Lymphomatous T-cell leukemia in two Arab children. Is there a role for an environmental effect.

Two Arab children from the Gaza strip presented with fever, weakness, hepatosplenomegaly, lymphadenopathy and leukocytosis. The peripheral and bone marrow blasts had an immunophenotype compatable with T-cell acute lymphoblastic leukemia, and exhibited unusual markers (CD2+, CD3+, CD4-, CD8-). Cytogenetic studies revealed t(8;14)(q24;q11), possibly involving the alpha/delta locus of the T-cell receptor gene on chromosome 14 rather than the immunoglobulin heavy-chain locus usually involved in the t(8;14)(q24;q32), which is typical for Burkitt's leukemia/lymphoma. One of the children had a brother who died of T-cell acute lymphoblastic leukemia a few years later, however, his blasts showed deletion of chromosome 12. The possible role for environmental factors associated with low socioeconomic status, as well as of genetic factors in leukemogenesis are discussed.

Postremission therapy with two different dose regimens of cytarabine in adults with acute myelogenous leukemia.

Sixty-seven out of 105 (64%) adults with de novo acute myelogenous leukemia (AML), achieving complete remission after induction chemotherapy, entered two successive postremission treatment protocols. Between 1987 and 1989, 35 patients received an intermediate dose of cytarabine (IDAC) along with other drugs. Between 1990 and 1993, 32 patients received high dose cytarabine (HIDAC) with similar other drugs. Patients treated with IDAC had a median survival of 13.8 months (95% CI 11.2-23.1 months) and a 2 year survival of 34.3 +/- 8.0%. Patients receiving HIDAC had a median survival of 35.5 months (95% CI, lower limit 29.8 months) and a 2 year survival of 71.6 +/- 9.4% (P < 0.002). The 2 year actuarial leukemia-free survival (LFS) was 17.8 +/- 6.6% in the IDAC group and 67.3 +/- 10.0% months in the HIDAC group (P = 0.004). The HIDAC group had a significant 2 year survival advantage over the IDAC group only in patients younger than 45 years. The 2 year survival in the first group was 83.3 +/- 10.8% versus 23.5 +/- 10.3% in the IDAC group (P = 0.0001). In patients older than 45 years, no significant differences in 2 year survival was noticed (52.9 +/- 15.78 versus 44.4 +/- 11.7, P = 0.8). Censoring the 21 patients who underwent bone marrow transplantation (BMT) at BMT did not change significantly the survival analysis of the patients in each group. This study is consistent with previous reports favoring HIDAC intensification in the postremission treatment of young patients with AML.

Salvage therapy of refractory and relapsed acute leukemia with high dose mitoxantrone and high dose cytarabine.

We have assessed the outcome of 66 refractory and relapsed acute leukemia patients treated with high dose mitoxantrone and cytarabine. Therapy consisted of a total dose of 40-60 mg/m2 mitoxantrone and 3 g/m2 of cytarabine daily on 5 consecutive days. A total of 28 patients were treated for primary resistant and 38 patients for early or late relapsed leukemia. A total of 35 patients achieved CR. Four patients died during the induction course. Toxicity was acceptable and comparable to other salvage regimens. The median disease-free and overall survivals were 4 and 6 months, respectively. Although this regimen is effective in achieving remission in refractory leukemia, its duration is short.

Chromosomal aberrations suggestive of mutagen-related leukemia after 21 years of "therapeutic" radon exposure.

A 68-year-old woman with acute myelomonocytic leukemia, who was treated annually for 21 consecutive years by "therapeutic" low-dose radon gas radiation because of spondyloarthritis, is described. The karyotype of the malignant clone was 45,XX, -17, -18,del(5)(q15q33), +t(17;18)(q11.2q23). In 45% of the metaphases, the modal number was between hyperdiploid to near tetraploid. Double minute chromosomes were demonstrated in 60% of the cells. These chromosomal aberrations are suggestive of mutagen-related leukemia.

Translocation (2;14)(p13;q32) in CD10+ ;CD13+ acute lymphatic leukemia.

The rare t(2;14)(p13;q32) was previously described in the three pediatric patients with acute lymphatic leukemia. In these cases this abnormality was found at diagnosis, manifested the sole chromosomal abnormality, and was associated with a favorable prognosis. We here describe three cases of leukemia where such translocations were found at relapse, were associated in two of the cases with additional known characteristic chromosomal aberration, and were associated with a grave prognosis. Interestingly enough, the malignant cells of all three patients shared the same surface antigens: CD34, HLA DR, CD10, CD20, and the myeloid marker CD13. The leukemic clone exhibiting t(2;14) probably evolved from a t(1;19)6q- pre-B acute lymphatic leukemia in one of the cases, and from a chronic phase Ph1 chromosome in another. The significance of the translocation and the coexistence of CD10 and CD13 on the same cell are discussed.

Persistent abnormalities in red cell parameters following treatment of lymphoma.

Patients who have recovered from malignant lymphoma are at an increased risk of secondary acute leukemia (AL), and overt AL is frequently preceded by a myelodysplastic syndrome. Although the statistical risk is significant, only a minority of the patients will be so affected. We have reviewed peripheral blood counts of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) treated in the Departments of Hematology at the Edith Wolfson and Chaim Sheba Medical Centers, Israel. Included were only those who went into a complete remission and remained lymphoma free for extended periods. There were 85 patients with HD and 36 with NHL. In both groups peripheral blood counts at diagnosis were within the normal range. A prolonged follow-up (> 4 y), during which no further treatment was given, revealed a sustained increment over time of MCV (delta MCV) both in HD and NHL. A persistent monocytosis in HD patients was also evident. delta MCV was larger in HD. The difference at the end of the follow-up period was as follows: 10.1 fl + 11.8 in HD vs 5.0 fl + 6.2 in NHL, (P < 0.001). In addition, a significant loss of the normal correlation between the MCV and levels of hemoglobin was seen at the last follow-up. The change in MCV was present in all treatment groups, its magnitude increasing from radiotherapy to chemotherapy to combined radio chemotherapy. This trend is in analogy to the risk of secondary AL which is lower in NHL vs HD. Furthermore, it is lowest post radiotherapy and highest when both treatment modalities are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperglycemia during acute myocardial infarction. A six-year follow-up study.

Fasting blood glucose (FBG) level and oral glucose tolerance (OGT) were determined in 169 patients within 72 hours of an acute myocardial infarction. Elevated FBG levels were found in 47.5% and a reduced OGT in 72.5%. Of 32 patients who died in the hospital, FBG value was elevated in 72% and the OGT was abnormal in 89%. Of 91 patients who survived longer than six years, the initial FBG level had been elevated in 33%, and the OGT had been abnormal in 67%. Eighty percent of the group with initially raised FBG values had either latent or overt diabetes, while more than 95% of the patients with initially normal FBG values had a normal OGT. Fifty-five percent of the patients with abnormal OGT during myocardial infarction showed normal OGT six years later. The FBG level shortly after an acute myocardial infarction is a better guide to prognosis and to the prediction of subsequent development of diabetes mellitus than the OGT test.

The relation between therapy and herpes zoster in Hodgkin's disease.

The rate of occurrence of herpes zoster (HZ) was analyzed by the life table method in 108 Hodgkin's disease (HD) patients, diagnosed and treated during the years 1969 to 1976. Three groups, divided according to the degree of severity of the disease, were compared. The cumulative rate of occurrence of HZ at the end of the third year after diagnosis was higher in the group with intermediately extensive disease than in that with the most extensive disease (35 vs. 23%), but the difference was not significant. At the end of the fifth year, the rate was almost identical in both groups (35.3 and 35.6%, respectively). The group with the least severe form of HD had a very low HZ rate (2.2%), which was significantly different from the other two groups and close to the rate reported for normal populations. The five-year mortality rate was 0.0, 20.3 and 40.6%, respectively, in the three groups. These findings were interpreted to mean that in more advanced stages of HD, therapy and not the severity of the disease is the main factor determining the incidence of HZ. Extended field irradiation followed by a few courses of combined chemotherapy appear to have an effect similar to that of prolonged chemotherapy.

Pretreatment prognostic factors and hospitalization periods in childhood acute lymphoblastic leukemia.

Pretreatment prognostic factors and hospitalization periods were analyzed in 57 consecutive children who had acute lymphoblastic leukemia diagnosed between 1967 and 1977, and who were followed up for at least two years. We investigated possible correlations between white blood cell (WBC) count, organomegaly and mediastinal enlargement at diagnosis, as well as age and sex, with the length of first remission and survival. Children presenting with a combination of all of the following four risk factors--WBC count greater than or equal to 50,000/mm3, enlarged mediastinum, spleen and liver greater than or equal to 3 cm below the costal margin--comprised a poor-prognosis group, in which boys predominated. Age in this small group of patients had no correlation with prognosis. On the other hand, no specific risk factor was predictive for survival in the 48 children who had less than four of the risk factors. In this better-prognosis group, children less than 2 yr and greater than 10 yr had a higher relapse rate than those of intermediate ages, and girls had a significantly better prognosis than boys. These results indicate that age and sex are intercorrelated with the above risk factors, so that analysis of the effect of a single risk factor or even a combination of two factors can be misleading. In the light of these findings, an interpretation of the discrepancies in the literature is suggested. Of interest, too, is the poor prognosis and the high frequency of T-cell leukemia among Arab children. Finally, we stress the importance of day-care facilities that enable shorter hospitalization periods and improve the quality of life.

