Anton H. Sutor

Early deaths due to hemorrhage and leukostasis in childhood acute myelogenous leukemia. Associations with hyperleukocytosis and acute monocytic leukemia.

There were 294 children with acute myelogenous leukemia (AML) entered into the German AML Berlin, Frankfurt, and Münster hospitals (BFM) 78 and 83 studies. Thirty (10%) died as a result of hemorrhage and/or leukostasis prior to or in the first 12 days of therapy. The risk of early death due to hemorrhage and/or leukostasis is significantly greater when certain features are initially present: acute monocytic leukemia (French‐American‐British [FAB] M5), hyperleukocytosis (⩾100,000/μl), and extramedullary organ involvement (P < 0.001). The risk increases sharply when these factors exist in combination: 72% mortality with FAB M5 and hyperleukocytosis, and 43% with FAB M5 and extramedullary organ involvement. In 11 patients leukostasis alone or in combination with hemorrhage was probably the cause of death during the first 3 days after diagnosis. All 11 children presented with hyperleukocytosis and were classified as monocytic subtype FAB M4 or M5. After induction, a close temporal association between rapid blast reduction and occurrence of fatal hemorrhage was established in five patients. Thrombocytopenic hemorrhages were controllable and, therefore, responsible for death only in exceptional cases. It is difficult to avoid these early fatal complications with current therapeutic measures. Early exchange transfusion together with special supportive care may be useful.

Identification of a candidate missense mutation in a family with von Willebrand disease type IIC

A screening project to identify candidate molecular defects causing von Willebrand disease type IIC (VWD IIC) in a German family was carried out using polymerase chain reaction (PCR) amplification of all 52 exons of the von Willebrand factor (VWF) gene, subsequent electrophoresis of single and double stranded DNA and direct sequencing of PCR products with aberrant electrophoretic patterns. Only one candidate mutation, G550R, caused by a G→A transition, was detected in exon 14 of the pro-VWF gene sequence. This mutation was not found on 200 chromosomes of normal individuals. The propositus was homozygous for the mutation and for an extended intragenic haplotype, composed of eight polymorphic markers. Further family members were heterozygous for the mutation and were phenotypically normal or only mildly affected, in accordance with the recessive pattern of inheritance for VWD type IIC. The mutation could influence one of the presumed active centers for the suspected multimerizing enzymatic activity of pro-VWF localized in the D1 and D2 domain, which corresponds to exon 5 and exon 14 of the VWF gene.

Bilateral renal vein thrombosis and venous sinus thrombosis in a neonate with factor V mutation (FV Leiden)

Bilateral renal vein thrombosis and venous sinus thrombosis were diagnosed within 3 weeks of birth in a full-term neonate. Heterozygosity for a factor V mutation leading to resistance against the anticoagulatory properties of activated protein C was found. Heparin therapy led to resolution of the thrombotic manifestations. With long-term oral anticoagulation, no relapse or other thrombotic event occurred during infancy.

The Problem of Early Death in Childhood AML

In the last 10 years the treatment results of childhood AML have been improved by intensification of chemotherapy and better supportive care. However, approximately 10%–15% of children could not receive adequate chemotherapy because of early death (ED) prior to or during the first 6 weeks of therapy.

Improved Results in Treatment of Acute Myelogenous Leukemia in Children — Report of the German Cooperative AML Study BFM-78

Recently the treatment programs for childhood acute myeloid leukemia (AML) have become more effective, not only in achieving a higher percentage of induction responses but also in the improvement of duration of the first remission [7, 9, 12], Because AML in children is rare — about 80 new cases per year are expected in West Germany and West Berlin – it is necessary to cooperate in multicenter trials to gain experience and to establish the value of new therapies.