Acute myeloblastic leukemia in a patient with non-Hodgkin's lymphoma early after double peripheral blood stem-cell transplantation.

Abstract

Double peripheral blood stem-cell transplantation (PB-SCT) has been reported to be a more effective protocol than single PBSCT for chemotherapy-resistant and poor-prognosis non-Hodgkin's lymphoma (NHL) (1). In this letter, we present a rare case of secondary acute myeloblastic leukemia (AML) that occurred early after double PBSCT for NHL. A 20-year-old woman visited our hospital with a bulky mass in the upper abdomen in August 1998. Because pathologic examination revealed NHL (diffuse large B-cell type) in clinical stage IV, combination chemotherapy was started. Although the patient received several courses of chemotherapy, she did not achieve complete remission (CR). Double autologous PBSCT was therefore performed using PBSC collected after treatment with a high dose of etoposide and granulocyte colony-stimulating factor. There was no evidence of bone-marrow involvement or myelodysplastic alterations before PBSCT. The first PBSCT was performed using ranimustine (MCNU), carboplatin (CBCDA), etoposide (VP-16), and cyclophosphamide (MCVC regimen) (2), 6 months after the start of conventional chemotherapy. Three months after the first PBSCT, the patient underwent a second PBSCT using a modified MCVC-conditioning regimen with infusion of PBSC, which had been cryopreserved on the day on which the first PBSC collection had been performed. One month after the second PBSCT, the patient was evaluated as having achieved CR. Three months after the second PBSCT, the patient was diagnosed as having secondary AML (M0). Chromosomal analysis of myeloblasts showed add (22)(q13) (46, XX, add (22)(q13) [6]/46, idem, add(2)(q23) [12]/46, idem, t(1;3)(p36;p21)[2]), which has been reported to be seen in patients with secondary leukemia after stem-cell transplantation (3). Neither T-cell receptor Cβ1 nor immunoglobulin heavy-chain rearrangement was detected in myeloblasts by Southern blot analysis. The patient died of respiratory failure with pneumonia 6 months after the onset of secondary leukemia without any evidence of NHL relapse. Secondary myelodysplastic syndrome (MDS) and AML occurring early after stem-cell transplantation (SCT) such as that in our case is very rare. The median times from transplantation to onset of secondary malignancies have been reported to be 31 to 44 months, although it was stated in one report that 4% of cases occurred within the first 4 months (3, 4). The onset of secondary AML after tandem PBSCT in this case may be related to more profound immunosuppression than that in single PBSCT. Since high-dose topoisomerase II inhibitors have been reported to be the drugs most likely to cause secondary malignancies, accumulation of high-dose etoposide administered before PBSCT (total 4,540 mg) and even before the harvest of PBSC (total 2,440 mg) might be related to the early onset of secondary AML in this case (5). Add(22)(q13) observed in this patient has been reported to be seen in patients with secondary MDS following autologous SCT for lymphoid malignancies. Secondary leukemia is usually chemotherapy resistant and has a poor prognosis. Therefore, investigation of risk factors for secondary malignancies and evaluation of high-risk patients are important for follow-up of patients who have undergone autologous PBSCT. Larger-scale studies are needed to obtain evidence of an increased risk of the occurrence of secondary MDS/AML following tandem PBSCT compared with the risk following single PBSCT. Satoshi Hashino Nobuyasu Toyoshima Koji Chiba Sachiko Suzuki Mitsutoshi Kurosawa Manabu Musashi Masahiro Asaka Department of Gastroenterology and Hematology Hokkaido University Graduate School of Medicine Sapporo, Japan