[A "historical" case of lead poisoning via drinking water: diagnostic and therapeutic issues]. / Un cas "historique" de saturnisme hydrique: difficultés diagnostiques et thérapeutiques.

INTRODUCTION: It is likely that lead poisoning via drinking water is often overlooked because of its supposed rarity and nonspecific early symptoms, which result in delayed management. EXEGESIS: One case of severe lead poisoning via drinking water is reported. The diagnosis was long missed and a particularly long chelating treatment was required. The clinical features included lead colic, a Burton's lead line, anemia, polyneuritis and arterial hypertension. Eighteen courses of calcium EDTA were required to obtain 'biological recovery'. The poisoning was linked to a very long water supply lead pipe and potomania secondary to alcohol withdrawal. CONCLUSION: This case report illustrates how difficult the early recognition of lead poisoning can be, and underlines the need to inquire about a toxic aetiology, particularly via the environment, of otherwise unexplained pathological conditions.

Multicentric phase II study of cisplatin and etoposide in patients with metastatic carcinoma of unknown primary.

The aim of this study was to determine the efficacy and toxicity of combination cisplatin and etoposide chemotherapy in patients with metastatic carcinoma of unknown primary. Patients were treated with cisplatin (100 mg/m2 iv day 1) followed by etoposide (100 mg/m2 iv days 1-3) every 3 weeks for a maximum of 6 cycles. Patients with progressive disease after two or four courses could receive FAC (fluorouracil, doxorubicin, and cyclophosphamide) until progression. Twenty-five patients were entered and were assessable for response and toxicity. Fifteen (60%) patients had adenocarcinomas. Patients received a median of four courses. Toxicity was mainly hematologic including grade III/IV neutropenia. The overall response rate was 32%. There was no complete response, 32% partial responses, 32% stable disease, and 36% disease progression. Median response duration was 4 months (range: 2-5 months). The median overall survival of the 25 patients was 8 months. No objective response could be obtained with FAC, but 33% of patients achieved stabilization of the disease for at least 3 months. This cisplatin-etoposide combination demonstrated some activity against an usually resistant disease.

Late autologous transplantation in chronic myelogenous leukemia with peripheral blood progenitor cells mobilized by G-CSF and interferon-alpha.

In chronic myelogenous leukemia (CML), autologous stem cell transplantation could be a promising new approach for patients with no cytogenetic response after interferon alpha (IFN-alpha) therapy. We report data on 28 CML patients autotransplanted in chronic phase with peripheral blood progenitor cells mobilized with G-CSF (5 microg/kg/day x 5 days) given subcutaneously while continuing IFN-alpha therapy. At mobilization, 23 patients (82%) were in complete hematological remission (CHR), 16 (57%) achieved a minor cytogenetic response (mcr). We obtained, after stimulation, a median of 37.4 x 10(9)/l (6.9-108) white blood cells, 7.2 x 10(8)/kg (2.2-16.6) mononuclear cells, 39 x 10(4)/kg (4.8-403.5) CFU-GM and 4.2 x 10(6)/kg (0-58.6) CD34+ cells. Six patients received GM-CSF after transplantation. All patients engrafted, with no significant influence stemming from the Sokal index score and pretransplantation IFN-alpha therapy duration. The first cytogenetic evaluation after transplantation showed 11 (39%) major cytogenetic response (Mcr), and nine (32%) mcr with no significant correlation between these responses, the Sokal index score, and pretransplantation IFN-alpha therapy duration, although there was a significant impact from GM-CSF administration (P=0.01). After transplantation, 26 patients received IFN-alpha alone or associated with hydroxyurea. The median follow-up was 12 months after transplantation and 57 months after diagnosis. At the time of follow-up, nine patients were in CHR, six remained stable in chronic phase, three presented an mcr and one remained in Mcr. At the last follow-up, 22 patients were alive. We conclude that the results of this strategy are encouraging in poor IFN-alpha responders but that other prospective studies that try to maintain the cytogenetic responses obtained immediately after transplantation are needed.

Fludarabine alone compared to CHVP plus interferon in elderly patients with follicular lymphoma and adverse prognostic parameters: a GELA study. Groupe d'Etudes des Lymphomes de l'Adulte.

BACKGROUND: Fludarabine was associated with a good response and was well tolerated in patients with follicular lymphoma in phase II trials and this treatment may be associated with less adverse events than treatment with CHVP plus interferon in elderly patients. PATIENTS AND METHODS: One hundred thirty-one patients older than 59 years with a follicular lymphoma and poor prognosis were randomized between the association of CHVP (12 cycles in 18 months) plus interferon (5 MU TIW for 18 months) or fludarabine alone (25 mg/m2/d x 5 days for 6 cycles, then 20 mg/m2/day for 6 further cycles for 18 months). Poor prognosis was defined by the presence of a large tumor mass, poor performance status, the presence of B symptoms, above normal LDH level, or > or = 3 mg/l beta-microglobulin level. RESULTS: Patients treated with CHVP plus interferon had a higher response to treatment, a longer time to progression and a longer survival than those treated with fludarabine alone (P < 0.05 for all analyses). With a median follow-up of 29 months, the 2-year failure-free survival was 63% for the CHVP-plus-interferon arm compared to 49% for the fludarabine arm and the two-year survival was 77% and 62%, respectively. This benefit was confirmed in a multivariate analysis including initial prognostic parameters. Fludarabine alone was associated with less neutropenia than CHVP plus interferon. Interferon was decreased or stopped in 39% of the patients because of severe fatigue. CONCLUSIONS: CHVP plus interferon over 18 months was associated with a better outcome, even though the combination of interferon plus chemotherapy was less well tolerated than fludarabine.

