Uri H. Lewinski

Recombinant human erythropoietin in the treatment of multiple myeloma-associated anemia.

UNLABELLED Multiple myeloma (MM) is commonly associated with anemia. Several causes have been implicated but inadequate erythropoietin (Epo) production appears to be important. This single-institute open-label, non-comparative clinical trial was undertaken in order to evaluate serum Epo levels in patients with MM and to study the efficacy and toxicity of recombinant human Epo (rHuEpo) in the treatment of MM-associated anemia. MM patients with a baseline hemoglobin (Hb) level of < 11 g/dl received rHuEpo 150 U/kg 3 times/week subcutaneously, with a possible dose increase to 300 U/kg if no response was observed after 4 weeks. The study was designed for 12 weeks, although some responders continued rHuEpo. The study endpoints were determined by an increase in Hb and a decrease in blood transfusion requirements (BTR). Seventeen patients were enrolled in the study. The median serum Epo level was 150 mU/ml (range 11-232). Four patients did not complete the study for reasons unrelated to rHuEpo, but to their underlying MM. Twelve patients (70.6%) responded with an increase in their Hb levels. One patient (5.9%) responded partially. The median Hb level rose from 9.4 g/dl (range 7.3-10.7) at study commencement to 12.5 g/dl (range 9.0-15.2). Six of the 11 patients who were transfusion dependent enjoyed a complete abolition of BTR. The response was also interpreted as an improved quality of life: 3 patients reported a decrease of 1 level in their WHO performance status (PS) score; in 8 patients, the PS declined by 2 grades and 1 patient enjoyed PS reduction by 4 scores. Six patients continue to receive rHuEpo up to 18 months, with a good response and a smaller maintenance dose. Four patients reported flu-like symptoms, 2 suffered from a local irritation and 1 experienced a transient controlled elevation of blood pressure. SUMMARY (1) Pretreatment endogenous serum Epo levels were relatively low in all patients studied with MM-associated anemia; (2) rHuEpo was well tolerated in these patients; (3) rHuEpo was highly effective in the treatment of anemia in MM, and (4) the response to rHuEpo is characterized by an increase in Hb levels, a reduction in BTR and an improvement in the WHO PS score.

Electron microscopic study of lymphosarcoma cell leukemia

SummaryA patient presenting clinical features of leukemia is described. The morphology of the cells in the peripheral blood and in the bone marrow suggested that they were of the lymphocytic series, but the type of leukemia was uncertain. Electron microscopic studies revealed concentric or spiraloid lamellar formations in the cytoplasm of a substantial number of the cells, suggesting the diagnosis of lymphosarcoma cell leukemia.ZusammenfassungEs wird ein Patient mit klinischen Zeichen einer Leukämie beschrieben. Die Morphologie der Zellen im peripheren Blut und im Knochenmark deutet darauf hin, daß diese der lymphatischen Reihe angehören, jedoch bleibt der Typ der Leukämie unsicher. Elektronenmikroskopische Untersuchung zeigt konzentrische oder spiralförmige lamellare Strukturen im Zytoplasma einer Anzahl dieser Zellen, was auf die Diagnose einer Lymphosarkom-Zell-Leukämie hindeutet.

Satellitism of Platelets to Monocytes.

Satellitism of platelets to monocytes was observed in 3 patients suffering from polycythaemia vera, a myeloproliferative disorder and chronic lymphocytic leukaemia. This phenomenon occurred on cells in the buffy coat obtained from venous blood anticoagulated with heparin. The existence of platelet satellitism was reported to occur mainly to polymorphonuclears, but the present observation, as well as a previous report from our department, indicated that it may also exist to monocytes. Satellitism was achieved either by adherence of the platelets to monocytes, giving the impression of rosette formation, or by fusion of platelet pseudopodia with the monocyte membrane. The importance of this phenomenon in the evaluation of the platelet count using automatic instruments is discussed.

Severe tumor lysis syndrome following splenic irradiation

A 72‐year‐old man suffering from non‐Hodgkins lymphoma is described. After failing to respond to chlorambucil–prednisone regimen for three months, he was treated by splenic irradiation (total dose 500 cGY) in 10 consecutive daily doses. Two days after the last irradiation, the patient developed acute tumor lysis syndrome (TLS) with extreme blood levels of uric acid (33.7 mg/dl), phosphorus (13.7 mg/dl), potassium (6.08 mEq/l), and calcium (6.8 mg/dl). It should be remembered that the acute TLS, which usually occurs following chemotherapy, can also be radiation‐induced. Am. J. Hematol. 60:75–76, 1999.

Ultrastructural features of the plasma cells in "non-secretory" myeloma.

