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An unusual case of B-ALL occurring in a patient with acute promyelocytic leukemia in remission after two hematopoietic SCTs: whose are the leukemic cells?

Bone Marrow Transplantation volume 49, pages 1237–1238 (2014)Cite this article

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We read with interest the recent article by Shiozaki et al.,1 reporting a case of donor cell leukemia (DCL) occurring in a patient who previously underwent cord blood (CB) transplantation for myelodysplastic syndrome and describing the clinical and biological differences between DCL arising after hematopoietic SCT (HSCT) from either CB or BM sources. We would like to comment on these issues, reporting an unusual case of DCL in a patient with a long history of acute promyelocytic leukemia (APL).

A 45-year-old man presented in December 2004 with intermediate-risk APL, positive for t(15;17), resulting in the PML-RARA chimeric transcript. He achieved hematologic CR with a remission induction cycle including all-trans retinoic acid (ATRA) and idarubicin. He subsequently underwent three consolidation chemotherapy cycles. Molecular CR was obtained at the end of the consolidation treatment in May 2005. Two months later, the patient exhibited molecular relapse, so that he underwent salvage chemotherapy with ATRA, cytarabine and mitoxantrone, reaching a second molecular CR. The patient was subsequently treated with an allogeneic peripheral blood (PB) HSCT from his HLA-identical male sibling (donor 1), with myeloablative conditioning (BU 12.8 mg/kg in 4 days and CY 120 mg/kg in 2 days). Short-term MTX and CyA therapy was used as GVHD prophylaxis. Full donor 1 chimerism was obtained by day +59, as assessed by PCR-based analysis of autosomal short tandem repeats (microsatellites) on DNA samples extracted from BM cells. Unfortunately, in February 2008, the patient experienced another molecular recurrence, initially treated with DLIs and, then, with arsenic trioxide, resulting in molecular CR for the third time. Then, he underwent a second allogeneic transplantation from another HLA-identical 52-year-old male sibling (donor 2), using BM as the stem cell source. On this occasion, the conditioning regimen consisted of TBI (800 cGy), fludarabine 120 mg/m2 in 4 days, CY 80 mg/kg in 2 days and ATG 40 mg/kg/day for 2 days. Short-term MTX and CyA were administered as GVHD prophylaxis. The patient became a full chimera of donor 2 on day +30, did not experience significant post-transplant complications and had a 5-year disease-free interval. In July 2013, fever, asthenia, weight loss and multiple superficial adenopathies occurred. The complete blood count (CBC) showed pancytopenia (WBC 1.0 × 109/L, Hb 10 g/dL, Plt 11 × 109/L) in the absence of coagulopathy. The differential count documented 22% neutrophil, 69% lymphocytes, 5% myelocytes, 1% metamyelocytes and 3% agranular blasts. Either morphologic APL relapse or the occurrence of therapy-related myeloid neoplasm was initially suspected. Surprisingly, BM aspirate and trephine biopsy examinations demonstrated >90% B-lymphoid blasts. A complex karyotype was observed on cytogenetic analysis. The presence of either PML-RARA or BCR-ABL fusion transcripts was excluded. Unexpectedly, the microsatellite analysis showed full chimera donor 2, thus diagnosing B-ALL of donor origin. The patient was treated with combination chemotherapy (VCR, idarubicin, CY and dexamethasone), but failed to achieve remission. In detail, BM aplasia was initially documented, with a subsequent rapid increase of BM blast count (70%). Therefore, he has been enrolled in phase II protocol based on the use of blinatumomab, an antibody BiTE anti-CD19. At the time of publication, he is in hematologic CR, with a normal CBC, after two cycles.

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Authors and Affiliations

  1. Department of Medical and Surgical Sciences, Section of Hematology, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy

    S Bigliardi, M Morselli, L Potenza, P Bresciani, A Cuoghi, V Coluccio, G Riva, A Paolini, V Fantuzzi, L Faglioni, V Nasillo, A Messerotti, R Marasca, F Narni, M Luppi & F Forghieri

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  1. S Bigliardi
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Correspondence to M Luppi.

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Bigliardi, S., Morselli, M., Potenza, L. et al. An unusual case of B-ALL occurring in a patient with acute promyelocytic leukemia in remission after two hematopoietic SCTs: whose are the leukemic cells?. Bone Marrow Transplant 49, 1237–1238 (2014). https://doi.org/10.1038/bmt.2014.119

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