Autoimmune hemolytic anemia as the presenting manifestation of malignant thymoma.

Severe autoimmune hemolytic anemia is described as the presenting manifestation of malignant thymoma. The hemoglobin level was 5.7 g/dl, the direct IgG antiglobulin test (direct Coombs' test) was strongly positive and the indirect Coombs' test was weakly positive. Prompt remission of the hemolytic process was achieved by thymectomy combined with corticosteroid therapy; the hemoglobin level rose to 12.2 g/dl and both the direct and indirect Coombs' tests became negative. To our knowledge, this is the first case to be described in which autoimmune hemolytic anemia was the presenting manifestation of malignant thymoma. Autoimmune hemolytic anemia may be considered as a manifestation associated with malignant thymoma.

Translocation t(3;17)(q23;q21): a new translocation in acute lymphoblastic leukaemia.

We report on two adult patients with CD10+ positive acute lymphoblastic leukaemia (ALL) who presented with similar clinical and laboratory features and with a new chromosomal translocation: t(3;17)(q23;q21). This translocation may be involved in the formation of a new chimaeric transcription factor. Both patients shared several poor prognostic factors at presentation and an adverse clinical course. The t(3;17)(q23;q21) translocation may therefore predict a poor outcome in ALL.

Therapy with thalidomide in refractory multiple myeloma patients - the revival of an old drug.

We have treated 17 refractory or relapsed multiple myeloma patients resistant to chemotherapy with thalidomide at a dose of 200-800 mg/day. Eleven patients responded, five of whom had a very good partial response (> 75% decline in M protein) and another five exhibited a partial response (> 50% decline in M protein). Except for one patient, treatment was well tolerated with only mild side-effects. Thalidomide should be included in the therapeutic options for refractory myeloma.

Selective splenectomy in Hodgkin's disease, stages I and II. Results of treatment.

Sixty-three patients with Hodgkin's disease, in stages I or II, asymptomatic (A) or symptomatic (B), were diagnosed and followed at the Chaim Sheba Medical Center from 1969 to 1976. Only 14 were staged pathologically. Until 1971, the patients received mantle or "inverted Y" therapy only; thereafter, an extended field that included mantle, upper abdomen and spleen irradiation was given. Symptomatic patients, as well as patients with extranodal involvement, received MOPP chemotherapy (nitrogen mustard, vincristine, procarbazine and prednisone) after termination of radiotherapy. Of 51 patients who were in stage IA or IIA, six relapsed 20 to 43 months after irradiation. Three had a pelvic recurrence; two of them were surgically staged. Thus, in only 1 of 51 patients could staging laparotomy possibly have detected pelvic disease and resulted in different therapy. Our results suggest that total nodal irradiation and staging laparotomy are not mandatory in stages IA and IIA of Hodgkin's disease. The group of 12 symptomatic patients is too small to allow us to draw definite conclusions as to the role of staging laparotomy and adjuvant chemotherapy. However, in view of the high relapse rate in the upstaged symptomatic patients, it seems that chemotherapy should be given to these patients.

Molecular analysis of Burkitt's leukemia in two hemophilic brothers with AIDS.

In two hemophilic brothers infected by the human immunodeficiency virus (HIV), Burkitt's leukemia developed within 1 year. Both patients were treated by aggressive chemotherapy, and both are still in complete remission for 23 and 14 months, respectively. Sera from both brothers contained anti-HIV antibodies. However, DNA extracted from the tumor cells, when analyzed by Southern blot using a cloned HIV probe, did not reveal HIV-related sequences. Hybridization experiments with an Epstein-Barr virus (EBV) probe revealed the presence of EBV-specific sequences in the tumors' DNA. In both patients' tumors rearranged c-myc genes were found. The rearrangements occurred in both genes 3' to the third exon of c-myc, thereby suggesting that a variant chromosomal translocation took place in both cases. Indeed, karyotype analysis of the malignant cells of one of the patients revealed the variant t(2:8) translocation. In contrast to the majority of Burkitt's tumors carrying this translocation, which are kappa light-chain producers, cells of our patient expressed lambda chains. Furthermore, in both cases the lymphoblasts carried IgG on the surface, again an unusual finding in Burkitt's tumors. Finally, because both patients had an identical HLA phenotype, the role of genetic factors in the development of such tumors should be considered.