Low risk of secondary leukemias after chemotherapy without mechlorethamine in childhood Hodgkin's disease. German-Austrian Pediatric Hodgkin's Disease Group.
BACKGROUND
In the last two decades, it has become evident that secondary leukemias after Hodgkin's disease (HD) are mainly caused by the treatment with alkylating agents, especially mechlorethamine. Since 1978, the German-Austrian trials for childhood HD have used combined chemoradiotherapy without mechlorethamine.


METHODS
The risk of secondary hematologic malignancies (SHM) was assessed in the total cohort of 667 children treated in four consecutive German-Austrian trials between 1978 and 1990. Primary chemotherapy for stages IA/B and IIA consisted of two cycles of vincristine, procarbazine, prednisone, and doxorubicin (OPPA) or OPA (without procarbazine) and, for more advanced stages, of two cycles of OPPA or OPA plus two, four, or six cycles of COPP or COMP (C, cyclophosphamide; M, methotrexate). Radiotherapy was given in the first study to extended fields, and in later trials to involved fields only. In 591 patients, only primary therapy was given; 76 patients (11%) needed additional salvage therapy. The actuarial survival rate at 15 years is 94%.


RESULTS
SHM developed in 5 of 667 patients: four acute myeloid leukemias (AMLs) and one myelodysplastic syndrome (MDS). The estimated cumulative risk for SHM at 15 years is 1.1% (95% CI, 0.0% to 2.2%). Salvage therapy was a significant risk factor for SHM (relative risk, 7.25; P = .03), whereas age, sex, stage of HD, splenectomy, and amount of alkylating agents were not.


CONCLUSIONS
The observed risk of SHM is smaller than in other studies (adults and children) in which chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) was given. This difference can be attributed to the lower cumulative doses of alkylating agents, the absence of mechlorethamine in the chemotherapy, and the small number of patients who needed salvage therapy in the presented cohort. In general, differences in the incidence of SHM after HD reflect complex differences between treatment strategies.
Schellong
G
G
Department of Pediatric Hematology and Oncology, University Children's Hospital, Münster, Germany.
Riepenhausen
M
M
Creutzig
U
U
Ritter
J
J
Harbott
J
J
Mann
G
G
Gadner
H
H
D000293:Adolescent; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000139:chemically induced*; D008297:Male; D008466:Mechlorethamine / Q000009:adverse effects*; D016609:Neoplasms, Second Primary / Q000139:chemically induced; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011344:Procarbazine / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D016879:Salvage Therapy; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D018906:Antineoplastic Agents, Alkylating; D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone