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

Abstract

Summary:Juvenile myelomonocytic leukaemia (JMML) is a rare paediatric disease and allogeneic stem cell transplantation is the only curative approach. The roles of pretransplant treatment, conditioning regimen and graftversus-host disease (GVHD) are still unclear. Eleven children with JMML underwent allogeneic BMT in our institution. Donors were matched unrelated (n = 6) matched siblings (n = 4) and one mismatch family donor. Transplant-related mortality (TRM) was 36%. Three patients relapsed after transplantation. Two of three patients with relapse are in continuous remission after donor lymphocyte infusion or second BMT, respectively. To evaluate the role of pretransplant treatment, conditioning regimen and GVHD, we have summarised our series with other published single centre reports and give an overview on a total of 65 patients with JMML who underwent allogeneic BMT. No significant correlation between pretransplant treatment, conditioning regimen and TRM could be observed. Overall relapse rate is high (47%). TBI is associated with a significantly higher relapse rate (P = 0.012). Other conditioning modalities, intensive chemotherapy and splenectomy prior to stem cell transplantation do not seem to have a significant impact on relapse rate. Patients with or without GVHD showed no significant difference in relapse rate (58% vs 45%). In the event of relapse after transplantation withdrawal of immunosuppression, donor lymphocyte infusion or second transplant was successful in 6/11 patients. Graft-versusleukaemia effect seems to play an essential role in bone marrow transplantation for JMML. Bone Marrow Transplantation (2000) 26, 377-382.

Allogeneic bone marrow transplantation for juvenile myelomonocytic leukemia: a single center experience of 23 patients

“…Intensive chemotherapy given before the start of the conditioning for BMT had a significant adverse effect (P ¼ 0.04 in univariate analysis) in our study on the relapse rate after BMT. This finding is not in agreement with the findings of other authors 11,14,22 and needs further study. The influence of TBI in the conditioning regimen for JMML was studied by Matthes-Martin et al 22 in a single center evaluation of 11 transplants and a review of the literature on single center reports.…”

“…Rapid sustained engraftment in 20 of 22 evaluable children proved that engraftment was not a problem, similar to results in other studies. 14,15,17,22 Factors possibly predicting a relapse, as found by us and by others, relate to karyotype, 14 intensive pre-BMT chemotherapy, conditioning regimen, 11,22 donor type, 11 TCD and GvHD. 15 Manabe et al 14 found in a multivariate analysis on the outcome of 27 JMML patients an abnormal karyotype to be the only significant risk factor for decreased OS.…”

“…In recently published series, 15,22 infectious complications also accounted for the largest number of transplant-related deaths. In the future, it may be possible to reduce the frequency of this complication by pre-emptive antiviral therapy following RT-PCR surveillance of viral nucleic acids in blood samples post-BMT.…”

Successful treatment of JMML relapsed after unrelated allogeneic transplant with cytoreduction followed by DLI and interferon-alpha: evidence for a graft-versus-leukemia effect in non-monosomy-7 JMML

“…2 In spite of the well-documented efficacy of post transplant immunomodulation in other disorders, published work suggesting a graft-versus-leukemia (GVL) effect of post-transplant donor lymphocyte infusion (DLI) or intereferon in JMML is limited, and responding patients have all had monosomy-7 JMML. [4][5][6] We describe a patient who relapsed early after unrelated allogeneic bone marrow transplantation for non-monosomy-7 JMML in whom DLI induced a partial response, and the addition of interferon-alpha (IFN) likely contributed to attaining and sustaining a prolonged complete remission. This observation suggests a role for post-transplant immunotherapy approaches in non-monosomy-7 JMML.…”

“…4,5 Mathes-Martin et al described two JMML patients relapsed after BMT treated with DLI: one patient failed to respond to a dose of 1 Â 10 7 CD 3 þ cells/kg and a second patient with monosomy-7 JMML remained in remission 9 months after receiving chemotherapy followed by three DLI doses (0.5 Â 10 6 Â 2, 1.0 Â 10 6 Â 1 CD3 þ cells/kg). Worth et al described another patient with monosomy-7 JMML relapsed after BMT who received DLI at a dose of 1 Â 10 8 CD3 þ cells/kg.…”