Heavy-chain immunoglobulin gene rearrangement and cytoplasmic immunoglobulin expression in acute monocytic leukemia following primary germ cell tumor.

A case of acute monocytic leukemia with rearrangement of the immunoglobulin heavy-chain gene and strong cytoplasmic immunoglobulin expression in a young patient treated with multi-drug chemotherapy for primary seminomatous germ cell tumor 13 months earlier is reported. The short latency period from the beginning of therapy for primary germ cell tumor and the abrupt onset of leukemia with no identifiable prodrome bear similarities to podophyllotoxin-related leukemias.

Radiolabeled octreotide for the demonstration of somatostatin receptors in malignant lymphoma and lymphadenopathy.

UNLABELLED: This prospective study evaluated somatostatin receptor-specific scintigraphy as a clinical tool for routine detection of malignant lymphoma. METHODS: Forty-one consecutive patients were examined using 111In-DTPA-D-Phe-1-octreotide. Thirty-four patients had diagnoses of Hodgkin's disease (n = 11) or non-Hodgkin's lymphoma (n = 23) previously verified and staged by hematology, histology and imaging methods (CT, chest x-ray and abdominal ultrasonography). The remaining seven patients initially suspected of presenting lymphoma (n = 5) or lymphoma recurrence after chemotherapy and radiotherapy (n = 2) were subsequently shown to have other diseases. Planar images were recorded 4, 24 and 48 hr after intravenous injection and evaluated without knowledge of other results. In case of negative planar scintigraphy, additional SPECT images were obtained. Since these failed to increase sensitivity, they were omitted after 15 negative recordings. RESULTS: Octreotide scintigraphy did not yield false-positive results. The sensitivity for detecting Hodgkin's disease was 70% and varied from 88% in the neck and chest to 13% in the abdomen and pelvis. The sensitivity for non-Hodgkin's lymphoma was not influenced by localization and amounted uniformly to 35% but varied with the degree of malignancy between 44% (high-grade) and 29% (low-grade malignancy). CONCLUSION: Our results suggest that radiolabeled octreotide is better suited to characterize somatostatin receptor expressing lymphomas than to localize lesion sites. It is useful for imaging Hodgkin's disease, especially above the diaphragm.

No evidence for microsatellite instability or consistent loss of heterozygosity at selected loci in chronic myeloid leukaemia blast crisis.

The aim of the present study was to investigate loss of heterozygosity (LOH) or microsatellite instability in chronic myeloid leukaemia (CML) blast crisis at genomic locations which are known or postulated to harbour tumour suppressor genes. We studied 48 patients in blast crisis of myeloid (n = 31), lymphoid (n = 15), megakaryocytic (n = 1), or mixed lineage (n = 1) phenotype by comparing constitutional DNA extracted from buccal epithelial cells or chronic phase leucocytes with DNA obtained from blast crisis leucocytes. Twelve variable number tandem repeat loci from six different chromosomes were amplified by polymerase chain reaction using labelled primers, and fractionated on polyacrylamide gels. After autoradiography, length as well as intensity of the amplified products were compared between constitutional and blast crisis samples. LOH was scored as complete, partial or none in informative patients. Complete LOH was found in one patient at 8p22 and another at 13q14; partial LOH was detected in three patients at 11p13 and/or 11p15. No LOH was found at 6q27, 8p21, 18q21, 22q11-12 and 22q13 in any patient. Furthermore, no consistent difference in allelic length was observed in 517 paired amplifications indicating no microsatellite instability. We conclude that the Rb gene at 13q14, the Wilms tumour gene at 11p13, the DCC gene at 18q21, the neurofibromatosis 2 gene at 22q11-13 and uncloned tumour suppressor genes at 6q27, 8p21-22 and 11p15, as well as genes responsible for microsatellite instability, are unlikely to be involved in the progression of CML to blast crisis in the majority of patients.

Bone marrow lymphocyte subsets in myelodysplastic syndromes.

AIM: To examine lymphocyte subsets in patients with myelodysplastic syndromes (MDS); and to correlate immunohistological variables with prognosis. METHODS: Bone marrow trephine biopsy specimens from 65 patients with MDS were immunophenotyped using a panel of antibodies. A minimum of 1000 cells from representative areas of marrow sections were counted at light microscopy. The association between immunohistological variables and prognosis was assessed. RESULTS: Compared with normal control marrows (n = 23) no major abnormalities of T cells (CD3), T cell subsets (CD4, CD8, CD25, TCR gamma/delta) or natural killer cells (CD56, CD57) were seen in the 65 patients. In high risk MDS (RAEB, RAEB-t) 19% of the cases showed increased numbers of B lymphocytes compared with none in the low risk group (RA, RARS) (p < 0.0090). Only percentages of B cells above 3% significantly correlated with poor survival (p = 0.0121 for CD19, p = 0.046 for CD22). CONCLUSIONS: The deviations in T lymphocyte counts seen in peripheral blood and in bone marrow aspirates could not be verified in bone marrow biopsy specimens.

