Bone marrow transplantation prolongs survival after relapse in aggressive-lymphoma patients treated with the LNH-84 regimen.

PURPOSE: Of the 737 patients with aggressive lymphoma who were treated with the LNH-84 regimen, 244 with progressive disease after complete remission or partial response were analyzed retrospectively to determine the influence of intensive chemotherapy with bone marrow transplantation (BMT) on survival. PATIENTS AND METHODS: Forty-four patients were treated with salvage chemotherapy, followed by autologous bone marrow transplantation (ABMT) in 40 and allogeneic BMT in four. The other 200 patients were treated with chemotherapy only. RESULTS: Salvage treatment produced an objective response in 57% of the patients; 23% achieved a second complete remission. Median overall survival was longer for patients who were treated with ABMT than for those who were treated with chemotherapy only (12.4 v 6.7 months), as was median freedom from progression (FFP) survival (7.7 v 4 months). In multiparametric analysis, ABMT and normal initial lactic dehydrogenase (LDH) level were the primary parameters associated with longer survival. This is also true when (1) only patients younger than 60 years of age, (2) only patients who responded to salvage regimen, or (3) only patients with both conditions were included in the analysis. Patients who were not transplanted had a 1.69 to 2.26 relative risk of dying from their disease compared with those who were treated with intensive chemotherapy plus ABMT. CONCLUSION: This study produced more evidence of the favorable impact of intensive chemotherapy with bone marrow rescue on survival in lymphoma patients who had relapsed.

Granulocyte-macrophage colony-stimulating factor in association to timed-sequential chemotherapy with mitoxantrone, etoposide, and cytarabine for refractory acute myelogenous leukemia.

Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), given intravenously 5 micrograms/kg per day, was administered on days 4-8 of timed-sequential chemotherapy (TSC) with mitoxantrone, 12 mg/m2 per day on days 1-3, etoposide, 200 mg/m2 per day on days 8-10 and cytarabine, 500 mg/m2 per day on days 1-3 and 8-10, in 22 patients aged < 60 years with refractory acute myelogenous leukemia in an attempt to increase recruitment of leukemic cells in S phase before the second sequence of TSC. Thirty-eight patients treated with TSC without GM-CSF in a previous trial served as historical controls. In GM-CSF-treated patients, median duration of neutropenia < 0.5 x 10(9)/1 was 33 days and of platelet transfusion requirement 30 days, without any increase by comparison with controls. WHO grade 3 or more extra-hematologic toxicity included sepsis in 60% of patients, vomiting in 30%, diarrhea in 15%, hyper-bilirubinemia in 15%, and mucositis in 10%, without any difference with controls. Among 20 evaluable patients six individuals (30%), with a 95% confidence interval (CI) ranging from 12-54% achieved complete remission, 11 (55%, CI 31-77%) did not respond to therapy and three (15%, CI 3-38%) died from infection. There was no demonstrable in vivo proliferation of leukemic cells during the 5 days of administration of GM-CSF. The average percentage of bone marrow cells in S phase in five patients was 4.0 +/- 2.8 on day 4 and 7.0 +/- 7.2 on day 8 (p = NS). In this cohort of patients refractory to cytarabine, addition of GM-CSF did not increase efficacy of TSC by comparison with historical controls.

Correlation between the biological and therapeutic effects of interferon-alpha in low-grade nodular non-Hodgkin's lymphoma: lack of in vivo down-regulation and reduced affinity of IFN-alpha receptors in unresponsive patients.

We investigated the correlations between the biological effects of interferon-alpha (IFN-alpha) and clinical responsiveness in low-grade non-Hodgkin's lymphomas (NHL). In this disease, 40-50% of cases respond to IFN-alpha therapy. Patients with nodular NHL were selected for a phase II trial in which they were treated daily with 9 x 10(6) U of IFN-alpha 2a. Binding experiments with [125I]IFN-alpha 2a showed the presence of IFN-alpha receptors on tumor B-cells isolated from lymph nodes before therapy in 9 out of 10 patients. Receptor levels were not related to the subsequent clinical responses. However, no specific binding was detected in one patient who turned out to be unresponsive to IFN-alpha treatment. Single injections of IFN-alpha 2a before beginning the therapeutic protocol resulted in down-regulation of IFN-alpha receptors without change in their affinity in peripheral blood leukocytes from only patients who subsequently responded to therapy (4/10). In 4/5 non-responders and one patient displaying a minor response, receptor numbers did not decrease but Kd values rose markedly in all six cases. These results indicate that lack of in vivo IFN-alpha receptor down-regulation and reduced receptor affinity, as detected before therapy, may be correlated with failure of IFN-alpha therapy in nodular NHL.

