Role of allogeneic bone marrow transplantation from an HLA‐identical sibling or a matched unrelated donor in the treatment of children with juvenile chronic myeloid leukaemia

Abstract

Seven children (age range 1.8-11 years) with juvenile chronic myelomonocytic leukaemia (JCML) received an allogeneic bone marrow transplantation (BMT), four from an HLA-identical sibling and three from a matched unrelated donor. In the four children transplanted using an HLA-identical sibling, conditioning regimen included busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM), whereas graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine-A (Cs-A). The preparative regimen was well tolerated and all patients engrafted promptly. None of the patients have relapsed and all four children remain in haematological remission after an observation time of 7, 24, 25 and 48 months, respectively. Of the three children given BMT from an unrelated volunteer, one was < 2 years of age and she received the BU/CY/L-PAM regimen. In view of the increased risk of graft rejection described in patients transplanted from unrelated donors, we chose to prepare the other two patients with fractionated total body irradiation (TBI), thiotepa and CY. Cs-A, short-term methotrexate and Campath-1G in vivo were employed to prevent GVHD in this group of patients. Graft failure with autologous reconstitution of haemopoiesis occurred in the child given the chemotherapy-based regimen. One of the two girls given TBI relapsed after BMT; therefore only one of the three patients who received a marrow transplant from a matched unrelated donor survives in complete haematological remission 10 months after BMT. Our study suggests that the conditioning regimen we employed for allogeneic BMT from a compatible sibling is an effective means of eradicating the leukaemic clone. In our experience, results obtained using unrelated donors are less satisfactory and, at present, the use of such donors seems to be riskier and associated with a lower success rate as compared with BMT from an HLA-identical sibling.

Allogeneic hematopoietic stem cell transplantation for 27 children with juvenile myelomonocytic leukemia diagnosed based on the criteria of the International JMML Working Group

“…[5][6][7][8][9][10][11] However, the results concerning prognostic factors after SCT were not necessarily clear partly because of inaccuracy of the diagnosis. It was not until recently that the disease entity of JMML was established.…”

“…Niemeyer et al 4 reported that the probability of survival at 10 years was 39% for patients who received bone marrow transplantation (BMT) and 6% for patients who did not receive it. Allogeneic BMT was frequently employed in this disease, [5][6][7][8][9][10][11] but interpretation of the results was difficult due to variability in conditioning regimens, type of donors, and pretransplant therapy. In addition, it was also complicated by the inaccur- acy of the diagnosis in the past: patients of other myelodysplastic disorders seemed to be included in JMML.…”

Substitution of cyclophosphamide and busulfan by fludarabine, treosulfan and melphalan in a preparative regimen for children and adolescents with Shwachman–Diamond syndrome

“…The choice of tailoring a preparative regimen for SDS patients by adding a second alkylating agent was based on the results of a preliminary study demonstrating the safety of combining melphalan with busulfan 30 and on the fact that the retrospective analysis of the EWOG-MDS group showed that a myeloablative preparative regimen including a second alkylator was associated with a better event-free survival (EFS) and a lower relapse rate in comparison with regimens including TBI. 31 Similarly, poorer results of HSCT for SDS-associated myelodysplasia/acute leukemia have been reported.…”

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

“…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.…”

“…The BU, CY and melphalan (Mel) regimen, used from December 1996 onwards, was proposed by Locatelli et al 17 Three patients received the CY/TBI-based regimen in this period because of pre-existent hepatic dysfunction. TBI was given as a single fraction of 7-7.5 Gy to patients younger than 10 years, and in two fractions of 6 Gy each on two consecutive days to children aged X10 years.…”