Ronald L. Chard

A Comparison of Marrow Transplantation with Chemotherapy for Children with Acute Lymphoblastic Leukemia in Second or Subsequent Remission

The progress of 24 children with acute lymphoblastic leukemia treated with cyclophosphamide, total-body irradiation, and marrow transplantation during a second or subsequent remission was compared with that of 21 children treated with conventional chemotherapy after they had entered a second remission. Eleven of the transplantation group are alive, including nine in continuing complete remission for 17 to 55 months; only two of the chemotherapy group are alive, one in complete remission after 20 months. Relapse was the major cause of failure in both groups. Acute and chronic graft-versus-host disease in the transplantation group and leukoencephalopathy in both groups were the other major causes of morbidity and mortality. This study demonstrates that marrow transplantation currently offers the best chance of long-term remission and potential cure after a child with acute lymphoblastic leukemia has had a relapse in the marrow.

Lymphomatous presentation of childhood acute lymphoblastic leukemia a subgroup at high risk of early treatment failure

Multivariate analyses of the clinical course of 1537 children with acute lymphoblastic leukemia (ALL) identified a subgroup which experienced short remission duration and a high incidence of extramedullary relapse. The patients differed from other ALL patients by the presence at diagnosis of two or more of a constellation of clinical and laboratory features: organomegaly or mass disease, Erosette positivity, hemoglobin level greater than 10 g/dl, leukocyte count greater than 50,000/μl, male predominance, and older age. This type of presentation of ALL is referred to as the “lymphoma syndrome” (LS) since such patients exhibit a pattern of several clinical and laboratory features which were observed repeatedly but in differing combinations, and some of which clinically resemble lymphoma. A subsequent database from 2231 patients was analyzed. Patients with a mediastinal mass, massive splenomegaly, or massive adenopathy, alone or in combination, had a worse outcome when the patient also had either leukocytosis, E‐rosette‐positive lymphoblasts, or a normal or near normal hemoglobin (Hb) level at diagnosis. Similarly, the above three laboratory features alone or in combination did not predict less than 40% disease‐free survival (DFS) unless they were accompanied by at least one of the clinical features of mass disease. When at least one clinical feature and at least one laboratory feature were present, the overall DFS was 36% 6 years after diagnosis versus 64% for all other patients. The association of these features with poor prognosis remained significant after adjusting for the level of leukocyte count at diagnosis, age at diagnosis, and sex of the patients. Patients with this recurrent syndrome of features do not represent a homogeneous biologic entity but they constitute a subgroup of patients with ALL having a high risk of treatment failure using current therapies, including failure to achieve remission, early relapse, and increased frequency of relapse in extramedullary sites. They deserve early recognition at diagnosis and selection of treatment strategies appropriate for very high risk ALL.

Seizures associated with vincristine sulfate therapy

Generalized seizures occurring five to six days following an intravenous injection of vincristine are described in four patients. No other cause for the seizures was documented. They occurred following doses within the normal therapeutic range (1.5 to 2 mg. per square meter once weekly) and in the absence of hyponatremia, which has previously been implicated in the pathogenesis of vincristine-induced seizures.

Thrombotic thrombocytopenic purpura

Three patients, 6, 14, and 15 years old, survived an acute illness that closely resembled thrombotic thrombocytopenic purpura. The children were closely monitored with coagulation studies and, in addition, kinetic measurements of platelets and fibrinogen were performed. These studies provided no evidence that either heparin or aspirin and dipyridamole influenced the course of the disease. The possible benefit of corticosteroid therapy could not be evaluated. Significant increases in titers to Coxsackie B viruses developed in two of the patients.

4'-DEMETHYL-EPIPODOPHYLLOTOXIN-|[beta]|-THENYLIDENE GLUCOSIDE |[lpar]|VM-26|[rpar]||[lpar]|NSC-122819|[rpar]|: A NEW DRUG FOR NEUROBLASTOMA

Neuroblastoma remains a great challenge in pediatric oncology. The demonstration of an effective new drug for neuroblastoma would be a worthwhile addition to the present surgical, radiation and chemotherapeutic modalities.VM-26 is a lipophilic podophyllotoxin with demonstrated activity in human tumors. CCSG studied its effect in 14 children with advanced stage IV neuroblastoma resistant to 3-6 chemotherapeutic agents. VM-26 was given as a 1 hour intravenous infusion on a weekly schedule of 130 mg/m2 × 3, 150 mg/m2 × 3, then 180 mg/m2 until progression of disease. Of 12 evaluable patients, one had a complete response of 211 days duration, four had partial responses of 21+, 21+, 58 and 78 days duration, four had either static disease or transient subjective responses, and three had no response. Dose-limiting toxicity was hematologic, with severe leukopenia occurring in five patients and thrombocytopenia in four patients. The toxicity was temporary in that most patients were able to tolerate the scheduled dosage escalations.A response rate of 42% is taken as evidence for further trials of this drug in neuroblastoma.