Allogeneic bone marrow transplantation for postpolycythemic myeloid metaplasia with myelofibrosis: a case report.

Myeloid metaplasia with myelofibrosis develops in about 10% of patients with polycythemia vera. We report a case of a 48-year-old female with postpolycythemic myelofibrosis successfully treated with allogeneic HLA-matched bone marrow transplantation.

[Protective effect of clothing impregnated with permethrin against D. reticulatus and D. marginatus in an open biotope of central western France]. / Effect protecteur de vtements imprégnés de perméthrine vis-à-vis de D. reticulatus et D. marginatus dans un biotope ouvert du centre-ouest de la France.

During the period of major tick activity, in April and May 1998, in the Saint-Maixent l'Ecole area of Poitou, a comparative study was carried out in order to evaluate the protective effect of garments impregnated with permethrin cis/trans 25/75. Three groups of soldiers made up respectively of 208, 218 and 427 men were involved for 2 or 3 days in this experiment. Respectively 107, 107 and 215 wore impregnated uniforms. Out of a total of 319 ticks, 3 were lxodes ricinus, 305 Dermacentor marginatus and 11 D. reticulatus. There was a significant difference in both the intensity (number of ticks per individual, P < 0.0001) and prevalence (number of individuals with ticks, P < 0.001) of ticks on individuals between impregnated and non impregnated uniforms. The repellent effect of permethrin on ticks was observed at the site of preferential tick attachment (normally the head of the host for these two species of Dermacentor in France) where the number of ticks was significantly lower in impregnated uniforms.

[Breast plasmacytoma. Apropos of a case. Review of the literature]. / Le plasmocytome mammaire. A propos d'un cas. Revue de la littérature.

The authors report a new case of a bilateral localisation of a mammary plasmacytoma, as an extension of the multiple myeloma, in a 41-year-old woman. There are 19 cases known. In 2/3 of the cases, the breast localisation was an extension of the multiple myeloma, as the new case reported; the others cases were considered as a solitary plasmacytoma. The authors describe its diagnostic imaging appearance.

[Isolation of viruses in the cerebrospinal fluid in a case of acute varicella meningo-encephalitis]. / Isolement du virus dans le liquide céphalo-rachidien dans un cas de méningo-encéphalite aiguë de la varicelle.

The authors report a case of severe, life-threatening, meningo-encephalitis occurring in a young nonimmunodepressed adult with varicella. The demonstration of a cytopathogenetic effect of his cerebrospinal fluid and of immunoglobulins M specific to the varicella-zoster virus was in favour of an acute, directly viral-dependent encephalitis rather than an immune-mediated leucoencephalitis, as used to be commonly admitted. This is an incitement to use acyclovir in such cases, the effect of which contributes to reinforce this pathogenic hypothesis.

[Adult T-cell leukemia and non-malignant adenopathies associated with HTLV I virus. Apropos of 17 patients born in the Caribbean region and Africa]. / Leucémies à cellules T de l'adulte et adénopathies non malignes associées au virus HTLV I. A propos de 17 malades originaires des Caraïbes et d'Afrique.

