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Treatment of Relapsed or Refractory Childhood MLDS
Source: Childhood Myeloid Proliferations Associated With Down Syndrome Treatment (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: September 16, 2024 · Captured 2026-09-09.
Selected source text with whitespace normalised. This Triangle page is not an NCI PDQ summary.
A small number of trials address outcomes in children with MLDS who relapse after initial therapy or who have refractory MLDS. In three prospective trials of children with newly diagnosed MLDS, outcomes were poor for those who relapsed (4 of 11, 2 of 9, and 2 of 12 patients who relapsed survived).[9,13,16] Thus, these children are treated similarly to children without Down syndrome, with an intensive reinduction chemotherapy regimen. If a remission is achieved, therapy is followed by an allogeneic hematopoietic stem cell transplant (HSCT).
Treatment options for children with refractory or relapsed MLDS include the following:
Chemotherapy, which may be followed by an allogeneic HSCT.
Evidence (treatment of children with refractory or relapsed MLDS):
Four analyses have specifically examined children with relapsed or refractory MLDS.[22-25]
The Japanese Pediatric Leukemia/Lymphoma Study Group reported the outcomes of 29 patients with relapsed (n = 26) or refractory (n = 3) MLDS. As expected with Down syndrome, the children in this cohort were very young (median age, 2 years); relapses were almost all early (median, 8.6 months; 80% <12 months from diagnosis); and 89% had M7 French-American-British classification.[22][Level of evidence C1]
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The Japanese Pediatric Leukemia/Lymphoma Study Group reported the outcomes of 29 patients with relapsed (n = 26) or refractory (n = 3) MLDS. As expected with Down syndrome, the children in this cohort were very young (median age, 2 years); relapses were almost all early (median, 8.6 months; 80% <12 months from diagnosis); and 89% had M7 French-American-British classification.[22][Level of evidence C1]
In contrast to the excellent outcomes achieved after initial therapy, only 50% of the children attained a second remission, and the 3-year OS rate was 26%. Attainment of second remission was more successful the later the relapse occurred after completing initial therapies.
The Japanese Pediatric Leukemia/Lymphoma Study Group reported the outcomes of 29 patients with relapsed (n = 26) or refractory (n = 3) MLDS. As expected with Down syndrome, the children in this cohort were very young (median age, 2 years); relapses were almost all early (median, 8.6 months; 80% <12 months from diagnosis); and 89% had M7 French-American-British classification.[22][Level of evidence C1]
Approximately one-half of the children underwent allogeneic transplant, and no advantage was noted for transplant compared with chemotherapy. However, the number of patients was small.
A Center for International Blood and Marrow Transplant Research study of children with MLDS who underwent allogeneic HSCT reported the following results:[23][Level of evidence C1]
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A Center for International Blood and Marrow Transplant Research study of children with MLDS who underwent allogeneic HSCT reported the following results:[23][Level of evidence C1]
A similarly poor outcome, with a 3-year OS rate of 19%.
A Center for International Blood and Marrow Transplant Research study of children with MLDS who underwent allogeneic HSCT reported the following results:[23][Level of evidence C1]
The main cause of failure after transplant was relapse, which exceeded 60%. Survival was significantly worse for patients who relapsed early.
A Center for International Blood and Marrow Transplant Research study of children with MLDS who underwent allogeneic HSCT reported the following results:[23][Level of evidence C1]
The transplant-related mortality was approximately 20%.
A Japanese registry study reported better survival after transplant of children with MLDS using reduced-intensity conditioning regimens compared with myeloablative approaches. However, the number of patients was very small (n = 5), and the efficacy of reduced-intensity approaches in children with MLDS requires further study.[24][Level of evidence C2]
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The largest study to date was conducted by a consortium of pediatric cooperative groups and select North American institutions. The study retrospectively evaluated children with MLDS to determine their outcomes and prognostic factors for survival after relapse or refractory disease.[25]
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The largest study to date was conducted by a consortium of pediatric cooperative groups and select North American institutions. The study retrospectively evaluated children with MLDS to determine their outcomes and prognostic factors for survival after relapse or refractory disease.[25]
The most common site of relapse was bone marrow (61 of 62 patients), and no CNS relapses were reported.
The largest study to date was conducted by a consortium of pediatric cooperative groups and select North American institutions. The study retrospectively evaluated children with MLDS to determine their outcomes and prognostic factors for survival after relapse or refractory disease.[25]
Median time to relapse was 6.8 months, and 82% of relapses occurred within 12 months of initial diagnosis.
The largest study to date was conducted by a consortium of pediatric cooperative groups and select North American institutions. The study retrospectively evaluated children with MLDS to determine their outcomes and prognostic factors for survival after relapse or refractory disease.[25]
Time to relapse, use of HSCT, and attainment of second complete remission (CR) before transplant were prognostically significant.
The largest study to date was conducted by a consortium of pediatric cooperative groups and select North American institutions. The study retrospectively evaluated children with MLDS to determine their outcomes and prognostic factors for survival after relapse or refractory disease.[25]
For the entire cohort, the OS rate was 22.1%, the EFS rate was 20.9%, and the cumulative relapse rate was 79.1%.
The largest study to date was conducted by a consortium of pediatric cooperative groups and select North American institutions. The study retrospectively evaluated children with MLDS to determine their outcomes and prognostic factors for survival after relapse or refractory disease.[25]
The median time from relapse or refractory disease to time of death was 5.1 months (0.4–41 months).
The largest study to date was conducted by a consortium of pediatric cooperative groups and select North American institutions. The study retrospectively evaluated children with MLDS to determine their outcomes and prognostic factors for survival after relapse or refractory disease.[25]
The 3-year OS rate was 46% for those who achieved remission (45% of patients).
The largest study to date was conducted by a consortium of pediatric cooperative groups and select North American institutions. The study retrospectively evaluated children with MLDS to determine their outcomes and prognostic factors for survival after relapse or refractory disease.[25]
HSCT was performed in 29 patients. Undergoing HSCT in second CR was critically important, with 6 of 19 patients relapsing after HSCT if initially in second CR, compared with 9 of 10 patients relapsing if they went to transplant when not in second CR. Among the 29 HSCT recipients, the 3-year OS rate was 39.8%, and the EFS rate was 36.7%.
The largest study to date was conducted by a consortium of pediatric cooperative groups and select North American institutions. The study retrospectively evaluated children with MLDS to determine their outcomes and prognostic factors for survival after relapse or refractory disease.[25]
Only 3 of 33 patients who received chemotherapy alone ultimately survived (3-year OS and EFS rates, 6.4%).
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