Therapy-related myelodysplastic syndrome in children with medulloblastoma following MOPP chemotherapy

Abstract

Between 1978 and 1988, 20 children with medulloblastoma (MB) of the brain were treated postoperatively with MOPP (nitrogen mustard, vincristine, prednisone, and procarbazine). All but one received post-operative radiation prior to MOPP. Eight of 20 patients remained in continuous complete remission from MB, two of whom eventually developed myelodysplastic syndrome (MDS). Following resection of MB at age 12 months, one patient was treated with 24 courses of MOPP over 2 years without radiation therapy. She developed pancytopenia, and MDS was diagnosed 19 months after the completion of MOPP. Analysis of unstimulated bone marrow (BM) chromosomes showed structural abnormalities involving chromosomes 7, 10, 17, and 21. Eight months later, MDS evolved into acute myeloid leukemia. The second patient was diagnosed with MB at age 7 years and received postoperative craniospinal radiation followed by 12 courses of MOPP over one year. Five months after completion of MOPP, she developed MDS with monosomy 7 on chromosome analysis of bone marrow cells. Therapy-related MDS may be a complication of MOPP chemotherapy for MB in young children.

Myelodysplastic Syndrome Following Therapy for Brain Tumor. Two Case Reports.

“…4,26,27) Since the establishment of the FAB classification for MDS in 1982, only 11 patients with MDS after therapy for malignant brain tumor including our patients have been reported (Table 2). 1,9,11,13,[22][23][24] However, a number of neuro-oncology studies have Cited from references 2 and 3. documented cases of therapy-related AML. The patients presented with aplastic anemia, persistent anemia, prolonged thrombocytopenia, or refractory anemia.…”

Pediatric Therapy-related Myelodysplastic Syndrome/Acute Myeloid Leukemia

“…Cases of t-MDS/AML have occurred in children and adolescents diagnosed with Hodgkin lymphoma (HL), non-Hodgkin lymphoma, Ewing sarcoma, osteosarcoma, medulloblastoma, and acute lymphoblastic leukemia (ALL). [1][2][3][4] Current studies indicate that 1 in 900 adults younger than 45 years of age is a pediatric cancer survivor. 5 Continued improvement in therapies is expected to increase the number of survivors at risk for late sequelae.…”

Treatment-related myelodysplasia in patients with primary brain tumors

“…It appears that patients with primary brain tumors treated with nitrosoureas develop t-MDS/AML at a shorter latency period than do those with other cancers, suggesting a synergistic effect with radiation therapy or a unique property of these alkylating agents. 3,26,28 Latency appears to be even shorter in children. 28 However, this may also simply reflect a selection bias (patients with normal latency die from the brain tumor prior to clinical manifestation of MDS).…”