[Sensory ataxic neuromyelopathy in acquired copper deficiency]. / Ataxie proprioceptive et carence en cuivre masquée.

INTRODUCTION: Neurological involvement associated with copper deficiency has been reported recently in humans and may be under-recognized. CASE REPORT: A 65-year-old patient, with past history of gastrectomy 40 years earlier, developed a myelodysplastic syndrome and then subacute onset of progressive gait ataxia and paresthesias in the lower extremities. Serum vitamin B12 level was low but neurological deterioration persisted, despite vitamin replacement therapy and normal cobalamin level. Further diagnostic investigations revealed severe copper deficiency. Copper supplementation led to hematologic improvement and neurological stabilization. CONCLUSION: Copper and vitamin B12 deficiency, due to malabsorption as a cause of progressive neuromyelopathy and hematologic manifestations, may coexist.

Oncolytic activity of vesicular stomatitis virus in primary adult T-cell leukemia.

Treatments for hematological malignancies have improved considerably over the past decade, but the growing therapeutic arsenal has not benefited adult T-cell leukemia (ATL) patients. Oncolytic viruses such as vesicular stomatitis virus (VSV) have recently emerged as a potential treatment of solid tumors and leukemias in vitro and in vivo. In the current study, we investigated the ability of VSV to lyse primary human T-lymphotropic virus type 1 (HTLV-1)-infected T-lymphocytes from patients with ATL. Ex vivo primary ATL cells were permissive for VSV and underwent rapid oncolysis in a time-dependent manner. Importantly, VSV infection showed neither viral replication nor oncolysis in HTLV-1-infected, nonleukemic cells from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and in naive CD4(+) T-lymphocytes from normal individuals or in ex vivo cell samples from patients with chronic lymphocytic leukemia (CLL). Interestingly, activation of primary CD4(+) T-lymphocytes with anti-CD3/CD28 monoclonal antibody, and specifically with anti-CD3, was sufficient to induce limited viral replication and oncolysis. However, at a similar level of T-cell activation, VSV replication was increased fourfold in ATL cells compared to activated CD4(+) T-lymphocytes, emphasizing the concept that VSV targets genetic defects unique to tumor cells to facilitate its replication. In conclusion, our findings provide the first essential information for the development of a VSV-based treatment for ATL.

Incidence of hematological malignancies in Martinique, French West Indies, overrepresentation of multiple myeloma and adult T cell leukemia/lymphoma.

A registry of hematological malignancies is held in the unit of cytology of the University Hospital of Martinique. Human T cell lymphotropic virus type-1 (HTLV1) is endemic in this island. We determined the incidence and epidemiological features of hematological malignancies from the 715 new cases diagnosed between 1990 and 1998 among the adult population. Incidence rates per year were steady during this period. The most frequent hematological malignancies were multiple myeloma (MM) (34%), followed by non-Hodgkin's lymphoma (NHL) (23%). Among the cases of NHL with an immunohistological study, 57% had a T cell phenotype. Among these 61% were adult T cell leukemia/lymphoma. Epidemiological data on hematological malignancies in the West Indies has not been previously reported. There are two striking differences with other population-based registries: a high incidence of MM (5/100000) and a high proportion of T cell NHL among NHL (57%). The high proportion of T cell NHL is probably due to the high incidence of ATL. A low incidence of B cell NHL might also contribute to this effect. The increased incidence of MM in West Indies had not been previously reported. A similar high incidence of MM has been reported among Afro-Americans in the USA.

Effect of Strongyloides stercoralis infection and eosinophilia on age at onset and prognosis of adult T-cell leukemia.

Onset of adult T-cell leukemia (ATL) usually follows a long period of viral latency. Strongyloides stercoralis infection has been considered a cofactor of leukemogenesis. Hypereosinophilia (HE) is also observed and could be associated with either the presence of parasites or the leukemic process. In non-Hodgkin's lymphoma, eosinophilia may or may not affect prognosis. To determine whether infection with S stercoralis and therefore eosinophilia has a significant effect on the development of ATL, we studied two variables in 38 patients: age at onset and median survival rate. Infected (Ss+) patients (n = 19) were younger (P = .0002) and survived longer (P = .0006) than uninfected (Ss-) patients (n = 19) (median age, 39 vs 70 years; median survival, 167 vs 30 days). Mean survival of patients with hypereosinophilia (HE+) was not significantly different from that of patients without hypereosinophilia (HE-) (P = .57). However, overall survival was longer for Ss + HE + patients than for Ss-HE-patients (P = .01; 180 vs 30 days) or Ss-HE + patients (P = .03; 180 vs 45 days). Among patients with mean survival more than 180 days, Ss + HE + patients survived longer (P = .028). Our data confirm that cofactors related to the environment, such as S stercoralis and hypereosinophilia associated with S stercoralis or human T-cell leukemia virus, type 1 (HTLV-1) might be important in HTLV-1-associated leukemogenesis and suggest that hypereosinophilia affects the prognosis of HTLV-1-associated leukemia.

