Extramedullary Relapse Despite Graft-Versus-Leukemia Effect after Bone Marrow Transplantation in a Girl with Juvenile Myelornonocytic Leukemia

Abstract

A 12 year-old girl with juvenile myelomonocytic leukemia (JMML) and monosomy 7 underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched brother. To monitor the engraftment and the course of the disease we used fluorescence in situ hybridization (FISH) with probes specific for the centromeres of chromosomes X, Y and 7. Complete hematological remission was achieved and confirmed by the virtually exclusive presence of normal male cells in the bone marrow (BM). Acute graft-versus host disease (GvHD) was treated with prednisone and cyclosporine A (CSA) and female cells with monosomy 7 reoccurred in the peripheral blood (PB) and BM. After discontinuation of the immunosuppressive therapy, the leukemic cells with monosomy 7 disappeared again from these compartments. One year after transplantation, isolated extramedullary relapses occurred in lymph nodes and skin, followed by dissemination of blast cells into the BM, whereas the PB cells remained of donor origin. The fact that the leukemic cells fluctuated with the intensity of the immunosuppressive treatment provides evidence of a graft versus leukemia (GvL) effect in this unusually old girl with JMML with a unique extramedullary disease progression.

Chimaerism analyses and subsequent immunological intervention after stem cell transplantation in patients with juvenile myelomonocytic leukaemia

“…If cessation of IST had not been effective, DLI or a second HSCT was considered as the second line therapy. In our series, discontinuation of IST was unsuccessful once haematological relapse had been diagnosed, although other investigators reported three JMML patients with haematological or cytogenetic relapse who were successfully treated by cessation of IST alone (Lutz et al , 1996; Orchard et al , 1998; Kressler et al , 1999). We suggest that immediate withdrawal of IST is indicated after the first detection of MC for two reasons.…”

“…Several studies showed that chronic graft‐ versus ‐host disease (GVHD) was associated with a lower risk of relapse and improved survival (Manabe et al , 2002; Smith et al , 2002). Withdrawal of immunosuppressive drugs can control leukaemia in some patients (Rassam et al , 1993; Lutz et al , 1996; MacMillan et al , 1998; Orchard et al , 1998; Kressler et al , 1999; Ohta et al , 2000). There have been a few reports on patients successfully treated by donor leucocyte infusion (DLI) (Matthes‐Martin et al , 2000; Worth et al , 2003; Neudorf et al , 2004; Pulsipher et al , 2004).…”

Allogeneic bone marrow transplantation for juvenile myelomonocytic leukaemia: a single centre experience and review of the literature

“…This patient has been recently reported elsewhere. 12 Despite GVHD prophylaxis with cyclosporine and MTX she developed acute GVHD grade III and chronic GVHD, which were treated with prednisolone and cyclosporine. On day +200 she relapsed and 30% female cells with monosomy 7 could be detected in the bone marrow.…”

Donor leukocyte infusion after hematopoietic stem cell transplantation in patients with juvenile myelomonocytic leukemia

“…Withdrawal of immunosuppressive drugs is usually the first measure, which by itself can control leukemia in a limited number of patients. Several reports [25][26][27][28][29][30] and the clinical course of patient CZ019 in this series indicate the efficacy of withdrawal of immunosuppressive therapy in some patients with relapsed JMML, suggesting a GVL effect in JMML. In the case of nonresponse and for patients suffering disease recurrence after discontinuation of immunosuppressive agents, DLI or second HSCT may be considered.…”