Background Modern intensive chemotherapy regimens have improved the prognosis for patients with adult acute lymphocytic leukemia (ALL). With these regimens, the complete response rates are now reported to be > 80%, and the long-term survival rates range from 30% to 45%. The current analysis updated the long-term results with the original hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) program, with a median follow-up time of 63 months. Methods Between 1992 and 2000, 288 patients were treated with Hyper-CVAD. The median age of the patients was 40 years, and 59 patients (20%) were > or = age 60 years. The incidence of Philadelphia chromosome (Ph)-positive ALL was 17%, and the incidence of of T-cell ALL was 13%. Results A complete response (CR) was achieved in 92% of patients. The induction mortality rate was 5% (2% if the patient's age was or = 60 years). With a median follow-up time of 63 months, the 5-year survival rate was 38% and the 5-year CR duration rate was 38%. Multivariate analysis of prognostic factors for CR duration identified the following adverse factors: age > or = 45 years, leukocytosis > or = 50 x 10(9)/L, poor performance status (an Eastern Cooperative Oncology Group score of 3-4), Ph-positive disease, French-American-British L2 morphology, > 1 course to achieve CR, and Day 14 bone marrow blasts > 5%. Patients were divided into low-risk (risk score 0-1; 37%), intermediate risk (risk score 2-3; 36%), and poor-risk groups (risk score > or = 4; 27%) with 5-year CR duration rates of 52%, 37%, and 10%, respectively. Conclusions Compared with the previous VAD regimens, Hyper-CVAD was associated with significantly better CR rates, CR duration, and survival. The long-term follow-up results of Hyper-CVAD were favorable. Comparison of Hyper-CVAD with other established adult ALL regimens is warranted.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.20668

Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia

Distinctive Demography, Biology, and Outcome of Acute Myeloid Leukemia and Myelodysplastic Syndrome in Children With Down Syndrome: Children's Cancer Group Studies 2861 and 2891

Mutations in exon 2 of GATA1 are early events in megakaryocytic malignancies associated with trisomy 21.

The overall cure rate for cancer in childhood now exceeds 70% and is projected to reach 85% by the year 2010 in industrialized countries. Therefore, major attention is being placed on reducing the side effects of therapy. However, 85% of the world's children live in developing countries, where access to adequate care often is limited and health status frequently is influenced adversely by prevalent infectious diseases and malnutrition. Despite several confounding factors (different definitions of nutritional status, the wide variety of measures used for its assessment, the selection biases by disease and stage, treatment protocols of variable dose intensity and efficacy, small sample sizes of the studies conducted in the last 20 years), it is accepted that the prevalence of malnutrition at diagnosis averages 50% in children with cancer in developing countries; whereas, in industrialized countries, it is related to the type of tumor and the extent of the disease, ranging from < 10% in patients with standard-risk acute lymphoblastic leukemia to 50% in patients with advanced neuroblastoma. The importance of nutritional status in children with cancer is related to its possible influence on the course of the disease and survival. Some authors have described decreased tolerance of chemotherapy associated with altered metabolism of antineoplastic drugs, increased infection rates, and poor clinical outcome in malnourished children. In this article, the authors review methods of nutritional assessment and the pathogenesis of nutritional morbidity in children with cancer as well as correlations of nutritional status with diagnosis, treatment, and outcome.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.11833

Children, Cancer, and Nutrition-A Dynamic Triangle in Review

The incidence of leukemia is higher in children with Down syndrome (DS) than in normals. In approximately 50% of cases the type of leukemia is acute megakaryoblastic leukemia (AMKL) and it occurs during the first 4 years of life. The leukemic cell also has features of erythroid progenitors and therefore appears to be a precursor cell with biphenotypic properties. In addition, newborns with DS frequently develop transient leukemia (TL), which is characterized by the presence of megakaryoblasts in the blood which disappear during the first 1-3 months of life. The incidence of this disorder is unknown although preliminary studies suggest that megakaryoblasts may be found frequently in the blood of DS newborns. TL does not occur in normal newborn infants. Although TL disappears spontaneously, many of these children will develop AMKL at 1-4 years of age. Recent surveys suggest that 20-30% of newborns with TL will develop AMKL. Preliminary evidence suggests that TL is a clonal proliferation, can be fatal, and may occur in a specific subgroup of DS children. The observations in this report are drawn from our own experience, reports in the literature, and data accumulated in the Canadian Down Syndrome Leukemia Registry.

Leukemia in Down Syndrome: A Review

Megakaryoblastic leukemia and transient leukemia in Down's syndrome have been reviewed using case reports from the literature and our own experience at the Hospital for Sick Children The following conclusions have been reached: (1) approximately 20% of leukemia (excluding transient leukemia) in Down's syndrome is acute megakaryoblastic leukemia; (2) approximately 20% of all leukemia in Down's syndrome is transient leukemia; (3) transient leukemia in Down's syndrome is acute megakaryoblastic leukemia; (4) recurrence of acute megakaryoblastic leukemia occurs in 20% of the cases of transient leukemia; and (5) the incidence of acute megakaryoblastic leukemia in Down's syndrome is estimated to be 400 times that in normal children These observations suggest that a specific form of leukemia, namely acute megakaryoblastic leukemia, has a remarkable association with Down's syndrome

Megakaryoblastic leukemia and Down's syndrome--a review.

We studied the prescription patterns of maintenance therapy for children with acute lymphoblastic leukemia and their association with duration of complete remission. Both 6-mercaptopurine and methotrexate (MTX) were prescribed in doses significantly lower than those recommended (75 mg/m2 daily 6-mercaptopurine; 20 mg/m2 weekly MTX) during maintenance therapy. Of 212 evaluated patients, patients who had relapses (n = 101) received significantly less MTX compared with patients who did not have relapses (n = 111) during the first 2 years of maintenance therapy. In the group of standard-risk patients who received the same induction therapy (n = 92), 11 of 17 who received less than 50% of the recommended MTX dose (64%) and 28 of 75 who received greater than 50% of the dose (37%) had relapses (P less than 0.05). The two groups had comparable periods of interruption of MTX therapy. Further analysis revealed that the lower maintenance dose stemmed from a continuous low prescribed dose and not from more frequent interruption of therapy in relapse. Physicians' inability or failure to adhere to the recommended protocol was associated with a higher relapse rate of acute lymphoblastic leukemia. Improved physicians' compliance may improve the prognosis of the disease.

Marie Peeters

Papers

Megakaryoblastic leukemia and Down's syndrome--a review.

Physician compliance and relapse rates of acute lymphoblastic leukemia in children.