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

Abstract

Juvenile myelomonocytic leukaemia (JMML) is a clonal myeloproliferative disorder afflicting young children Hasle et al, 2003). Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative strategy and recent large studies indicate an event-free survival of approximately 50% following HSCT (Manabe et al, 2002;Locatelli et al, 2005). Despite the improvement in survival rate, relapse remains the most common cause of treatment failure, affecting one-third of patients (Manabe et al, 2002;Locatelli et al, 2005). Relapse occurs early, at a median of 2-6 months

Feasibility study of preemptive withdrawal of immunosuppression based on chimerism testing in children undergoing myeloablative allogeneic transplantation for hematologic malignancies

“…First, our definition of increasing chimerism was based on the finding that a change between two longitudinal specimens that exceeded assay sensitivity, rather than the percentage increase in autologous signal, as published previously. [2][3][4][5][7][8][9] Second, the frequency of testing in our study was every 14 days in patients with MC, rather than weekly as in other reports. 2,7-9 Third, our samples might have contained a higher proportion of lymphocytes, as all of our patients received T-cell replete transplants, and 65% of our patients received peripheral blood stem cells.…”

“…2,[7][8][9] Use of DLI resulted in the long-term response in 5/20 children with ALL, 9/11 children with myelodysplastic syndrome, 1/6 children with juvenile myelomonocytic leukemia and 2/9 children with AML. 2,[8][9][10] Data in adults with AML showed that all 32 patients with increasing chimerism relapsed despite receiving immunomodulating therapy; 15 however, 4/8 patients with ALL who received DLI for MC showed long-term remission. 19 In 2000, Zetterquist et al 13 evaluated lineage-specific (CD19 þ ) chimerism in children with B-cell ALL.…”

“…Ninety percent of 2,[7][8][9] In patients with increasing chimerism, fast withdrawal of immunosuppression resulted in long-term response in 9/14 children with ALL, 3/7 children with AML, 0/11 children with myelodysplastic syndrome and 0/2 patients with juvenile myelomonocytic leukemia. 2,[7][8][9] Use of DLI resulted in the long-term response in 5/20 children with ALL, 9/11 children with myelodysplastic syndrome, 1/6 children with juvenile myelomonocytic leukemia and 2/9 children with AML. 2,[8][9][10] Data in adults with AML showed that all 32 patients with increasing chimerism relapsed despite receiving immunomodulating therapy; 15 however, 4/8 patients with ALL who received DLI for MC showed long-term remission.…”

“…Since then, a number of European studies have described the use of whole blood (WB) chimerism testing as the basis for initiating immunologic intervention. [2][3][4][7][8][9] Several studies examining lineagespecific chimerism have been published as well, suggesting that the presence of an autologous signal in leukemiaspecific lineage chimerism testing may be a sensitive indicator of minimal residual disease. [10][11][12][13][14] Although most studies agree that the presence of MC following myeloablative transplantation for hematologic malignancies is related to an increased risk of relapse, not all authors could reliably identify 'increasing chimerism', 10 and not all authors agree that the preemptive immunotherapy based on chimerism testing improves clinical outcome.…”

HLA-identical umbilical cord blood transplantation from a sibling donor in juvenile myelomonocytic leukemia

“…Mixed donor-chimerism after SCT in JMML has been shown to be an important predictor for relapse, therefore discontinuation of immunosuppressive therapy (IST) is the first step to prevent relapse if this occurs early after transplantation. 11 To avoid relapse, a second stem cell transplantation was considered, but the parents were very reluctant to proceed, because of the absence of any clinical signs of JMML and the excellent clinical condition of the child. Therefore, 6-mercaptopurine (6-MP) (average dose 40 mg/m 2 ) was started on day 145 after SCT.…”