Suppression of chronic lymphocytic leukaemia by megakaryocytic myelosis.

In a 77-year-old Caucasian female B-cell chronic lymphocytic leukaemia was diagnosed and classified as stage 1 according to the Rai classification. The disease remained stable and therefore no antileukaemic therapy had to be initiated. Four years after the initial diagnosis the patient developed hepatosplenomegaly, anaemia and leukopenia. Bone marrow biopsy revealed megakaryocytic myelosis supervening upon the pre-existing chronic lymphocytic leukaemia.

Treatment of 11 patients with chronic myelogenous leukemia with interferon-alpha-2C and low-dose cytosine arabinoside.

Patients with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) and on interferon (IFN)-alpha-2c treatment for at least two months were entered in the present pilot study. IFN-alpha treatment was maintained identically and cytosine arabinoside (Ara-C) was added at monthly cycles of 10 mg/m2/day for ten days subcutaneously. In the case of a leukocyte nadir above 10 G/l, the Ara-C dose was increased to 20 mg/m2/day for 10 days per month. Ten of the eleven patients entered in this study were evaluable for toxicity and response. They received a total of 87 IFN-alpha/Ara-C cycles (3-14/patient). Five patients received 1-5 cycles with Ara-C dose intensification to 20 mg/m2/day. The following gastrointestinal and hematological toxicities were attributable to Ara-C, as they had not been observed in these patients during the preceding IFN-alpha monotherapy period. Gastrointestinal side effects consisted of nausea grade 1 (n = 5) and diarrhea grade 2 (n = 1). Hematotoxicity was observed in eight patients, grade 1 in five patients and grades 2, 3 and 4 in one of the patients each. Both episodes of grades 3 and 4 toxicity were seen during dose escalation to 20 mg/m2. Small cytogenetic responses (4-14%) were observed in 3 patients and a larger one (50%) in one patient, hematological improvement or stable disease in an additional three patients. These preliminary data suggest that the combination of IFN-alpha and low-dose Ara-C is active in inducing cytogenetic responses in CML patients at an acceptable rate of toxicity and therefore warrant further investigation.

Treatment of anemia in inflammatory bowel disease with recombinant human erythropoietin: results in three patients.

Inflammatory bowel disease (IBD) is often associated with anemia. Of 85 patients with IBD, 28 were anemic and had an inadequately low plasma erythropoietin (EPO) concentration. Three patients with a long-standing history of IBD and refractory chronic anemia (hemoglobin values < 10 g/dL, plasma EPO concentrations below 100 mU/mL) were treated with recombinant human EPO, which was administered subcutaneously three times per week at a dose of 200-300 U/kg of body weight. Bone marrow biopsy specimens taken before therapy showed slightly decreased erythropoiesis with a shift of erythroid precursors toward more immature stages. EPO treatment resulted in a marked increase in hemoglobin values in all 3 patients. Bone marrow biopsies after EPO therapy showed quantitatively and qualitatively normal erythropoiesis in all of them. Correction of anemia was followed by improved well-being, and all patients were able to cope much better with their IBD. In all three patients, there was an increase in body weight and their Karnofsky index improved. After a complete workup and exclusion of any other cause for anemia, erythropoietin treatment, although expensive, should be considered in patients with IBD and refractory anemia.

Successful treatment of primary adrenal insufficiency due to malignant non-Hodgkin's lymphoma.

Although the adrenal glands are frequently the site of tumor metastases, adrenal insufficiency is exceedingly rare. We report on a patient with high-grade B-cell centroblastic lymphoma who initially presented with right axillary lymphadenopathy and bilateral adrenal masses. Four months after axillary lymphadenectomy the patient developed overt signs of Addison's disease. He recovered promptly after initiation of hormone replacement therapy and bilateral adrenalectomy. At present, 16 months after additional chemo- and radiation therapy the patient is considered free of tumor. To our knowledge this is the first report on a patient who presented with adrenal insufficiency in the course of non-Hodgkin's lymphoma and who was successfully treated. Demonstrating this case, we would also like to stress that the development of adrenal insufficiency does not necessarily indicate widespread tumor manifestation in patients with non-Hodgkin's lymphoma.