Lack of efficacy of 2-chlorodeoxyadenoside in the treatment of splenic lymphoma with villous lymphocytes.

Splenic lymphoma with villous lymphocytes (SLVL) is a B-cell chronic lymphoproliferative disorder. Splenectomy and/or chlorambucil (CLB) are usually regarded as the most effective treatment in SLVL patients. However, a few patients relapse and the second line therapy remains questionable. Although 2-Cda has been evaluated in patients with chronic lymphoid leukemia (CLL) and hairy cell leukemia (HCL), it has been reported as the treatment of SLVL in only one case report. Therefore, we have evaluated its efficacy and toxicity in 7 SLVL patients. The median duration between diagnosis and treatment was 18 months (range, 1 to 59). The patients received 2-CdA (0.1 mg/kg/d) by venous infusion for 7 days with a median number of 1 cycle (range, 1 to 2) either as a first line therapy (one patient) or after a failure of other therapies (splenectomy, chemotherapy). Two patients achieved a complete response. The first one maintained his CR during a follow-up of 9 months and then relapsed; the second patient remained in CR after a follow-up of 20 months. Four patients achieved a partial response and relapsed after a median follow-up of 3.5 months (range, 1 to 4). One patient had no response. The treatment was not well tolerated with many infectious events. In the limits of our study, 2-Cda does not appear to be efficient therapy for SLVL and is not well tolerated for patients in relapse after splenectomy or resistant to CLB.

Epidemiology of histoplasmosis in the French West Indies (Martinique).

The Caribbean islands are presumed to be an endemic zone for Histoplasma capsulatum infection, but no epidemiological studies have been done in this area. Our purpose was to report the epidemiology of histoplasmosis from 1991 to 1997 in the French West Indies (Martinique). Cases identified from the register of the mycology laboratory were analysed retrospectively. Ten cases (9 male and 1 female) were identified; 8 of the patients were infected with HIV (average T4 lymphocyte count in these 8 patients was 32/mm3). Eight patients had cutaneous involvement. The incidence in AIDS patients was 1.7%. The annual incidence in the general population was 0.34/100,000. Our data showed that histoplasmosis is endemic in Martinique, with an incidence in AIDS patients slightly inferior to that in endemic areas of the USA. The high rate of cutaneous forms (80%) is uncommon.

[Treatment of corticodependent systemic lupus erythematosus with low-dose methotrexate]. / Traitement du lupus érythémateux systémique corticodépendant par le méthotrexate à faibles doses.

The authors report an open prospective study in a group of 16 patients who presented systemic lupus erythematosus with cutaneous and articular symptoms, and who required treatment with a minimum dose of 15 mg per day of prednisone. Methotrexate was given at a dose of 7.5 mg IM per week. Efficacy was demonstrated at the third month with a statistical analysis of four evolution parameters. Improvement was observed in 13 patients out of 16 and permitted the reduction of the amount of prednisone required. Secondary relapse occurred in four cases in spite of an increase in the dose of methotrexate (10 mg per week). Minor side effects were observed in four cases, and methotrexate was discontinued in only two cases. This study suggests that treatment by low doses of methotrexate is beneficial to patients with articular and cutaneous manifestations of corticodependent systemic lupus erythematosus and this therapy could be corticosteroid-sparing.

[Sarcoidosis and leukemia/T-cell lymphoma associated with HTLV-1 virus infection in adults (apropos of a case)]. / Sarcoïdose et leucémie/lymphome T de l'adulte associées au virus HTLV-I (à propos d'une observation).

The HTLV-1 virus causes a disturbance of the immune system, the evaluation of which is often difficult. We report a case of sarcoidosis in a 49 year old woman of Martinique as evidenced by bilateral hilar adenopathy, hypercalcaemia, uveitis and granulomatous lesions on histological examination. Serological was positive for HTLV-1 antibodies. Three years later she developed an adult T-cell leukemia/lymphoma. The relationships between the HTLV-1 retroviral infection and different pathologies observed are discussed.

[Adult T-cell leukemia/lymphoma. Clinical aspects]. / Leucémie/lymphome T de l'adulte. Aspects cliniques.

BACKGROUND DATA: Adult T-cell leukemia/lymphoma (ATL) is a malignant proliferation of activated CD4+ T lymphocytes. The disease is almost exclusively found in patients living in retrovirus HTLV-1 endemic areas. VIROLOGY: In ATL, monoclonal HTLV-1 provirus is integrated into atypical lymphocytes, called clover-leaf lymphocytes. The pathogenic mechanism leading to HTLV-1-induced leukemogenesis remains obscure. The disease generally occurs after a long latency period. FOUR CLINICAL SUBTYPES: The diversity of the clinical presentation has led to the classification of ATL into four subtypes: acute or prototype, lymphoma, chronic, and painless. In the acute form of ATL there is a tumor syndrome associated with paraneoplastic hypercalcemia and a high rate of opportunistic infections due to the immunodepression predominated by cellular immunity. CLINICAL COURSE: Prognosis is poor for the acute and lymphomatous forms with a median survival of 6 and 10 months respectively. Infectious episodes are frequent, often caused by Pneumocystis carinii, and require systematic prophylaxis. Screening for anguilulosis and prophylaxis is also necessary.

[Adult T-cell leukemia/lymphoma. Therapeutic aspects]. / Leucémie/lymphome T de l'adulte. Aspects thérapeutiques.

CONVENTIONAL CHEMOTHERAPY: Complete remission of aggressive ATL (acute or lymphomatous forms) can be achieved in about 40% of the patients with conventional chemotherapy, but early relapse and infectious complications is the rule. For painless and chronic ATL, chemotherapy does not appear to be useful and can aggravate the immunodepression. NEW THERAPEUTIC APPROACHES: Encouraging results have been obtained with a combination regimen using an antiretroviral agent (AZT) and interferon alpha. Response rate has been high with good tolerance. In responders, the survival rate is better than with conventional chemotherapy. PERSPECTIVES: The success of a potentially antiretroviral approach for the treatment of this generally chemoresistant disease suggests that HTLV-1 virus could have a continuous effect on in vivo leukomogenesis.

[Panniculitis induced by MINE chemotherapy]. / Hypodermite secondaire à une chimiothérapie de type MINE.

BACKGROUND: Drug-induced panniculitis are uncommon. We report the second case of panniculitis induced by MINE chemotherapy. CASE REPORT: A 31-year-old woman with relapsed Hodgkin disease was treated with MINE cytostatic regimen. Multiple erythematous and painful nodules of panniculitis developed on her chest, abdomen and thighs fifteen days after the beginning of drug administration with a second flare up after second administration of the same drugs. The eruption cleared slowly after treatment withdrawal. DISCUSSION: To our knowledge, our case is the second reported case of panniculitis induced by MINE chemotherapy. Drug-induced panniculitis is uncommon and usually induced by steroid treatment. Some cases of panniculitis induced by atenolol, potassium bromide, apomorphine, interferon alpha and interleukin 2 have been described. Few cutaneous adverse effects are reported with MINE chemotherapy: rash, erythema and swelling of extremities. A case of inflammatory swelling of thighs with hemorrhagic panniculitis due to this treatment has been described recently.

[Hypercalcemia of T-cell leukemia in adults]. / Les hypercalcémies des leucémies à lymphocytes T de l'adulte.

A retrospective study of 26 adults with acute T-cell leukemia showed that 14 patients (54%) had hypercalcemia at some point of the disease. Hypercalcemia was found at presentation in nine patients and revealed the disease in one. Eight patients had hypercalcemia at the time of death. Serum phosphorus and parathyroid hormone levels were normal. All patients with hypercalcemia tested positive for the HTLV-1 by Elisa and Western blot. Six patients had focalized or diffuse lytic roentgenographic bone lesions. Hypercalcemia in acute T-cell leukemia may involve production of interleukin-1-alpha and parathyroid hormone-related protein by HTLV-1-infected cells.

Adult T-cell leukemia-lymphoma: a clinico-pathologic study of twenty-six patients from Martinique.

Twenty-six cases of adult T-cell leukemia/lymphoma (ATLL) were identified between 1983 and 1991 in Martinique (French West Indies). There were 14 men and 12 women, all of mixed racial descent and born in Martinique. Their ages ranged from 23 to 95 years. The main clinical and laboratory features at initial presentation were peripheral lymphadenopathy (22 cases), hepatomegaly (11 cases), splenomegaly (10 cases), cutaneous lesions (12 cases), hypercalcemia (16 cases), refractory infection by Strongyloides stercoralis (12 cases), and pre-existing autoimmune disorders (4 cases). All patients had absolute lymphocytosis with circulating pleomorphic abnormal lymphocytes. The prognosis was poor, with most patients (20 cases) surviving for less than 6 months. Although the overall clinicopathologic features of ATLL in this series are similar to those described in previous reports, we observed three additional points of interest: a high association with Strongyloides infection, an increased incidence of tropical spastic paresis/HTLV-1 associated myelopathy (TSP/HAM) among the relatives of the patients (5 cases), and the presence of prior collagen vascular diseases.

