High-dose melphalan is an effective salvage therapy in acute myeloid leukaemia patients with refractory relapse and relapse after autologous stem cell transplantation.
In a pilot study high-dose melphalan (HD-Mel, 200 mg/m2) and autologous stem cell transplantation (ASCT) were administered to 14 patients (median age 52, range 29-60 years) with acute myeloid leukaemia (AML) in first relapse after a previous ASCT in first complete remission (n=11) or chemotherapy (n=3). A first cohort of five patients received HD-Mel as salvage therapy after a previous cycle of mitoxantrone, topotecan and cytarabine (MTC) had failed in four out of five patients, while a second cohort of nine patients received HD-Mel in untreated relapse. Thirteen (93%) of 14 patients achieved a second complete remission (CR2), including all four patients who had been refractory to MTC. No treatment-related mortality was observed after HD-Mel. Thirteen (93%) patients were able to proceed to a dose-reduced allogeneic stem cell transplantation (allo-SCT) from human-leucocyte-antigens-compatible unrelated (n=12) or sibling donors (n=1) in CR2 (n=11) or poor recovery/relapse (n=2) after a median of 2 (1.7-4.5) months following HD-Mel. Three MTC-refractory patients, but none of the upfront HD-Mel patients, died due to an allograft-related non-relapse cause. Nine patients are alive in CR2 after a median of 6 (2-49) months after HD-Mel and a median of 4 (0.6-47) months after a sequential allo-SCT. Although median follow-up is still short, the proportion of patients achieving a CR2, as well as of those proceeding to a subsequent reduced-intensity-conditioning-allo-SCT, is superior to those previously reported. Our results highly encourage to further investigate HD-Mel and ASCT as a promising salvage regimen for relapsed AML patients for whom autologous peripheral blood stem cells are available.
Medizinische Klinik II, Klinikum der J.W. Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany, g.bug@em.uni-frankfurt.de
Gesine
G
Bug
Johannes
J
Atta
Stefan A
SA
Klein
Bernd
B
Hertenstein
Lothar
L
Bergmann
Simone
S
Boehrer
Sabine
S
Mousset
Dieter
D
Hoelzer
Hans
H
Martin
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000627:therapeutic use*; D008875:Middle Aged; D012008:Recurrence; D016879:Salvage Therapy / Q000379:methods*; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous
D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan