Edwin N. Forman

Effect of L-asparaginase administration on coagulation and platelet function in children with leukemia.

The use of L-asparaginase during remission induction in patients with leukemia is associated with coagulation abnormalities, which may present either as thrombosis or hemorrhage. However, because of the multiple pharmacologic and hematologic variables present in these patients, the exact contribution of L-asparaginase to these coagulation abnormalities is unclear. We studied platelet function and plasma coagulation parameters in 12 pediatric patients with acute lymphoblastic leukemia (ALL) receiving daily L-asparaginase as a single agent when in complete remission. Changes in the prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen, while statistically significant, remained within or close to the normal range during the study. Platelet function also remained normal during the study. In contrast, levels of protein C antigen decreased to a mean of 42%, a significant change from pretreatment values. Levels of antithrombin III (AT III) were likewise depressed to 15 mg/dL (34% of pretreatment value). Despite these changes in the levels of physiologic inhibitors of coagulation, this schedule of L-asparaginase administration was associated with only rare clinical thrombosis, and this study suggests that the development of this complication may be dependent on the presence of additional factors.

Socioeconomic evaluation of a state-funded comprehensive hemophilia-care program.

To assess the effectiveness, cost, and socioeconomic gains associated with a comprehensive state-funded hemophilia program, we compared data from a three-year experience with such a program in Rhode Island with those from the preceding year. Self-treatment, integration of children into school, and achieving satisfying employment of adults are the main goals of the program. During the most recent year, 77 per cent of the patients with severe hemophilia in the state received total care through the Hemophilia Center. Twenty-eight of the 43 patients now treat themselves, the annual number of hospital days per patient has decreased from 12.6 to 3.5, and the number of visits to hospital facilities has fallen from 34 to 2.4, while the yearly cost of clotting factor per patient has remained about

Guidelines for Research

7,000. Altogether, this has saved more than

Limb defects and congenital anomalies of the genitalia in an infant with homozygous α‐thalassemia

10,000 each year for treatment, despite the cost of rehabilitative surgery. Numbers of days lost from school and work have decreased twofold and threefold, respectively. Best of all, comprehensive care has vastly improved the quality of life for patients with hemophilia in Rhode Island.

Y Chromosome Loss in Childhood Leukaemias

“Is this Dr. Stickman? This is Mrs. Osgood. I’m chairperson of the school committee. We have something we’d like to ask your advice about.”

Use of the platelet histogram maximum in evaluating thrombocytopenia

We describe an infant with homozygous alpha-thalassemia, genital abnormalities, and terminal transverse limb defects, whose limbs demonstrate evidence of loss of tissue and abnormal morphogenesis. We propose these defects were due to either severe fetal anemia or to vascular occlusion by abnormal erythrocytes, resulting in hypoxia of the developing distal limbs and genitalia.

Predictive sensitivity of human cancer cells in vivo using semipermeable polysulfone fibers.

Summary. During the past 3½ years cytogenetic studies have been performed on all children with leukaemia prior to treatment. Loss of the Y chromosome documented by chromosome banding techniques, was observed in bone marrow blast cells from two of 11 consecutive male children. One patient had acute myeloblastic leukaemia of t(8;21) type. The other patient was diagnosed as acute lymphoblastic leukaemia. Our studies provide evidence that Y loss occurs in childhood leukaemias and is not necessarily related to an ageing process as suggested by others. Furthermore, this study demonstrates that Y loss can occur as a sole abnormality in non‐myeloid leukaemia.

Research as Therapy

The purpose of this study was to compare the mean platelet volume (MPV) and the highest peak of the platelet volume distribution curve (maximum of the platelet histogram) with regard to their ability to discriminate between thrombocytopenia due to decreased platelet production or increased platelet destruction. A total of 156 children were studied. Twenty‐eight had a diagnosis of idiopathic thrombocytopenic purpura (ITP) and 128 had a low platelet count due to decreased production. MPV and maximum of the platelet histogram were obtained by using the Coulter Counter Max M (Coulter Diagnostics, Hialeah, FL). A comparison of the sensitivity and specificity for the MPV and the maximum of the histogram has been made using the method of the receiver operating characteristic curves. The results show that the maximum of the histogram is superior to the MPV and is a highly effective test for the evaluation of thrombocytopenia. We recommend the use of the maximum rather than the MPV to help distinguish between ITP and thrombocytopenia secondary to decreased platelet production. Am. J. Hematol. 60:19–23, 1999.

Changing a Lifestyle

An in vivo experimental model was developed to predict efficiently and accurately chemosensitivity of human tumors. Human cancer cells either from cultured cell lines or from patients’ tumors were injected directly into semipermeable polysulfone fibers subsequently implanted into immunocompetent rats. Results suggest utility of this novel model system for predicting tumor sensitivity to a wide range of anticancer agents and for potentially guiding the treatment of cancer patients in the clinical setting.

“Ordering Up” Medical Care

“Now that you know that it’s acute leukemia, you have to decide where you want to take your son for treatment.”