Lenograstim for the treatment of neutropenia in patients receiving ganciclovir for cytomegalovirus infection: a randomised, placebo-controlled trial in AIDS patients.

This phase IIa, randomised, single-blind, placebo-controlled study was conducted to determine the dose of recombinant human granulocyte colony-stimulating factor (lenograstim) suitable for use in AIDS patients. The study was conducted at 27 European AIDS/HIV centres, and recruited 69 AIDS patients with an initial episode or relapse of cytomegalovirus infection (neurological site excluded) and an absolute neutrophil count (ANC) < or = 1.0 x 10(9)/L upon diagnosis or between days 1 and 12 of ganciclovir (GCV) treatment. The patients were randomised to placebo (n = 14) or one of four lenograstim arms: 150 microg/m2/d (the standard onco-haematology dose, n = 13) or 100 (n = 13), 50 (n = 15), or 25 microg/m2/d (n = 14). In all groups, the planned dose of GCV was 10 mg/kg/d for 21 d. Median ANC at weeks 2 and 3 was significantly higher in each lenograstim group than in the placebo group (p = 0.05). At week 3, median ANC (x 10(9)/L) was 0.7 in the placebo group, compared with 6.0, 7.4, 4.5, and 2.0 in the 150, 100, 50, and 25 microg2/d lenograstim groups, respectively. Median ANC was not significantly different between the 150, 100, and 50 microg/m2/d lenograstim groups at any time point, but significantly higher in the 50 than in the 25 microg/m2/d group at weeks 2 (p = 0.05) and 3 (p = 0.02). Lenograstim was generally well tolerated, leading to no severe adverse events. In conclusion, lenograstim 50 microg/m2/d is suitable for the treatment of ganciclovir-induced neutropenia and is safe. These results should help the physician choose an optimal and cost-efficient regimen for patients with AIDS-related neutropenia when rHuG-CSF support is indicated.

Implication of HTLV-I infection, strongyloidiasis, and P53 overexpression in the development, response to treatment, and evolution of non-Hodgkin's lymphomas in an endemic area (Martinique, French West Indies).

A clinicopathologic study was conducted to assess the implication of HTLV-I infection, Strongyloides stercoralis (Ss) infection, and P53 overexpression in the development, response to treatment, and evolution of non-Hodgkin's lymphoma (NHL) in Martinique, French West Indies. Two groups of patients, with 22 and 41 participants with B-cell and T-cell lymphoma, respectively, were analyzed. HTLV-I antibodies were detected in 24 (59%) patients with T-cell lymphoma of whom 19 (46%) fulfilled diagnostic criteria of adult T-cell leukemia/lymphoma (ATLL). By comparison with other T-cell lymphomas, patients with ATLL were significantly younger (52 versus 63 years; p = .03), had a significantly higher incidence of hypercalcemia (60% versus 0%; p = .0001), a trend for higher incidence of digestive tract localization (21% versus 4%; p = .1) and significantly shorter median survival (6 versus 17 months; p = .03). Similar results were observed when all 24 HTLV-I-infected patients with T-cell lymphoma were compared with the 17 seronegative patients. Strongyloidiasis was diagnosed in 11 of 34 patients tested for Ss infection. All 4 Ss-infected (Ss-positive) ATLL patients treated with combination chemotherapy achieved complete remission (CR) versus only 2 of 7 Ss-negative ATLL patients (p = .04). In addition, survival of Ss-positive patients with ATLL was better than that of the uninfected patients: 27 versus 5 months, p = .04, respectively). P53 expression was assessed by immunohistochemistry on lymph node biopsies from 37 patients including 18 B-cell lymphomas, 14 ATLL, and 5 other T-cell lymphomas. P53 overexpression (P53-positive) was observed in 6 samples that corresponded in all 6 patients with ATLL. All P53-positive ATLL patients had stage IV disease with elevated lactate dehydrogenase (LDH) levels. By comparison with other ATLL patients studied for p53 expression, P53-positive ATLL were characterized by a lower response rate to combination chemotherapy (CR: 0 of 6 versus 4 of 6; p = .04) and a shorter survival (2 versus 9 months, p = .04). Our results suggest that ATLL represents almost 50% of T-cell lymphomas in Martinique; Ss infection during ATLL seems to be linked with a high response rate to chemotherapy and prolonged survival; and P53 overexpression is observed in almost 50% of aggressive ATLL from Martinique and, even in advanced clinical subtypes, is associated with resistance to chemotherapy and short-term survival.