Julie Blatt

Reduced pulsatile growth hormone secretion in children after therapy for acute lymphoblastic leukemia.

Basal growth hormone levels were measured every 20 minutes over 24 hours in eight long-term survivors of acute lymphoblastic leukemia and in 13 age- and pubertal stage-matched normal children. Among the patients, the median total basal growth hormone output (AUC) was 43 units, compared with 341 units in the normal control group (P less than 0.001). In the patients, mean pulse amplitude (6.9 ng/ml) and frequency (4.6) over 24 hours also were reduced, compared with the control values (32 ng/ml and 8.5, P less than 0.001 and P less than 0.05, respectively). In addition, normal children secreted more GH at night (median AUC 280) than during the day (113, P less than 0.001). However, this diurnal pattern was absent in three of the patients studied. These data suggest that perturbations of spontaneous pulsatile GH secretion are common after standard therapy for ALL and may be a sensitive means of detecting therapy-related neuroendocrine damage. Blunting of spontaneous pulsatile GH secretion may contribute to the abnormalities in growth seen in children with ALL.

Pregnancy outcome following cancer chemotherapy

The outcome of pregnancies of patients who received aggressive chemotherapy was examined. Of 448 patients screened, 30 had 12 abortions (10 elective and two spontaneous) and 28 live births. Follow-up of off spring revealed no major malformations. In addition, growth, development and school performance were normal. These results support the contention that chemotherapy administered to women prior to gestation or after the first trimester may result in normal births in the majority of cases. Moreover, the available data suggest that chemotherapy given to men at or prior to the time of conception does not appear to result in fetal damage. These results may be of value in counseling cancer patients regarding risks to their offspring.

Testicular Function in Boys after Chemotherapy for Acute Lymphoblastic Leukemia

Fourteen boys with acute lymphoblastic leukemia who had been treated with combination chemotherapy (prednisone, vincristine, methotrexate, and 6-mercaptopurine) were followed prospectively to assess the effect of this regimen on gonadal function. At the start of therapy, nine patients were prepubertal, four were intrapubertal, and one was sexually mature. The interval between discontinuation of chemotherapy and the most recent endocrine evaluation ranged from two months to 8 1/2 years (median, 5 1/2 years). Throughout the follow-up period, all patients had normal testicular function as determined by Tanner staging at physical examination and by serum gonadotropin and testosterone levels. Semen samples from six patients were unremarkable except for one sperm count that fell in the low-normal range. These results indicate that the administration of antileukemic chemotherapy can be compatible with normal gonadal development.

Purine pathway enzymes in the circulating malignant cells of patients with cutaneous T-cell lymphoma.

Summary. The activities of three purine pathway enzymes—adenosine deaminase (ADA), 5′‐nucleotidase (5′N) and purine nucleoside phosphorylase (PNP)—were examined in the circulating malignant cells (Sezary cells) of eight patients with cutaneous T‐cell lymphoma (CTCL). Cell lines derived from two other patients with CTCL were also studied. These were compared with enzyme activities in peripheral blood T‐lymphocytes from 11 normal donors and six samples of human thymocytes. ADA activities were similar in the Sezary cells and peripheral blood T‐cells (medians 7 U and 15 U, P=0.14), and both of these groups demonstrated significantly lower activity than did the thymocytes (median 100 U, P=0.002). 5′N activity in the Sezary cells was also similar to that of the T‐lymphocytes (median 0.022 U and 0.030 U, P>0.05) and both of these groups had significantly greater activity than did the thymocytes (median 0.002 U, P=0.001). Median PNP activity in the Sezary cell population was also comparable to that measured in normal T‐cells. These findings suggest there is a characteristic purine pathway enzyme pattern in Sezary cells that is similar to that seen in normal T‐lymphocytes. This pattern is clearly distinguishable from that of thymocytes and from that previously described in lymphoblasts from patients with T‐cell acute lymphoblastic leukaemia. These results support the concept that Sezary cells are well‐differentiated with respect to the T‐cell axis. Quantitation of purine pathway enzymes may be useful in defining subsets of T‐cell malignancy.

Pancytopenia and vacuolation of marrow precursors associated with necrotizing encephalopathy

Subacute necrotizing encephalopathy (SNE) or Leigh disease is an autosomal recessive disorder associated with various defects of oxidative phosphorylation. Two reports have described the concurrence of SNE with pancytopenia and vacuolation of bone marrow precursors, and have raised the possibility that this symptom complex may be part of a spectrum of diseases which includes Pearsons syndrome (vacuolation of bone marrow precursors, sideroblastic anaemia, exocrine pancreatic dysfunction). We describe a case of Pearsons syndrome in which haematological manifestations antedated progressive neurological deterioration by several years. Cytogenetic studies showed an inverted duplication of chromosome 9 (qh) [inv dup (9) (qh)]. We suggest that cytopenia associated with vacuolation of bone marrow precursors even without clinically apparent central nervous system pathology should prompt consideration of SNE, or related diseases. Conversely, a diagnosis of SNE should prompt evaluation of other organ system functions including bone marrow. Cytogenetic evaluation of other patients with SNE may determine whether the 9 (qh) findings are pathogenetic.