Multicenter randomized phase II trial of idarubicin vs mitoxantrone, combined with VP-16 and cytarabine for induction/consolidation therapy, followed by a feasibility study of autologous peripheral blood stem cell transplantation in elderly patients with acute myeloid leukemia.

To compare the antileukemic efficacy of idarubicin and mitoxantrone in elderly patients with acute myeloid leukemia (AML) and to evaluate the feasibility of autologous transplantation using PBSC after consolidation in those with a good performance status, 160 patients (median age 69 years), with AML at diagnosis, 118 of them with de novo AML and 42 with AML secondary to myelodysplastic syndrome or toxic exposure (sAML), received induction treatment with idarubicin, 8 mg/m2/day or mitoxantrone, 7 mg/m2/day, on days 1, 3, and 5, both combined with VP-16, 100 mg/m2/day on days 1 to 3 and cytarabine (araC), 100 mg/m2/day, on days 1 to 7. G-CSF, 5 microg/kg/day, was administered after chemotherapy in patients aged more than 70 years. Patients in complete remission (CR) received one course of consolidation using the same schedule as for induction except the araC administration was shortened to 5 days. Some patients younger than 70 years were then scheduled for autologous stem cell harvest on days 5 to 7 of G-CSF, 5 microg/kg/day, initiated after hematopoietic recovery from consolidation. Autologous transplantation was performed following an additional chemotherapy conditioning. Ninety-five patients (59%) achieved CR, without significant difference between the idarubicin (56% CR) and mitoxantrone (63% CR) group. There was also no significant difference in CR rate between de novo AML (63%) and secondary AML (55%) (P = 0.12). Patients aged < 70 years had 67% CR, while patients aged > or = 70 years had 49% (P = 0.02). There was no significant difference in the duration of aplasia between the two arms. Median time to neutrophil recovery was 22 days in patients who received G-CSF following induction and 27 days in patients who did not (P = 0.006). Severe extrahematologic toxicities of induction did not differ between the two arms and included sepsis (39%), diarrhea (13%), hyperbilirubinemia (8%), hemorrhage (6%) and vomiting (6%). Overall, 14 patients (9%), died from toxicity of induction. First consolidation was administered in 74 patients of whom seven (9%) died from toxicity. Nineteen patients have received transplantation. Median time to recovery of neutrophils > 0.5 x 10(9)/l was 13 days and of platelets > 50 x 10(9)/l 43 days following consolidation. There were two toxic deaths. Median disease-free survival and survival from time of achieving CR of non transplanted patients are 6 and 7 months respectively without difference between the two arms. Fourteen transplanted patients relapsed at a median of 5 months post-transplant. We conclude that this regimen is well tolerated and has a good efficacy to induce CR, without a significant difference in efficacy and toxicity between idarubicin and mitoxantrone. Intensive postinduction, including transplantation, is feasible; however, this procedure did not seem to prevent early relapse in the majority of patients. Neither the high rate of CR nor consolidation nor transplant procedure in a selected group of patients did translate into improved DFS and/or survival.

Long term outcome of patients with hairy cell leukemia treated with pentostatin.

BACKGROUND: With the introduction of new drugs such as interferon-alpha (IFN) and purine analogs, the management of hairy cell leukemia (HCL) patients has changed. However, pentostatin has been found to produce higher complete remission rates than IFN. The current study was undertaken to investigate response and long term follow-up in HCL patients treated with pentostatin. METHODS: Between March 1989 and October 1996, 49 patients with HCL and 1 patient with a HCL variant were treated with pentostatin. Eighteen patients had received no prior therapy, 31 patients had received prior treatment with IFN, and 1 patient had received prior treatment with 2'-chlorodeoxyadenosine (2'CdA) and IFN. All patients except 1 were treated with a dose of 4 mg/m2 every 2 weeks. The median number of cycles was 12. RESULTS: The overall response rate was 96% (48 of 50 patients); 22 patients (44%) achieved a complete response, 18 patients (36%) achieved a good partial response (defined as residual bone marrow infiltration < 5%), 8 patients (16%) achieved a partial response, and 2 patients died. For a median follow-up of 33 months off therapy, there were 5 recurrences between 12-66 months; 3 of these patients were treated further with and responded to 2'CdA and 2 died of disease progression at 12 and 40 months, respectively. In addition, 3 patients died of unrelated causes (1 of very early infection, 1 of toxic death and another of cardiac arrest) comprising an overall death rate of 14% (7 of 50 patients). The overall survival rate was 86% for a median follow-up of 38 months (range, 8-105 months). Major side effects were febrile episodes, herpes zoster, nausea/emesis, and pancytopenia. CONCLUSIONS: This analysis confirms both the high remission rate and durable responses that may be achieved with pentostatin treatment in HCL patients. Although pentostatin is active, the risk of cytopenia and immunosuppression must be evaluated carefully.