Adult T-cell leukaemia is the first blood disease caused by a retrovirus: HTLV-1. The authors report the first French series of 15 patients, of whom 9 came from the classical endemic areas--the Antilles and outer Caribbean Islands--and 6 from Africa where the serological prevalence of HTLV-1 is high but few cases of adult T-cell leukaemia have been reported. Emphasis is laid on the importance of immunodeficiency (refractory strongyloidiasis, Pneumocystis carinii pneumonia, polyclonal B lymphoproliferative syndrome) and of other pathologies associated with the retrovirus (polyarthritis, lymphocytic interstitial pneumonia). The authors also describe the presence of adenopathy in healthy carriers: either adenitis suggestive of retroviral infection, or Castelman's disease adenopathy. These clinical presentations are similar to those described in lymphadenopathy syndromes due to the human immunodeficiency viruses. Aggressive lymphomas require chemotherapy, but sooner or later resistance develops, and the prognosis is very poor. The indications for allogeneic bone marrow transplantation are still to be determined. The diagnosis of adult T-cell leukaemia must be considered in all patients with blood disease coming from the endemic areas.

Evaluation of residual masses after lymphoma treatment: the contribution of gallium 67 tomoscintigraphy.

19 tomoscintigraphies using gallium 67 were performed in 15 patients with Hodgkin's or non-Hodgkin's lymphoma who had a residual mass after treatment. The isotope was never fixed in fibrous masses but was always concentrated in actively growing masses. In five cases histology confirmed these findings. It is recommended that scintigraphy should be considered in every case with a residual mass after treatment, where a decision regarding further treatment is required.

Autologous stem cell transplantation in multiple myeloma: results of the European Group for Bone Marrow Transplantation.

Autologous hematopoietic stem cell transplantation was used for treatment of 384 patients with multiple myeloma in 37 centers during the years 1986-1994. An analysis of prognostic factors was performed in 207 of these patients. One hundred forty one were males and 66 females, and median age was 49 years (range, 24-68). Actuarial survival at 78 months is 45%. Factors associated with a good prognosis were: response on chemotherapy immediately pretransplant, administration of only one treatment regimen, a low serum-beta 2-Microglobulin value at diagnosis and the use of a conditioning regimen including melphalan. In a multivariate analysis, response status pretransplant, age < 45 years, melphalan conditioning and non-TBI conditioning were independently predictive for longer survival, while transplantation after only one line of primary treatment and isotype other than light-chain were of borderline significance. Post-transplant alpha-interferon treatment was associated with improved survival in responsive patients. Eighteen patients treated in one center (Huddinge) passed a double autograft program, and 14 are in continuous complete remission ([CR]; n = 10) or good partial remission (n = 4) at a median time of 17 months after the first transplant (range, 2-38). In five CR patients, polymerase chain reaction (PCR)-analysis of the clone-specific immunoglobulin-rearrangement was performed, and four are PCR-negative up to 33+ months after the first transplantation. We conclude that autografting in myeloma is most effective when applied early in the course of disease in younger, chemotherapy-reponsive patients. Alpha-interferon maintaince treatment seems to be beneficial with respect to improved survival.(ABSTRACT TRUNCATED AT 250 WORDS)

A controlled study of recombinant human granulocyte colony-stimulating factor in elderly patients after treatment for acute myelogenous leukemia. AML Cooperative Study Group.

BACKGROUND: Intensive chemotherapy for acute myelogenous leukemia (AML) continues to yield low rates of complete remission and survival among patients over the age of 65 years. Infection-related mortality is particularly high among these patients during the period of neutropenia that follows chemotherapy. We determined the effect of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) on mortality at eight weeks (the main end point) and the rate of complete remission among patients with AML who were 65 years old or older. METHODS: After induction chemotherapy with daunorubicin (45 mg per square meter of body-surface area per day for 4 days) and cytarabine arabinoside (200 mg per square meter per day for 7 days), 173 patients with newly diagnosed AML were randomly assigned on day 8 to receive either lenograstim (5 micrograms per kilogram of body weight per day) or placebo, starting on day 9, until there was neutrophil recovery or a treatment failure, or for a maximum of 28 days. Salvage chemotherapy was also followed by lenograstim or placebo. Patients with a complete remission received two consolidation courses of chemotherapy without lenograstim or placebo. RESULTS: The mortality rate at eight weeks was similar in the lenograstim and placebo groups (23 and 27 percent, respectively; P = 0.60), as was the incidence of severe infections. The median duration of neutropenia (absolute neutrophil count < or = 1000 per cubic millimeter) was shorter in the lenograstim group (21 days, as compared with 27 days in the placebo group; P < 0.001). Eight percent of the patients in both groups had regrowth of AML cells. The rate of complete remission was significantly higher in the lenograstim group (70 percent, as compared with 47 percent in the placebo group; P = 0.002). Overall survival, however, was similar in the two groups (P = 0.76). CONCLUSIONS: The administration of lenograstim after chemotherapy for AML did not decrease the mortality rate at eight weeks among patients over the age of 65 years. The patients who received lenograstim had a significantly higher rate of complete remission than those who received placebo. Nevertheless, the overall survival in the two groups did not differ significantly.

