Bracha Ramot

Aplastic crisis due to human B19 parvovirus infection in red cell pyrimidine-5'-nucleotidase deficiency.

Two siblings with chronic hemolytic anemia due to red cell pyrimidine-5-nucleotidase (P-5-N) deficiency, presented within a few days of each other with a febrile illness and pancytopenia. The cause of the aplastic crisis was an acute infection with human B19 parvovirus (B19 HPV) as proven by immunoelectron microscopy and DNA hybridization. This is the first report on the association of B19-HPV-related aplastic crisis with P-5-N deficiency.

Naproxen-Associated Fatal Acute Renal Failure in Multiple Myeloma

Ofer Shpilberg, MD, Institute of Hematology, The Chaim Sheba Medical Center, 52621 Tel-Hashomer (Israel) Dear Sir, Nonsteroidal antiinflammatory agents (NSAIDs) including naproxen have become a common and accepted measure for treating fever associated with malignancy including myeloma fever [1,2]. Naproxen as well as other NSAIDs are rarely associated with renal abnormalities such as acute renal failure, sodium retention with edema, hyponatremia, hyperkalemia, nephrotic syndrome and acute interstitial nephritis [3]. Until January 1987, in over 10 years of postmarketing experience with naproxen in the USA and over 1.6 billion patient days’ exposure, only 19 cases of naproxen-associated renal failure have been reported (Syntex Laboratories). Recently Wu et al. [4] described 2 patients with low back and hip pain who developed acute renal failure after 1 week of treatment with the drug. Later, multiple myeloma was diagnosed in these patients. The autors conclude that multiple myeloma should be added to the list of precipitating factors for developing renal failure in patients who are treated with NSAIDs. Other factors include volume depletion, diuretic therapy, heart failure, liver disease and underlying renal failure. We present herein a 62-year-old woman with light chain multiple myeloma, osteolytic lesions and hypercal-cemia diagnosed in 1983. Between 1983 and 1984 she received irradiation to the involved bones and chemotherapy according to the M-2 protocol [5]. In March 1985, she suffered from a febrile disease treated by intravenous gentamycin. This was followed by transient acute renal failure of which the patient soon recovered completely. Since then until August 1988 her renal function tests and urinalysis were normal: serum creatinine 1.0 mg/dl and blood urea nitrogen 32 mg/dl. In August 1988 the patient was admitted to the hospital for a prolonged fever of 38–40¤C. The fever was attributed to the myeloma since comprehensive investigation did not reveal infection, and a therapeutic trial with broad spectrum antibiotics did not result in defervescence. Treatment with naproxen, 1,000 mg/day, was started followed by immediate return of body temperature to normal levels and marked improvement in the patient’s general feeling. Ten days after the initiation of treatment with naproxen, the patient developed asynchronized multiple myoclonic jerks in her face and limbs. Her body temperature was normal; laboratory results revealed signs of acute renal failure: blood urea nitrogen was 265

Familial Aggregation of Nonhematological Malignancies in Relatives of Patients with Hematological Neoplasms

Familial aggregation of nonhematological malignant disorders (NHMD) was compared in 189 families of patients with hematological neoplasms (HN) with a control group of 36 families of patients with benign hematological disorders and a second group of 33 families of patients with diabetes mellitus. A self-administered questionnaire was used requesting from each family a full list of first- and second-degree relatives, their vital status, current age or age at death, and a list of their chronic diseases, including all malignant disorders. There was no evidence of a significantly increased tendency for developing NHMD among relatives of patients with HN as compared to controls (adjusted odds ratio of 0.88; 95% confidence interval 0.61–1.27). Moreover, in the HN group, no significant difference in the frequency of NHMD was found between the families with and without familial aggregation of HN. Based on the present analysis and our previous observations on familial aggregation of HN, we conclude that the increased aggregation of malignant disorders among relatives of patients with HN is unique to the hematopoietic system and might result from a genetic predisposition to HN in these families.

Neoplastic Cell Activation And Proliferative Response To CD40-Ligand Characterize Recurrent Leukemic Bouts In An Unusual Case Of Low Grade Lymphoma

Spontaneous fluctuations in activity of low-grade B cell lymphomas are common but not understood. An explanation may be offered by studying an atypical SLL/CLL case characterized by recurrent cycles of leukemic phase alternating with spontaneous remission (1). During remissions, residual IgMK+ leukemic cells exhibited resting phenotype, low proliferative response to CD40-ligand and delayed apoptosis. In contrast, the acute phase counterparts were phenotypically activated, underwent rapid apoptosis in culture and proliferated extensively in response to membrane-anchored CD40-ligand. Transient bursts of serum TNFa and IL-10 preceded the acute phases, which were characterized by the co-existence of CD40-ligand+ T lymphocytes and lymphoma cells in the bone marrow. Based on ex-vivo and in-vitro data, we suggest that changes in the lymphoma milieu affect the neoplastic cell activation status, rate of proliferation in response to activated T cells and rate of apoptosis. These responses may underlie both the induction and spontaneous regression of the acute phases in this unique lymphoma. Our findings raise the possibility that part of this mechanism may have evolved during transformation of indolent common CLL to its more aggressive form.

Selective Splenectomy in Hodgkin’s Disease, Stages I and II

Sixty-three patients with Hodgkins 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 Hodgkins 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.