Miriam Quitt

Primary hepatic lymphoma presenting as symptomatic immune thrombocytopenic purpura

A 33‐year old Arabian man presented with idiopathic thrombocytopenic purpura that did not respond to steroid treatment or splenectomy. A routine liver scan performed after splenectomy showed a large mass in the liver. Four years later, massive gastrointestinal bleeding led to an emergency laparotomy, which revealed well‐differentiated lymphocytic lymphoma extending from the liver to the fundus and lesser curvature of the stomach. A partial gastrectomy was performed. With chemotherapy the liver mass resolved and the platelet counts have normalized for the past 30 months.

Clodronate in myelofibrosis: a case report.

A 59-year-old man had well-documented agnogenic myeloid metaplasia (AMM) with pancytopenia. Frequent blood transfusions were required over a 10-month period. Androgen therapy was not beneficial and treatment with interferon resulted in severe thrombocytopenia with no decrease in transfusion requirements. Treatment with clodronate at a daily oral dose of 30 mg/kg resulted in a marked decrease in bone marrow fibrosis, and gradual normalization of blood counts over an 8-month period. He has been transfusion independent for the last 33 months. We support the findings of a previous case report that oral bisphosphonate therapy may be of value in patients with AMM.

Reduced natural killer activity in patients with Fanconi's anemia and in family members

Natural killer (NK) activity was measured in the peripheral blood of a family with Fanconis anemia (FA) and compared to normal controls. One of two children with FA, and 6 of 11 family members had reduced NK activity (less than 30% with an E:T ratio of 25:1) compared to none of 40 controls (p less than 0.001). On retesting 5 of 8 family members and both children with FA had reduced endogenous NK activity compared to 0 of 5 controls (p less than 0.02). The number of NK cells determined by Leu 11b antibody was not reduced in any of the family members. Augmentation with interleukin-2 (IL-2) and alpha interferon (IFN) in those with low endogenous activity was variable. Three demonstrated no response to the 2 immunomodulators, while the 4 others increased to low normal levels. We conclude that some patients with FA and their apparently healthy relatives have reduced NK activity, which appears to be secondary to an intrinsic cell defect.

Increased spontaneous secretion of IL-6 from B cells of patients with B chronic lymphatic leukaemia (B-CLL) and autoimmunity

We studied B cells from 18 patients with B‐CLL, six of them with autoimmune haemolytic anaemia, for spontaneous secretion of IL‐6. Our aim was to determine whether the increased incidence of autoimmune disease found in B‐CLL patients is associated with enhanced spontaneous IL‐6 secretion. IL‐6 was measured by the effect of B cell supernatants on the proliferation of an IL‐6 dependent plasmacytoma cell line T1165. The highest IL‐6 values (7.4±1.8 U/ml) were measured in supernatants derived on day 3 of culture from lymphocytes of the six patients with B‐CLL and concomitant autoimmune disease. The maximal IL‐6 values for 10 patients with B‐CLL only were 2.8±0.3 U/ml and for 10 age‐matched controls, 0.8±0.3 U/ml (P < 0.01, each group compared with the other). We conclude that there is an association between B‐CLL, autoimmune disease and the spontaneous in vitro secretion of IL‐6. Further studies are needed to determine whether the IL‐6 secretion plays a role in the pathogenesis of autoimmune disease in patients with B‐CLL.

Multiple myeloma in the geriatric patient

Consecutive patients with multiple myeloma were studied. The clinical characteristics and survival of 17 patients aged 75 years or more were compared to 42 patients younger than 75 years of age. Of the patients older than 75 years, 14/17 (82%) died in less than 12 months compared to only 11/42 (26%) of those under 75 years old (P < 0.001). Multivariate analysis showed that both age and hemoglobin were significant predictors of survival (P < 0.012 and P < 0.002, respectively) explaining 34.6% of the variance (r = 0.588, P < 0.000), whereas the extent of bone lesions, the presence of more than 50% plasma cells in the bone marrow, the amount of serum monoclonal protein, functional class, and the Salmon and Durie staging system did not significantly add to the analysis. We conclude that the factors that best predict prognosis are hemoglobin levels, and age at pressentation. Different approaches including more appropriate chemotherapeutic regimes and comprehensive geriatric assessment with improved supportive treatment need to be developed for the geriatric patient with multiple myeloma.

Accelerated Phase of Chronic Myeloid Leukemia Presenting with Hypercalcemia and a Mediastinal Mass

A patient with chronic myeloid leukemia developed hypercalcemia as a presenting sign of the accelerated phase of the disease. Ultrasound of the neck showed a large hypodense mass connected to the thyroid gland, which was thought to be a parathyorid tumor and the cause of the hypercalcemia. Histology of the surgically removed mass revealed a chloroma. The patient’s course was complicated by respiratory failure and metastatic calcinosis of the lung, an unusual finding in hypercalcemia of short duration.

Fulminant Bilateral Cerebellar Syndrome in a Patient with Chronic Lymphocytic Leukemia

A 55 year old patient with chronic lymphocytic leukemia (CLL) and long-standing excessive lymphocytosis developed a rapidly progressive neurological syndrome. Differential diagnosis focused on two rate neurological complications in this disease: direct brain infiltration by leukemic cells versus progressive multifocal leukoencephalopathy (PML). Tissue diagnosis was not available. Two cerebro-spinal fluid examinations performed during the presence of the acute neurological symptoms were normal. Computed tomography (CT) showed low density lesions without enhancement and no mass effect within the left cerebellum. Magnetic resonance imaging scan (MRI) demonstrated multiple hyperintense areas in the brain stem, right and left cerebellum and right capsula interna, suggestive of demyelinative process. In our opinion these findings were compatible with the diagnosis of PML, but biopsy was not performed. Because of the different therapeutic approach in these two conditions, we feel that tissue diagnosis is warranted in patients with CLL who develop a rapidly progressive central nervous system complication in the presence of normal CSF.

Hydroxyurea as a Cause of Drug Fever

We report on a patient with essential thrombocythemia treated with hydroxyurea who became febrile 3 weeks after the treatment was started. After drug withdrawal, the fever resolved but after rechallenge there was recurrence of the fever. Although hydroxyurea-induced fever is rare, this drug must be added to the list of drugs that produce fever and the physicians should be aware of this possibility.

Autonomous growth of committed hematopoietic progenitors from peripheral blood of workers exposed to low levels of benzene.

We investigated whether exposure to low levels of benzene (geometric mean of exposures = 0.28–0.41 parts per million) results in perturbations of the hemopoietic system found in patients with myeloproliferative diseases. Erythroid (BFU-E) and granulocyte–monocyte (CFU-GM) colonies from peripheral blood were grown in methylcellulose with and without the addition of cytokines (erythropoietin and granulocyte-stimulating factor). Colony growth from 17 workers exposed to low levels of benzene was compared with 20 healthy control subjects. Exposed workers had significantly increased growth of autonomous BFU-E and unstimulated CFU-GM when compared with the control subjects. Unexposed smokers had increased colony growth without the addition of cytokines. Colony growth was not significantly different between the groups after the addition of cytokines. Workers exposed to low concentrations of benzene and unexposed smokers have increased cytokine-independent hematopoiesis.

Fatal fludarabine-induced extensive bone marrow necrosis in a patient with chronic lymphocytic leukemia.

To the Editor; Bone marrow necrosis (BMN), rarely diagnosed during life, consists of BM destruction of hematopoietic tissue as well as medullary stroma, but with preservation of the bone. It is commonly found in patients with neoplastic diseases, severe infections, sickle cell anemia and after drug ingestion and the prognosis is generally poor. In chronic lymphocytic leukemia (CLL) BMN is a rare event. Here we report what we feel is the first case of Fludarabine-induced BMN in a patient with CLL. BMN is rarely diagnosed antemortem, but is often seen at necropsy. It is a clinico-pathological entity, of both hematopoietic cell and medullary stroma destruction but with bone preservation [1]. The prognosis in these cases is very poor indeed [2]. This phenomenon has been observed during the course of neoplastic diseases, both hematologic (leukemia, non-Hodgkin’s lymphoma) and solid tumors (including breast, lung, prostate, esophageal, gastric and ovarian) [2]. Fludarabine monophosphate is a purine (nucleoside) analog which is a cytotoxic analog of the normal intracellular metabolite deoxyadenosine monophosphate and is an active anticancer agent, with significant efficacy in chronic lymphocytic leukemia patients [3]. BMN is rarely seen in patients treated with Fludarabine. Here, we report a rare case of fatal BMN after Fludarabine administration in a CLL patient. A 68-year-old woman was diagnosed as having B-CLL (CD5þ/CD19þ/CD23þ/Kappa/FMC72/CD382/CD79b2) stage 0 (Rai), with 12.5 £ 10/l leukocytes, 58% lymphocytes, hemoglobin (Hb) 15 mg/dl, MCV 84 fl, platelets (Plt) 344 £ 10/l, LDH was 368 IU/l, direct Coombs negative; hypogammaglobulinemia of 9.8% (total protein 7.8 g/dl, globulin 1.9 g/dl) was evident. Physical examination was normal as was a CTof the neck, chest, abdomen and pelvis. Six years later there was disease progression with a rapid doubling time of leukocytes (80 £ 10/l); 6 months earlier the number of WBC was 36 £ 10/l. The level of Hb was low (10.9–10.7 mg/dl). Beta2microglobulin (B2MG) levels were high (6623 ng/ml). Cervical and axillary lymph node enlargement as well as enlargement of lymph nodes in the retroperitoneum and splenomegaly were evident in a CT scan. At the same time progressive multifocal leukoencephalopathy was diagnosed by the neurologist, who was convinced that these neurologic clinical features were related to CLL. Two courses of Chlorambucil did not change the situation and Fludarabine was started, 40 mg/m IV, for 5 days. After only one course severe pancytopenia developed: WBC 1.09 £ 10/l (with total polymorphonuclears of 0.45 £ 10), Hb 9.1 mg/dl, MCV 89 fl, Plt 19 £ 10/l. A bone marrow biopsy (BMB) showed no megakaryocytes, few myeloid precursors, a hypoplasia of the erythroid cell lineage. Lymphocytic infiltration and a background of amorphous eosinophilic material was seen, consistent with the diagnosis of BMN (Fig. 1). The CBC worsened and the level of WBC went down to 0.43 £ 10/l, while the Hb dropped to 4.5 mg/dl and the Plt dropped to ,5 £ 10/l. Prednisone treatment, followed by Cyclosporine and later Anti-Thymocyte Globulin, did not improve the clinical status. Due to the severe immunosuppression, infections with E. coli, Enterococcus fecalis, Pseudomonas and Herpes simplex developed. Later aseptic necrosis of the right hip was also diagnosed by a bone scan. Repeated red blood cell and Plt transfusions, G-CSF and adequate antibiotic treatment were administered, without any improvement in her condition. Five months after this single course of Fludarabine, the patient died because of sepsis.