Successful treatment of adult acute lymphoblastic leukemia after relapse with prednisone, intermediate-dose cytarabine, mitoxantrone, and etoposide (PAME) chemotherapy.

Thirty-nine patients with relapsed acute lymphoblastic leukemia (ALL) and four with primarily refractory ALL were treated with a regimen that included cytarabine 1 gm/m2 (2-hour infusion) twice daily days 1 to 5, mitoxantrone 12mg/m2 daily days 1 to 5, prednisone 0.5 mg/kg daily days 1 to 5, and etoposide 200 mg/m2/day daily days 6 to 8. Of the 43 patients, 30 achieved a complete remission (CR), 28 out of the 39 relapsed patients and two among the four with refractory disease. Five patients died in aplasia. Eight patients were nonresponders. Nonhematologic side effects consisted predominantly of nausea, vomiting, and mucositis. One patient had transient cerebellar dysfunction. Recovery of blood counts occurred at a median of 24 days. The median time to CR was 38 days. As this regimen is highly effective in relapsed or refractory ALL, its use during earlier stage of the disease is warranted.

Prognostic factors of acute non lymphoblastic leukemia in children and adults. Results from two multicentric trials (705 patients).

705 children and adults patients with de novo acute nonlymphoblastic leukemia were entered from 1981 to 1989 into 2 prospectives multicenter trials: 01AM81 and 01AM86. They received an intensive induction course with Rubidazone 200 mg/sqm/day x 4 days and cytosine arabinoside 200 mg/sqm/day x 7 days, then 3 consolidation courses at outpatients, and a maintenance treatment. Total duration of therapy was 3 years. The overall complete remission rate was 80%. The median overall survival time was 19 months and the 5-year survival rate is 26%. The median remission duration for the 568 remitters was 18 months and the 5-year first remission rate is 30%. Prognostic factors for the remission rate were age, initial leukocytosis, FAB subtype. Prognostic factors for remission duration were the delay until CR, initial leukocytosis and karyotype.

Timed sequential chemotherapy for advanced acute myeloid leukemia.

Timed sequential chemotherapy (TSC) combining mitoxantrone on days 1-3, etoposide on days 8-10 and cytarabine on days 1-3 and 8-10, was administered to 240 patients with advanced acute myelogenous leukemia (AML). Sixty one percent of patients, with a 95% confidence interval (CI) ranging from 54 to 67%, achieved complete remission (CR), including 47% (CI: 38-55%) of refractory patients and 78% (CI: 70-86%) of late first relapse patients (p < 0.0001). Thirty percent of patients did not respond to therapy and 9% died from toxicity. Median duration of neutropenia was 32 days and of thrombocytopenia 29 days. Severe non hematologic toxicity included sepsis in 45% of patients and mucositis in 27%. Post-remission therapy varied but included maintenance chemotherapy in most patients, a second course of TSC in 27, autologous stem cell transplantation in 17 and allogeneic transplantation in 20. Median survival of patients who were not transplanted was 7 months with 13% (CI: 7-19%) survival at 5 years. Median disease-free survival (DFS) was 9 months with 13% (CI: 6-20%) DFS at 5 years. Previous refractoriness was the main factor associated with poor prognosis for achieving CR, DFS and survival in a multivariate analysis. There was no difference in DFS between patients receiving the different modalities of intensive post-remission therapy. These results confirm initial reports on TSC and show that some patients with first relapse off therapy can enjoy prolonged DFS using chemotherapy only.