选择性CD34+细胞和非选择性自体外周血干细胞移植治疗多发性骨髓瘤的比较研究

目的明确选择性CD34+细胞自体外周血干细胞移植(APBSCT)治疗多发性骨髓瘤(MM)的临床效果.方法对21例接受CD34+细胞APBSCT治疗的MM患者(选择组)和另外21例接受非选择性APBSCT的MM患者(对照组)的造血恢复时间、有效率、生存率、移植相关不良反应、移植费用进行比较.两组病例在年龄、初诊时血清β2微球蛋白水平和移植时疾病状态均具有可比性,诱导治疗及预处理方案基本相同.结果与对照组相比,选择组患者回输的CD34+细胞数显著偏低[对照组和选择组分别为9.4(1.1～15.0)×106/kg和2.2(0.5～14.3)×106/kg](P＜0.001),中性粒细胞恢复至≥0.5×109/L和血小板恢复至≥20×109/L儿的中位时间,在选择组分别为10d和9d,对照组分别为9.5d(P=0.357)和4.5d(P=0.005).两组的治疗有效率相似(选择组85.7%,对照组90.4%),3年无病生存率(选择组和对照组分别为32%和39%)和总生存率(选择组和对照组分别为85%和79%)两组相比差异无显著性,而且使用非选择性APBSCT可明显降低移植费用.结论选择性CD34+细胞APBSCT与非选择性APBSCT相比,并不能改善MM的临床治疗结果,而且移植费用更大.     

Impact of FAB classification on predicting outcome in acute myeloid leukemia,not otherwise specified,patients undergoing allogeneic stem cell transplantation in CR1: An analysis of 1690 patients from the acute leukemia working party of EBMT

The French, American, and British (FAB) classification system for acute myeloid leukemia (AML) is extensively used and is incorporated into the AML, not otherwise specified (NOS) category in the 2016 WHO edition of myeloid neoplasm classification. While recent data proposes that FAB classification does not provide additional prognostic information for patients for whom NPM1 status is available, it is unknown whether FAB still retains a current prognostic role in predicting outcome of AML patients undergoing allogeneic stem cell transplantation. Using the European Society of Blood and Bone Marrow Transplantation registry we analyzed outcome of 1690 patients transplanted in CR1 to determine if FAB classification provides additional prognostic value. Multivariate analysis revealed that M6/M7 patients had decreased leukemia free survival (hazard ratio (HR) of 1.41, 95% confidence interval (CI), 1.01–1.99; P = .046) in addition to increased nonrelapse mortality (NRM) rates (HR, 1.79; 95% CI, 1.06–3.01; P = .028) compared with other FAB types. In the NPM1^wt AML, NOS cohort, FAB M6/M7 was also associated with increased NRM (HR, 2.17; 95% CI, 1.14–4.16; P = .019). Finally, in FLT3‐ITD⁺ patients, multivariate analyses revealed that specific FAB types were tightly associated with adverse outcome. In conclusion, FAB classification may predict outcome following transplantation in AML, NOS patients.     

Autologous stem cell transplantation in mantle cell lymphoma: a report from the SFGM-TC

Autologous stem cell transplantation (ASCT) is considered as an attractive treatment option for young mantle cell lymphoma (MCL) patients. This retrospective SFGM-TC study analyzed the outcome of 500 MCL patients treated with ASCT and investigated parameters that may modify the outcome of patients who proceeded to ASCT upfront (n?=?396). For all patients, median age at ASCT was 56 years (range, 26–71). Median follow-up was 34 months. Three-year progression free survival (PFS) and overall survival (OS) were 63.5 % [95 % CI, 58.7–68.6 %] and 79.5 % [95 % CI, 75.3–83.4 %], respectively. Median time from ASCT to relapse was 22 months (range, 0–136 m). For patients transplanted upfront and in multivariate analysis, age (HR?=?2 [1.2–3.4], p?=?.01, and HR?=?2.3 [1.2–4.5], p?=?.01), disease status at time of ASCT (HR?=?1.7 [1.1–2.6], p?=?.01 and HR?=?1.8 [1.1–3.1], p?=?.03), and use of rituximab (HR?=?0.5 [0.3–0.8], p?=?.002 and HR?=?0.5 [0.3–0.9], p?=?.01) were statistically predictive for both PFS and OS. Also, first line treatment including anthracycline and high-dose cytarabine followed by ASCT conditioned with TAM improved PFS. To conclude, this study suggests that ASCT in MCL can provide a high response rate but may not be sufficient to cure MCL even when ASCT is performed upfront, highlighting the need for innovative approaches before ASCT, aiming to increase complete response rate, and after ASCT, to maintain response.     

Risk assessment in adult acute lymphoblastic leukaemia before early haemopoietic stem cell transplantation with a geno-identical donor: an easy clinical prognostic score to identify patients who benefit most from allogeneic haemopoietic stem cell transplantation.

In 1402 patients allografted in Europe during the period 1990-2000 with an HLA-identical sibling in first remission (CR1), the median interval from CR1 to allotransplant (96 days) was a major prognostic factor, patients transplanted earlier having a worse outcome. We studied in depth the 414 fully evaluable patients transplanted less than 96 days after achieving CR1; in these patients, only three factors predicted for the outcome by multivariate analysis: patient age, CR1 achievement with one or more induction courses and the recipient/donor sex combination. These three factors overcame the information from cytogenetics and source of stem cells. Three prognostic groups could be identified in relation to the outcome, using a prognostic score affecting 1 to each poor risk factor (total from 0 to 3): Group 1 (good prognosis) includes patients <35 years old, achieving CR1 with one induction course and to be transplanted with any other sex combination than female to male (score 0); group 2 (intermediate) with one adverse factor (score 1); and group 3 (bad prognosis) with two or three adverse criteria (scores 2 and 3). In these three groups, the 3-year leukaemia-free survival was 56+/-5%, 48+/-4% and 29+/-4% and the overall survival was 65+/-5, 53+/-4 and 29+/-5%, respectively. Therefore, adult patients with ALL and a score of 0 or 1 are good candidates for an early transplant if they have an identical sibling donor. Patient age, response to induction and the sex of the HLA-identical family donor (if existing) are the strongest easy predictors of the outcome for an early transplant in an adult patient with ALL. No additional information is mandatory.     

Intensive therapy before or during the conditioning regimen of allogeneic marrow transplantation in adult acute lymphoblastic leukemia patients: we must choose to reduce Toxicity--a Groupe Ouest-Est d'Etude des Leucemies et Autres Maladies du Sang study.

To improve the results in the treatment of adult acute lymphoblastic leukemia patients, different strategies have been proposed. The intensification could concern the induction and early consolidation phases, the conditioning regimen before allogeneic bone marrow transplantation (alloBMT), or both. We analyzed 2 consecutive trials for adult patients in first remission and with the same prognostic features. The Leucemie Aigue Lymphoblastique Paris-Ouest-France (LALPOF) protocol proposed alloBMT with standard conditioning after a classic induction and intensified consolidation scheme; the Groupe Ouest Est des Leucemies Aigues Lymphoblastiques (GOLEAL1) protocol tested an intensified induction and consolidation course before alloBMT with a reinforced conditioning regimen. The 4-year survival rates after alloBMT for LALPOF and GOELAL1 were, respectively, 71% +/- 12% and 36% +/- 13% ( P = .009). The 4-year disease-free survival reached 75% +/- 11% in the LALPOF study and 69% +/- 13% in the GOELAL1 study ( P = .30). The toxic death rate was significantly lower in the LALPOF (2/18) than in the GOELAL1 (6/15) group. Event-free survival at 4 years was significantly higher in LALPOF than in GOELAL1: 66% +/- 11% and 35% +/- 11%, respectively ( P = .02). For adult acute lymphoblastic leukemia patients in first remission, the intensification of chemotherapy before a reinforced conditioning regimen before alloBMT may lead to an increased toxic death rate.     

