Granulocyte-macrophage colony-stimulating factor in patients with neutropenic fever is potent after low-risk but not after high-risk neutropenic chemotherapy regimens: results of a randomized phase III trial.

PURPOSE: A randomized unblinded phase III trial was designed to determine the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) to accelerate recovery from febrile neutropenia induced by chemotherapy. PATIENTS AND METHODS: A total of 68 patients with febrile neutropenia following chemotherapy defined as axillary temperature greater than 38 degrees C and absolute neutrophil count (ANC) less than 1 x 10(9)/L were included. After stratification for high- and low-risk chemotherapy to induce febrile neutropenia, treatment was randomized between GM-CSF at 5 microg/kg/d or control, both being associated with antibiotics. RESULTS: GM-CSF significantly reduced the median duration of neutropenia from 6 to 3 days for ANC less than 1 x 10(9)/L(P < .001) and from 4 to 3 days for ANC less than 0.5 x 10(9)/L (P=.024), days of hospitalization required for febrile neutropenia, and duration of antibiotics during hospitalization. The greatest benefit with GM-CSF appeared for patients who had received low-risk chemotherapy, for which the median duration of ANC less than 1 x 10(9)/L was reduced from 7 to 2.5 days (P < .001) and from 4 to 2 days for ANC less than 0.5 x 10(9)/L (P=.0011), the duration of hospitalization during the study from 7 to 4 days (P=.003), and the duration on antibiotics during hospitalization from 7 to 3.5 days (P < .001). A multivariate analysis, using Cox regression, showed that variables predictive for recovery from neutropenia were GM-CSF (P=.0010) and time interval between the first day of chemotherapy and randomization (P=.030). There was no benefit for GM-CSF when high-risk chemotherapy was considered. CONCLUSION: GM-CSF significantly shortened duration of neutropenia, duration of neutropenic fever-related hospitalization, and duration on antibiotics during hospitalization when febrile neutropenia occurred after low-risk chemotherapy, but not high-risk chemotherapy.

Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires. Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: To evaluate prospectively in patients with follicular lymphoma and a low tumor burden three therapeutic options: delay of any treatment until clinically meaningful progression, immediate treatment with an oral alkylating agent, or treatment with a biologic response modifier, interferon alfa-2b. PATIENTS AND METHODS: Newly diagnosed follicular lymphoma patients with a low tumor burden (n = 193) were randomly assigned to one of three arms: arm 1, no initial treatment (n = 66); arm 2, prednimustine 200 mg/m2/d for 5 days per month for 18 months (n = 64); or arm 3, interferon alfa 5 MU/d for 3 months then 5 MU three times per week for 15 months (n = 63). Clinical characteristics were similar in the three arms. RESULTS: Overall response rates with prednimustine and interferon alfa were 78% and 70%, respectively. The overall response to therapy, when deferred, was similar at 70%. With a median follow-up duration of 45 months after randomization, the median freedom-from-treatment (FFT) interval was 24 months in arm 1 and the interval of freedom from treatment failure (FFTF) was 40 months in arm 2 and 35 months in arm 3. The median overall survival time was not reached and the overall survival rate at 5 years was 78% in arm 1, 70% in arm 2, and 84% in arm 3. Therefore, deferred treatment does not adversely influence survival at 5 years. Patients who progressed within 1 year had a significantly shorter survival duration (median, 48 months). CONCLUSION: Delayed treatment is feasible in patients with follicular lymphoma and a low tumor burden. For patients with early progression, more intensive therapy should be considered. For others, because delay of treatment until significant clinical progression does not seem to hamper the prognosis or subsequent response to treatment, the long-term toxicity of alkylating agents can be reduced.

Granulocyte-macrophage colony-stimulating factor accelerates hematopoietic recovery after autologous bone marrow or peripheral blood progenitor cell transplantation and high-dose chemotherapy for lymphoma.

The use of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) as an adjunct to autologous bone marrow transplantation (ABMT) or peripheral blood progenitor cell (PBPC) transplantation was evaluated in 59 lymphoma patients. Patients were divided into three groups. In group I (n = 21) patients received rhGM-CSF (5 micrograms/kg daily) at the time of PBPC collection and during the recovery phase post-infusion. In group II (n = 12) patients received rhGM-CSF as an adjunct to ABMT. In group III (n = 26) they were grafted with bone marrow without rhGM-CSF. Administration of rhGM-CSF (groups I and II) significantly reduced the time to myeloid engraftment, the number of febrile days and the median duration of antibiotics administration and of hospital stay when compared with the group in which patients did not receive rhGM-CSF. The only difference between ABMT and PBPC, given with rhGM-CSF support, was observed in the duration of hospitalization (group I > group II, P < 0.05). These data show that rhGM-CSF is highly effective in reducing the duration of aplasia following BMT and PBPC transfusion, and there appears to be little difference in efficacy between these techniques, provided that patients also receive rhGM-CSF.