ZusammenfassungBei einem Patienten mit nichtsekretorischem Plasmozytom wurden die Plasmazellen immunologisch und elektronenmikroskopisch untersucht. Die Diagnose beruhte auf dem klinischen Bild, den typischen Röntgenbefunden und einer Infiltration des Knochenmarks durch Plasmozytomzellen, die eine spezifische Immunfiuoreszenz mit Antiseren für IgM und kappa-Leichtketten zeigten. Es wird versucht, das Fehlen des Paraproteins im Serum mit Hilfe der elektronenmikroskopischen VerÄnderungen zu erklÄren. In den Plasmazellen der nichtsekretorischen Myelome wird die Sekretion der Paraproteine wahrscheinlich dadurch verhindert, da\ sie durch Membranfragmente eingeschlossen werden.SummaryA case of “non-secretory” multiple myeloma is described. The diagnosis was based on the clinical picture, typical radiological findings, and infiltration of the bone marrow by myeloma cells which showed specific immuno-fluorescence staining mainly with antisera for IgM and kappa light chains. An attempt is made to explain the absence of pathological proteins in the serum, based on the ultrastructural findings of the myeloma cells, which showed “buddings” of the cell membranes containing endoplasmic reticulum and cytoplasmic material. It is suggested that the cells of the “non-secretory” type of multiple myeloma possess a normal excretory mechanism, but the pathological proteins are prevented to be secreted in the serum being surrounded by portions of the cell membrane.

Two abnormal clones in the bone marrow cells of a patient with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is considered to be a clonal disorder, although most investigations have failed to show chromosomal abnormalities. The present patient suffered from PNH and exhibited in bone marrow cells two abnormal clones with 47 chromosomes in addition to cells with 46 chromosomes. One clone showed trisomy 9, a finding previously reported in leukemias and myeloproliferative disorders. Thus, PNH seems to be a clonal myeloproliferative disease.

Non-random chromosomal aberrations in a complex leukaemic clone of a Bloom's syndrome patient

SummaryBlooms syndrome is one of the congenital disorders known to have increased frequency of acute leukaemia. The complex cytogenetic findings in the leukaemic cells of a 39-year-old male with Blooms syndrome are described. These included a translocation t(7;17), missing 7q and 17p, a reciprocal translocation t(4;22); del 3q, del 8q22, del 20q, missing 12 and missing Y. In the same patient a missing Y had been noted 10 years previously in 15% of his peripheral blood lymphocytes.

Ultrastructural alterations of peripheral blood cells due to Vipera palaestinae snake bite

Abstract The ultra-structural alterations of the circulating red blood cells, lymphocytes and platelets of a patient bitten by a Vipera palaestinae snake were observed with transmission and scanning electron microscopes. The red blood cells showed a marked echinocyte transformation. The lymphocytes revealed shortening and “rarefaction” of their microvilli, as well as decrease in the number of cell organelles. The platelets showed shortened cytoplasmic processes, increased glycogen content, reduced number and abnormal mitochondria. The possible role of venom phospholipase A, as an inducer of some of these alterations is discussed.

Transmission and scanning electron microscopy study on plasma cell leukemia.

SummaryThe peripheral blood cells of a patient with acute plasma cell leukemia were examined with transmission (TEM) and scanning (SEM) electron microscopes. The TEM features of the immature plasma cells comprised lobulated and irregulary shaped nuclei, with scanty heterochromating and bizarre nucleoli, parallel arrays of endoplasmic reticulum, cytoplasmic fibrils and numerous polymorphic mitochondria. SEM examination of the cells showed long, thin irregular ruffles, or round blebs on the cell surface, with appearance different from this observed on other types of leukemia. A remarkable clinical and hematological remission was achieved with administration of melphalan and steroids.ZusammenfassungDie peripheren Blutzellen eines Patienten mit akuter Plasmazell-Leukämie wurden mit Transmissions-(TEM) und Raster-(SEM) Elektronenmikroskopie untersucht. Die unreifen Plasmazellen zeigten im TEM gelappte und irregulär geformte Kerne, mit spärlichem Heterochromatin und bizarren Nukleolen, parallele Anordnung von endoplasmatischem Reticulum, zytoplasmatische Fibrillen und zahlreiche polymorphe Mitochondrien. Im SEM waren dünne, längliche oder Kolben-förmige Auswüchse an der Oberfläche zu sehen, die deutlich von den Auswüchsen an der Oberfläche bei anderen akuten Leukämien abwichen. Eine weitgehende klinische und hämatologische Remission wurde mit der Verabreichung von Melphalan und Corticosteroiden erreicht.

The presence of hepatic intramitochondrial crystalline inclusions in routine liver biopsies.

Electron microscope examination of the liver biopsies of 33 patients revealed the presence of intramitochondrial crystalline inclusions (IMCI) in ten of them. Three patients suffered from iron deficiency anemia, porphyria, and malignant melanoma, conditions not reported to be associated with IMCI. Comparison of the clinical and laboratory findings of patients with and without IMCI did not show significant difference, or a clue for clarifying the nature of this phenomenon. Although these inclusions were reported in normal individuals, the possibility that they are the result of liver damage is not excluded.