number of apheresis sessions (median three) and the additional bone marrow harvests for patients who could not achieve a sufficient number of stem cells, increased significantly (p<0.001) the total harvest costs (median fl 9,690 vs fl 1,615) in the melphalan group. This resulted in significantly (p=0.008) higher overall costs of the procedure (median: fl 49,576 vs fl 35,889). The haematopoietic recovery of all groups was similar. The no-melphalan group was subdivided in two groups based on the median number of chemotherapy cycles before harvest. The heavily treated group had received more than 5 chemotherapy cycles and the moderately treated group four cycles or less. The median overall costs of these two groups were comparable (median fl 36,837 vs fl 34,351). This study suggests that the administration of stem cell toxic melphalan before harvest contributes to administration of more dosages of growth factor, longer admission duration for mobilisation and higher number of leukaphereses in order to collect sufficient number of stem cells. This resulted in significantly higher overall costs. More cycles of chemotherapy without melphalan did not increase significantly any studied parameter nor the total costs of procedure. Melphalan therapy or heavy pre-treatment did not prolong the repopulation interval, probably due to the infusion of similar number of progenitor cells.
We evaluated the costs of unpurged autologous stem cell transplantation in a non-randomised study of 54 consecutive patients with lymphoproliferative malignancies who have been transplanted at the Nijmegen University Hospital between July 1992 and March 1998. Thirty-five patients were transplanted with autologous peripheral stem cells (APSCT): 30 had non Hodgkin's lymphoma (NHL) and 5 acute lymphoblastic leukaemia (ALL). Nineteen patients were transplanted with autologous bone marrow stem cells (ABMT): 17 had NHL and 2 ALL. The number of progenitor cells (CFU-GM, BFU-E) and nucleated cells was significantly higher in peripheral blood transplants. The duration of cytopenia was shorter after APSCT. The leucocyte recovery to 0.5 x 10(9)/L was 13 days for recipients of peripheral stem cells compared to 20 days for bone marrow recipients (P <0.001). The platelet recoveries to 20 x 10(9)/L were 13 and 29 days, respectively (P = 0.001). This resulted in significantly shorter admission duration 24 days after APSCT versus 30 days (P = 0.003) after ABMT. Furthermore, a statistically significant difference between both groups was observed for antimicrobial costs (mean: fl 2,939 vs fl 4,888; P = 0.008), platelet transfusions (median: 3 vs 7 units; P = 0.01) and erythrocyte transfusions (median: 6 vs 10 units; P = 0.03). The mean overall costs were lower in patients transplanted with stem cells from peripheral blood: fl 34,178 versus fl 43,469 (P = 0.007). This study suggests that the APSCT results in significant cost savings due to shorter hospital stay and less costs of supportive care, despite higher mobilisation costs. The costs of blood transfusions and antimicrobials for patients with ALL were significantly higher when compared to patients with NHL.
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