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Chimerism analyses by sex-chromosome analysis confused relapse with donor cell leukemia after sex-mismatched allo-SCT

Bone Marrow Transplantation volume 47, pages 1583–1584 (2012)Cite this article

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Donor cell leukemia (DCL) is a rare complication of allogeneic hematopoietic SCT (allo-HSCT). Chimerism analysis is usually used to distinguish DCL from relapse of original leukemia. In cases of sex-mismatched donors, sex-chromosome analysis is widely used to assess the chimeric status. We report a case of Philadelphia (Ph) chromosome-positive ALL (Ph+ALL). Sex-chromosome analyses showed a donor pattern at relapse, leading to a misleading diagnosis of DCL.

A 44-year-old Japanese male developed Ph+ALL and achieved CR after chemotherapy including dasatinib. He then received allogeneic PBSCT from a sex-mismatched and HLA-identical sibling donor, using a conditioning regimen consisting of etoposide, CY and TBI. Prophylaxis for GVHD included CYA plus MTX. The patient developed chronic hepatic GVHD 4 months after PBSCT and was given prednisolone (PSL) and mycophenolate mofetil (MMF). Complete donor-type chimerism was maintained. FISH revealed XX in 100% of BM, whereas G-band karyotyping analysis showed the donor-type chromosome. No leukemic cells were observed in BM 15 months after PBSCT, although minor BCR-ABL mRNA was detected. Based on the recognition of molecular relapse, the patient was started on dasatinib, and PSL and MMF were stopped. T315I BCR-ABL mutation was confirmed after starting dasatinib. The number of leukemic cells gradually increased in peripheral blood and BM. FISH revealed that 99.8% of the leukemic cells were XX, whereas G-band karyotyping showed complexed chromosomes, including XX. DCL was therefore suspected. However, flow-cytometric analysis (FCM) revealed the same pattern as observed at original diagnosis of ALL, and T315I BCR-ABL mutation was demonstrated. These analyses were inconsistent with those of DCL. We could not assess the patient’s G-band karyotyping, which showed complexed karyotypes including chromosome 9, whereas original karyotypes had shown a donor pattern of inv(9)(p12q13). 46,XX,inv(9)(p12q13) is the normal variant observed in 1.65% of the Japanese population.1 Chimerism analysis of purified CD19-positive leukemic cells by variable number of tandem repeat (VNTR) analysis showed 56% of cells with the recipient pattern. Purified CD19-positive cells from BM included approximately 90% leukemic cells. The patient died 17 months after PBSCT. VNTR analysis of purified CD19-positive leukemic cells indicated a 98% recipient pattern in BM at autopsy. Table 1 shows the results of analyses corresponding to the clinical history (Supplementary Figures 1 and 2).

Table 1 Status of each BM analysis
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Authors and Affiliations

  1. Stem Cell Transplantation Center, Hokkaido University Hospital, Sapporo, Japan

    T Matsukawa, A Shigematsu, S Asanuma, A Yasumoto, H Goto, M Takahata, T Endo, J Tanaka, S Hashino & M Imamura

  2. Department of Clinical Laboratory and Transfusion, Hokkaido University Hospital, Sapporo, Japan

    A Shigematsu, K Hayasaka, S Fujisawa & C Shimizu

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  1. T Matsukawa
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Correspondence to T Matsukawa.

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Matsukawa, T., Shigematsu, A., Hayasaka, K. et al. Chimerism analyses by sex-chromosome analysis confused relapse with donor cell leukemia after sex-mismatched allo-SCT. Bone Marrow Transplant 47, 1583–1584 (2012). https://doi.org/10.1038/bmt.2012.61

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