[Treatment of metastatic carcinoid tumors with interferon-alpha. Five cases]. / Traitement des tumeurs carcinoïdes métastatiques par interféron alpha. Cinq observations.

OBJECTIVE: Interferon has been proposed in treatment of metastatic carcinoid tumours with varied results. METHOD: Five patients with metastatic carcinoid tumours were treated for 1 year with rIFN alpha 2b at a dose of 5 MU. three times a week during the first month and 10 MU. three times a week during the following months. Carcinoid syndrome was present in all cases. RESULTS: Clinical response with improvement of diarrhoea and flushs was obtained in all cases. Urinary excretion of 5 HIAA and blood serotonin were reduced in 2/5 and 4/5 patients respectively. IFN treatment led to a stabilization of the metastatic tumour in all cases. Recurrence of symptoms was observed within three months following the end of the IFN treatment. CONCLUSION: These findings confirm the contribution of IFN in the treatment of metastatic carcinoid tumours.

[Peripheral T-cell malignant lymphomas. Clinical, morphologic and developmental features in 22 cases]. / Lymphomes malins T périphériques. Aspects cliniques, morphologiques et évolutifs de 22 cas.

Peripheral T-cell lymphomas (PTCL) represent a new subset of malignant lymphomas, which demonstrates a marked morphological, immunological and clinical diversity. They seem to have a worse prognosis globally than B-cell lymphomas. The main clinical characteristics and outcome of PTCL are analysed in this series of 22 cases. The majority of patients had an advanced disease (stages III and IV; 55 percent) and constitutional symptoms (59 percent) at presentation; extranodal localizations were particularly frequent (41 percent). Three patients presented with isolated or predominant spleen enlargement and fever. According to the updated Kiel classification, there were 7 low-grade PTCL and 15 high-grade PTCL. Phenotypic analysis on fresh frozen tissue was available in 16 cases, showing a predominant helper/inducer phenotype (CD4+, CD8-). The complete remission rate was 76 percent for the whole population, but the median of global survival was only 40 months. The few patients who received radiation therapy and subsequently relapsed did not relapse in the irradiated fields, which suggests that radiotherapy might be included in the therapeutic strategy, the best modalities of which remain to be defined.

Human recombinant granulocyte-macrophage colony stimulating factor (hrGM-CSF) improves double hemibody irradiation (DHBI) tolerance in patients with stage III multiple myeloma: a pilot study.

Double hemibody irradiation (DHBI) is an alternative treatment of stage III multiple myeloma (MM) in patients aged over 55 years. Toxic side-effects such as myelosuppression are a severe limiting factor to its use. We performed DHBI associated with human recombinant granulocyte-macrophage colony stimulating factor (hrGM-CSF) as support therapy in 10 patients with stage III MM to improve the tolerance to this treatment. Ten patients received subcutaneously 5 micrograms/kg/d of hrGM-CSF during 2 weeks after each course of hemibody irradiation. All these patients had stage III MM: eight previously received chemotherapy, six of them were regarded as patients with refractory MM and two with relapse. Two patients received DHBI as first-line treatment. hrGM-CSF increased safety and tolerance of DHBI. GM-CSF support reduced the mean time between upper body irradiation (UBI) and lower body irradiation (LBI): 41 v 108 d in a cohort of 32 patients previously treated without growth factor support. Overall there was no lethal infection with hrGM-CSF or granulocytopenia (5.0 x 10(9)/l v 0.4 x 10(9)/l at day 15 in patients without growth factor). hrGM-CSF also reduced stomatitis grading and thrombocytopenia (90 x 10(9)/l v 45 x 10(9)/l at day 15). Furthermore, hrGM-CSF increased blood colony forming unit-granulocyte macrophage (CFU-GM) and was well tolerated in all but one patient. hrGM-CSF reduces toxic side-effects of DHBI, thus providing an effective treatment in patients with advanced and resistant MM.