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Conditioning with fludarabine alone and allogeneic transplantation as a successful rescue therapy for persistent, severe iatrogenic aplasia after relapse of acute myeloid leukemia

Bone Marrow Transplantation volume 39, pages 53–54 (2007)Cite this article

Persistent iatrogenic bone marrow aplasia after salvage therapy for acute myeloblastic leukemia (AML) is a difficult clinical problem. The policy of close observation and supportive therapy with hematopoietic growth factors while waiting for spontaneous bone marrow recovery has not proved successful. In this setting, non-myeloablative allogeneic stem cell transplantation (NST) may be the only chance for short-term and long-term survival. The appropriate doses, schedule and intensity of the conditioning regimen are still unresolved issues. We report a patient with relapsed AML who was successfully treated with NST using only fludarabine as a chemotherapeutic agent in the conditioning regimen.

In March 2005, a 51-year-old woman presented with pancytopenia. A bone marrow aspirate showed 77% types I and II blast cells positive for CD117, CD33 and CD13. There were no Auer rods. The karyotype was 46,XX, del(3)(p13) in 20/20 metaphases. A diagnosis of AML type M2, according to the French–American–British classification was made, belonging to the intermediate risk group according to Medical Research Council criteria. In May 2003, the patient had been treated for bilateral ductal-mammary carcinoma in situ and underwent bilateral mastectomy followed by adjuvant chemotherapy consisting of six cycles of chemotherapy (cyclophosphamide, epirubicin and 5-fluorouracil) and tamoxifen. Genetic testing revealed germline BRCA-1 and BRCA-2 genes, but because of familial occurrence of breast cancer, prophylactic oophorectomy was performed. The patient was treated for leukemia at another institution with induction chemotherapy (daunorubicin and cytosine arabinoside) obtaining complete hematological remission. Afterwards, she received two consolidation cycles, the last one including high-dose cytosine arabinoside. The option of allogeneic stem cell transplantation was discussed with the patient because of the possibility that the leukemia could be secondary to previous chemotherapy, but the deletion of chromosome 3p was judged as nonspecific for secondary leukemia and it was decided that a search for a donor and transplantation be postponed until an eventual leukemia relapse. The patient suffered from relapse in January 2006, with morphological and immuno-phenotypic characteristics of AML identical to those observed previously. Re-induction treatment was administered with amsacrine and cytosine arabinoside and the patient was transferred to our hospital. According to Swedish National Guidelines for AML, a bone marrow aspiration was performed on day +15 after start of chemotherapy. The bone marrow was hypocellular with 30% myeloblasts. Because of the resistant nature of the leukemia, therapy with fludarabine, high-dose cytosine arabinoside and idarubicin was commenced in spite of hypoplasia. Bone marrow aspirations on day 15 and day 28 showed no cells, which could be examined. A bone marrow biopsy showed hypocellularity with a few bone marrow cells, which were difficult to characterize. Flow cytometry did not reveal any sign of AML. The morphological picture was identical to severe aplastic anemia. At that moment it was impossible to tell with certainty if the AML stem cell clone was present or not. An unrelated HLA-identical donor was found, and the patient underwent NST after 2 months of continuing aplasia with regular platelet transfusions and leukocyte counts 0–0.1 × 109/l. The conditioning regimen consisted of daily intravenous fludarabine 25 mg/m2 from day −3 to day −1, daily antithymocyte globulin (ATG) (Fresenius) 10 mg/kg from day −5 to day −2. Cyclosporine and methotrexate (8 mg/m2, days +2, +4 and +8) were administered for graft-versus-host disease (GVHD) prophylaxis. A total of 6.08 × 106 unmanipulated peripheral CD34+ cells/kg were infused. Neutrophil and platelet engraftment occurred day +24 and day +28. The course of recovery was complicated by bacterial infection of the breast prostheses, which were surgically removed. The infection subsided rapidly. Bone marrow aspiration was normocellular on day +40 and showed complete hematological remission. Chimerism analysis showed 16% donor cells on day +30, and on day 50 they represented only 6% of the cells. The patient was discharged day +42 after transplantation. The course was uneventful until 3 months after transplantation when relapse occurred. The patient is currently at home 6 months after transplantation and in complete remission again after chemotherapy and donor lymphocyte infusions (DLI). There has been no sign of acute or chronic GVHD.

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  1. Department of Hematology/Medicine, University Hospital of Northern Sweden, Umeå, Sweden

    V Lazarevic & A Wahlin

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  1. V Lazarevic
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Correspondence to V Lazarevic.

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Lazarevic, V., Wahlin, A. Conditioning with fludarabine alone and allogeneic transplantation as a successful rescue therapy for persistent, severe iatrogenic aplasia after relapse of acute myeloid leukemia. Bone Marrow Transplant 39, 53–54 (2007). https://doi.org/10.1038/sj.bmt.1705541

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