Peripheral Blood Stem Cell Transplantation During Postremission Treatment of de Novo Acute Myelogenous Leukemia
Intensification of induction and consolidation treatment in de novo AML lead to a continuous improvement of disease-free survival in the last 20 years. To increase dose-intensity during consolidation, patients in continued CR (n = 16) which did not qualify for allogeneic BMT, received busulfan/cyclophosphamide conditioning and peripheral blood stem cell transplantation (PBSCT) after double induction treatment with TAD (thioguanine, daunorubicin and AraC) and HAM (high-dose AraC and mitoxantrone) and an early consolidation with a second course of TAD. G-CSF treatment was started on day two after each chemotherapy as well as on the day of PBSCT. PBSC were collected after mobilization with HAM for back-up and after the second course of TAD for transplantation. PBSCT could be performed in all patients being in continued CR (1.33 × 106 CD34+ cells per kg (range 1.0 to 2.9 × 106); 1.38 × 105 CFU-GM/kg (range 0.14 to 2.8 × 105)) except one patient with persistent pancytopenia after the second course of TAD. A further mobilization with cyclophosphamide was necessary in three patients after the second course of TAD. Leukocyte counts of 109/1 were achieved within 10.4 days (range 8–12). In five cases the increase in thrombocyte counts was biphasic but remained stable > 100 × 109/1 after 59 days (range 16–92) in all patients. Severe toxicities (grade IV) were observed in 4 patients (peumonia 2 ×, pericarditis 1 ×, VOD 1 ×). One patient died of pneumonia. Relapse-free survival was 66% (95% confidence interval 58 to 74%) at a mean observation time of 27 months. Cytogenetically patients were found to be at good (n = 1) intermediate (n = 14) and high risk (n = 1). Of the four patients relapsing three only achieved CR after a second induction cycle, one was at high risk cytogenetically and two had an excessively high initial LDH level (> 1000 U/l). One patient developed a myelodysplastic syndrome. Thus, myeloablative chemotherapy with PBSCT has tolerable toxicity and may be performed routinely as consolidation treatment following TAD-HAM-TAD. The risk of relapse seems to be increased if achievement of CR is delayed. The observed relapse-free survival justifies a randomized trial with standard versus high-dose chemotherapy combined with the transplantation of in vivo purged PBSCs.
KeywordsLeukemia Pneumonia Glutamine Bilirubin Neutropenia
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- 1.Reichle A, Andreesen R (1998) Myeloablative chemotherapy and peripheral blood stem cell transplantation vs consolidation therapy of acute myelogenous leukemia in first remission. In: Acute leukemia VII, in pressGoogle Scholar
- 2.Büchner T, Hiddemann W, Wörmann B (1992) Longterm effects of prolonged maintenance and of very early intensification chemotherapy in AML: data from AMLCG. Leukemia 6 Suppl 2: 68–71Google Scholar
- 3.Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, Bradstock K, Enno A, Wolf MM, Fox R, Cobcroft R, Herrmann R, Van Der Weyden M, Lowenthal RM, Page F, Garson OM, Juneja S (1996) A randomized study of high dose cytara-bine in induction in acute myeloid leukemia. Blood 87: 1710–1717PubMedGoogle Scholar
- 7.Biichner-T, Hiddemann-W, Schaefer-UW, Lof-fler-H, Maschmeyer-G, Ludwig-WD, Aul-C, La-than-B, Heinecke-A (1992) Combined effect of very early intensification and prolonged post-remission chemotherapy in patients with AML. Leukemia 6 Suppl 4: 68–70Google Scholar
- 11.Sanz MA, de la Rubia J, Sanz GF, Martin G, Martinez J, Jarque I, Sempere A, Gomis F, Senent L, Soler MA (1993) Busulfan plus cyclophosphamide followed by autologous blood stem cell transplantation for patients with acute myeloblasts leukemia in first complete remission: a report from a single institution. J Clin Oncol 11: 1661–1667PubMedGoogle Scholar
- 12.Lévy V, Rio B, Belhocine R (1996) Autologous stem cell transplantation (APSCT) with G CSF primed peripheral blood in acute myelogenous leukemia (AML) in first remission (CR). Blood 88: 238bGoogle Scholar
- 13.Schiller G, Mittal Henkle A, Lill M (1995) Transplantation of autologous blood progenitor cells procured after high dose cytarabine/G CSF based consolidation for adults with acute myelogenous leukemia in first remission. Blood 86: 99aGoogle Scholar
- 14.Linker CA, Ries CA, Damon LE (1995) Autologous stem cell transplantation for acute myeloid leukemia in first remission. Blood 86: 99aGoogle Scholar