Long-term outcome and sequelae in aggressive lymphoma patients treated with the LNH-80 regimen.

One hundred patients with aggressive malignant lymphoma treated with the LNH-80 regimen were evaluated for long-term survival, late relapse and long-term sequelae. The LNH-80 regimen consisted of three intensive courses of adriamycin, cyclophosphamide, vindesine and bleomycin, followed by consolidation and final intensification, as previously described. Of the eighty-four patients who achieved CR after induction, fifty-two are alive in continuous complete remission with a median follow-up of 9.2 years. Twenty-nine CR patients (35%) relapsed. Sixty-six percent of the relapses occurred during the first 18 months following the end of treatment but late relapses were observed up to 7 years off-therapy. The fifty-two long-term responders were evaluated for their ability to resume work, sexual function, fertility and presence of long-term sequelae. Of the 41 patients who worked before diagnosis of their disease, 66% had resumed their normal jobs and 24% had retired. Sexual activity was considered to be satisfactory by 66% of the patients. Eleven of the 15 patients (73%) who wanted children had between one and three children. Seven patients (14%) were considered to have mild long-term sequelae but all long-term survivors reported having an acceptable quality of life. Five of the patients who reached CR (6%) had second neoplasias. The LNH-80 regimen allowed 52% of the patients to benefit from long-term disease-free survival with minor long-term toxicity.

[Prognostic factors, late relapse and outcome of patients with aggressive malignant lymphoma: long term results of LNH-80 protocol]. / Facteurs pronostiques, rechutes tardives et devenir des patients porteurs d'un lymphome malin agressif: résultats à long terme du protocole LNH-80.

The 100 patients with aggressive malignant non Hodgkin lymphoma treated with the LNH-80 regimen were evaluated for long-term survival and quality of life. The LNH-80 regimen consisted of three intensive courses of adriamycin, cyclophosphamide, vindesine and bleomycin, followed by consolidation and final intensification, as previously described. Of the eighty-four patients who achieved CR after induction, fifty-two patients are alive in continuous complete remission with a median follow-up of 9.2 years. Twenty-nine CR patients (35%) relapsed. Sixty-six percent of the relapses occurred during the first 18 months following the end of treatment but late relapses were observed up to 7 years off-therapy. Factors adversely correlated with response in multivariate analysis were poor performance status, bone marrow involvement and the presence of more than one extranodal site. Factors adversely correlated with survival were age, high grade subtypes, and bone marrow involvement. The fifty-two long-term responders were evaluated for quality of life parameters such as working ability, sexual function, fertility and absence of long-term sequelae. Of the 41 patients who worked before disease, 66% had resumed their normal job and 24% had retired. Sexual activity was considered to be satisfactory by 66% of the patients. Eleven of the 15 patients (73%) who wanted children had between one and three children. Seven patients (14%) considered having mild long-term sequelae but all long-term survivors reported having an acceptable quality of life. Five of the patients who reached CR (6%) had a second neoplasia. The LNH-80 regimen allowed 52% of the patients to benefit from long-term disease-free survival with minor long-term toxicity.

[Use of local cobalt therapy in peripheral neuropathies associated with chronic lymphopathies (lymphoses). 2 cases with histo-immunologic and ultrastructural records]. / Intérêt de la cobaltothérapie locale dans les neuropathies périphériques des lymphopathies chroniques (lymphoses). Deux observations avec documents histo-immunologiques et ultrastructuraux.

In two cases of peripheral neuropathy, associated with a chronic lymphopathy, cobalt therapy to the lower limbs provided considerable relief of pain, with partial motor recovery. The disappearance after cobalt therapy of the lymphoid infiltrate of the peripheral nerve leads to discussion of the pathogeni role of this infiltrate. Immunofluorescent and electron microscopic studies form the basis of a discussion of the mechanism of involvement of the peripheral nerve non-secreting lymphopathies (chronic lymphoid leukaemia) and in secreting lymphopathies (Waldenström's disease).

Prognostic value of mouse red cell rosette formation in chronic lymphocytic leukaemia.

Mouse red cell (MRC) rosette formation was studied in 20 malignant haemopathies. Only cells from chronic lymphocytic leukaemia (CLL) and hairy cell leukaemia (HCL) formed MRC rosettes with a high frequency. However, cells from 2 cases of CLL could not be demonstrated to form MRC rosettes, although they were undoubtedly found to be of B origin. These 2 cases presented as typical CLL, but they were observed to transform into a sarcomatous type after 5-6 months of evolution, suggesting that the study of MRC rosette formation might be of prognostic value in CLL.