Aliza Zeidman

Erythropoietin has an anti-myeloma effect - a hypothesis based on a clinical observation supported by animal studies

Recombinant human erythropoietin (rHuEpo) was introduced into clinical practice more than a decade ago, and has been found to be effective in the treatment of several types of anemia, including anemia of end‐stage renal failure and cancer‐related anemia. No study has suggested that Epo might have an effect on the biology of the disease, nor any survival advantage to cancer patients treated with Epo for anemia has been reported. Here we report six patients with advanced multiple myeloma (MM) with very poor prognostic features, whose expected survival was <6u2003months. All six patients were treated with rHuEpo for their anemia, either without any chemotherapy or very mild chemotherapy for a short time. Yet, surprisingly they lived for 45–133u2003months totally from MM diagnosis and 38–94u2003months with rHuEpo (with a good quality of life). In fact, one patient, is still alive and well, more than 8u2003yr after chemotherapy was discontinued because of a resistant aggressive disease. The course in these six MM patients led us to hypothesize that Epo might have an antineoplastic or antimyeloma effect. We proceeded and tested that hypothesis in mouse models of myeloma (Mittelman M et al., Proc Natl Acad Sci USA 98:5181,2001). In these models we confirmed that rHuEpo induced tumor regression in about 50% of the BALB/c mice inoculated with MOPC‐315 myeloma cells. We then presented evidence that the mechanism is a new immune‐mediated phenomenon, via activation of CD8+ T cells. Furthermore, evidence from the literature supports the antineoplastic effect of Epo. Epo might be used as an adjunct immune treatment in various malignant diseases, in addition to the current regimens and chemotherapeutic protocols. Fututre trials should determine the role of Epo in myeloma and cancer treatment, besides clarifying concerns about the presence of Epo receptors on some tumor cells.

Fulminant Intravascular Lymphoma Presenting as Fever of Unknown Origin

Intravascular large cell lymphoma (IVLL) is a rare neoplasm characterized by the proliferation of malignant lymphoid cells within the lumens of small to medium-sized blood vessels. The central nervous system, skin, and endocrine systems are most commonly involved. IVLL may disseminate to the heart, pancreas, liver, spleen, kidneys, and adrenal glands. We report a 52-year-old patient who was admitted for fever of unknown origin for 3 weeks, jaundice and abnormal liver function tests. Fever, high levels of bilirubin, severe anemia, thrombocytopenia, and a very fulminant course characterized the clinical picture. Although bone marrow involvement is quite rare, the diagnosis of IVLL in this patient was done by bone marrow biopsy. The patient was treated with CHOP protocol and received the first course but the aggressive disease led to the patients death.

Morphological changes in peri-prostatic sympathetic ganglion cells in aging males

A significant part of morbidity in elderly male patients involves the pelvic organs and their autonomic neural regulation. The aim of the current study was to report the histopathological changes in the peri-prostatic ganglia in elderly males. The sympathetic ganglia from 36 prostatectomy specimens, 26 due to carcinoma of the prostate and 10 prostates from total cystectomies for transitional cell carcinoma, were examined. The age range was 54-88 years. A total of 5,075 ganglion cells were counted in all the specimens. Pathological changes were identified in 1,696 neuron cells as follows: Neuronophagia in 746 neuron cells, neuron cell vacuolization (330 cells), satellite cells vacuolization (423 cells), cell pyknosis (148 cells) and nageotte nodules (49 cells). A number of these changes increased with age. All the changes were more marked in the peri-prostatic ganglion cells of patients with prostatic adenocarcinoma compared with those with benign prostate hyperplasia, which may be due to local environmental changes associated with the presence of malignancy.

Kaposi's sarcoma associated with Castleman's disease.

To the Editor: Angiofollicular lymph node hyperplasia (Castleman’s disease) is characterized by fever, weakness, weight loss, lymphadenopathy, anemia and hyperglobulinemia (1, 2); however, the histologic picture differs from that of classical lymphoma (3-5). Kaposi’s sarcoma (KS) is an angioproliferative disease with unknown etiology (6). The disease is common in males and usually presents as a skin lesion, but may also involve visceral organs such as lungs, gastrointestinal tract and lymph nodes. We report three patients with lymphoproliferative diseases, two with Castleman’s disease and the other one with non-Hodgkin’s lymphoma, who developed HIV negative KS. The histologic evaluation revealed highly vascular hyperplasia resembling the findings in the lymph node biopsies and suggesting a possible association between KS and lymphoproliferative disorders.