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Nouvelle bibliothèque de thèse

Hematopoietic Recovery using Multi-Cytokine Therapy in 8 Patients Presenting Radiation-Induced Myelosuppression after Radiological Accidents

International audienceTreatment of accidental radiation-induced myelosuppressionis primarily based on supportive care and requiresspecific treatment based on hematopoietic growth factorsinjection or hematopoietic cell transplantation for the mostsevere cases. The cytokines used consisted of pegylatederythropoietin (darbepoetin alfa) 500 IU once per week,pegylated G-CSF (pegfilgrastim) 6 mg 3 2 once, stem cellfactor 20 lg.kg–1 for five days, and romiplostim (TPO analog)10 lg.kg1 once per week, with different combinationsdepending on the accidents. As the stem cell factor did nothave regulatory approval for clinical use in France, theFrench regulatory authorities (ANSM, formerly, AFSSAPS)approved their compassionate use as an investigational drug‘‘on a case-by-case basis’’. According to the evolution andclinical characteristics, each patient’s treatment was adoptedon an individual basis. Daily blood count allows initiating GCSFand SCF delivery when granulocyte ,1,000/mm3, TPOdelivery when platelets ,50,000/mm3, and EPO when Hb,80g/L. The length of each treatment was based on blood cellrecovery criteria. The concept of ‘‘stimulation strategy’’ islinked to each patient’s residual hematopoiesis, which variesamong them, depending on the radiation exposure’s characteristicsand heterogeneity. This paper reports the medicalmanagement of 8 overexposed patients to ionizing radiation.The recovery of bone marrow function after myelosuppressionwas accelerated using growth factors, optimized bymultiple-line combinations. Particularly in the event ofprolonged exposure to ionizing radiation in dose ranges inducing severe myelosuppression (in the order of 5 to 8 Gy),with no indication of hematopoietic stem cell transplantation

Intensive chemotherapy followed by hematopoietic stem-cell rescue for refractory and recurrent primary CNS and intraocular lymphoma: Société Française de Greffe de Moëlle Osseuse-Thérapie Cellulaire.

International audiencePURPOSE: The prognosis of relapsing primary CNS lymphoma (PCNSL) is poor. We report the results of a prospective multicenter trial of intensive chemotherapy followed by autologous hematopoietic stem-cell rescue (IC + HCR) in immunocompetent adult patients with PCNSL or intraocular lymphoma (IOL) after failure of high-dose methotrexate-based treatment. PATIENTS AND METHODS: Salvage treatment consisted of two cycles of high-dose cytarabine and etoposide (CYVE). Intensive chemotherapy combined thiotepa, busulfan, and cyclophosphamide. Forty-three patients (median age, 52 years; range, 23 to 65 years) were included, with relapse (n = 22), refractory disease (n = 17), or a partial response to first-line treatment (n = 4). The response to CYVE was not assessable in three cases because of treatment-related death. Twenty patients (47%) were chemosensitive to CYVE: 15 of them proceeded to IC + HCR. IC + HCR was also administered to 12 patients who did not respond to CYVE. All but one of the 27 patients who underwent IC + HCR entered complete remission. RESULTS: With a median follow-up of 36 months, the median overall survival was 18.3 months in the overall population, and 58.6 months among patients who completed IC + HCR. The respective median progression-free survival (PFS) times after IC + HCR were 11.6 and 41.1 months. The 2-year overall survival probability was 45% in the whole population and 69% among the 27 patients who received IC + HCR. The 2-year PFS probability was 43% among all the patients and 58% in the IC + HCR subpopulation. CONCLUSION: IC + HCR is an effective treatment for refractory and recurrent PCNSL

« Border Crossing Phenomena and the Law: Which Method? »

Available at SSRN: http://ssrn.com/abstract=280554

Prognostic value of high-sensitivity measurable residual disease assessment after front-line chemoimmunotherapy in chronic lymphocytic leukemia

International audienceMeasurable residual disease (MRD) status is widely adopted in clinical trials in patients with chronic lymphocytic leukemia (CLL). Findings from FILO group trials (CLL2007FMP, CLL2007SA, CLL2010FMP) enabled investigation of the prognostic value of high-sensitivity (0.7 × 10-5) MRD assessment using flow cytometry, in blood (N = 401) and bone marrow (N = 339), after fludarabine, cyclophosphamide, and rituximab (FCR)-based chemoimmunotherapy in a homogeneous population with long follow-up (median 49.5 months). Addition of low-level positive MRD < 0.01% to MRD ≥ 0.01% increased the proportion of cases with positive MRD in blood by 39% and in bone marrow by 27%. Compared to low-level positive MRD < 0.01%, undetectable MRD was associated with significantly longer progression-free survival (PFS) when using blood (72.2 versus 42.7 months; hazard ratio 0.40, p = 0.0003), but not when using bone marrow. Upon further stratification, positive blood MRD at any level, compared to undetectable blood MRD, was associated with shorter PFS irrespective of clinical complete or partial remission, and a lower 5-year PFS rate irrespective of IGHV-mutated or -unmutated status (all p < 0.05). In conclusion, high-sensitivity (0.0007%) MRD assessment in blood yielded additional prognostic information beyond the current standard sensitivity (0.01%). Our approach provides a model for future determination of the optimal MRD investigative strategy for any regimen