Reduced Relapse Incidence with FLAMSA–RIC Compared with Busulfan/Fludarabine for Acute Myelogenous Leukemia Patients in First or Second Complete Remission: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Busulfan/fludarabine (BuFlu) is a widely used conditioning regimen for patients with myeloid malignancies. The sequential FLAMSA (fludarabine?+?Ara-C?+?amsacrine chemotherapy) protocol followed by either cyclophosphamide and total body irradiation (FLAMSA-TBI) or cyclophosphamide and busulfan (FLAMSA-Bu) has shown remarkable activity in high-risk acute myelogenous leukemia (AML) patients. Here we compare the outcomes of AML patients transplanted in first complete remission (CR1) or second complete remission (CR2) after conditioning with BuFlu or FLAMSA. Eligible patients had their first allogeneic stem cell transplantation for AML in CR1 or CR2 between January 2005 and June 2016. Donors were matched related or unrelated with up to 1 mismatch. Conditioning consisted of either BuFlu or FLAMSA. Propensity score matching was applied and comparisons were performed using weighted Cox regression. BuFlu conditioning was used in 1197 patients, whereas FLAMSA-TBI and FLAMSA-Bu were used in 258 and 141 patients, respectively. Median follow-up of survivors was 24.72 months. In univariate analysis, relapse incidence (RI) was 30.3%, 21.9%, and 23.1% in the BuFlu, FLAMSA-TBI, and FLAMSA-Bu groups, respectively (P < .01), and nonrelapse mortality at 2 years was 16.1%, 16.4%, and 26.7%, respectively (P < .01). Leukemia-free survival (LFS) at 2 years was 53.6%, 61.6%, and 50.1%, respectively (P = .03). Weighted Cox regression revealed that FLAMSA-TBI compared with BuFlu was associated with lower RI (hazard ratio [HR], .64; 95% confidence interval [CI], .42 to .98; P = .04) and a trend for better LFS (HR, .72; 95% CI, .49 to 1.06; P = .09). These results suggest that compared with BuFlu, conditioning with FLAMSA-TBI leads to reduced RI at 2 years in AML patients transplanted in CR1 or CR2.     

Long-term follow-up after bone marrow transplantation for chronic myelogenous leukemia: factors associated with relapse

Data on 281 patients with chronic myelogenous leukemia who received bone marrow transplants were analysed. The median follow-up time was 40 months; 170 patients were in first chronic phase, 14 were in second chronic phase, 73 were in accelerated phase and 24 were in blastic crisis. The overall actuarial survival was 50% at 5 years. In multivariate analyses, the probability of relapse correlated with the phase of the disease, the method of total body irradiation, the T cell depletion of the marrow and the occurrence of a chronic graft-versus-host disease (GVHD). The probability of survival was better for patients with grade 0-1 GVHD than for patients with grade 2-4 GVHD. In contrast, the probability of disease-free survival was significantly better for patients who received a non-T cell-depleted marrow than for recipients of T cell-depleted marrow. Interval between diagnosis and transplant, splenectomy before transplant, patient age and donor recipient sex match were not significantly associated with outcome. Bone marrow transplantation in first chronic phase with an HLA identical non-T cell depleted marrow offers the better chance of prolonged leukemia-free survival.     

Lesions evoking Sweet's syndrome in acute leukemia: occurring during the stage of therapeutic aplasia

Acute febrile neutrophilic dermatosis, so called Sweet's Syndrome is a distinct dermatological disease defined by constant clinical and histological features: Eruption of painful, tender, raised erythematous plaques of face and neck with fever. Dense dermal infiltration with mature neutrophil polymorphs. Sweet's Syndrome may occur during the course of chronic or acute haematological diseases such as chronic myelogenous leukemia or acute non lymphoblastic leukemia. In all cases, the counts of Neutrophil Polymorphs were normal or above normal limits. We report a case of Sweet's Syndrome occurring during the aplastic period induced by the treatment of an acute myelo monocytic leukemia, and discuss the responsibility of white blood cells transfusion in genesis of typical histological aspect.     

Greffes allogéniques à partir de donneurs non apparentés

In France, nearly half the number of allogeneic stem cell transplants is now from unrelated donors. It is due to this additional source of transplants that the number of patients able to benefit from this potentially curative treatment for several haemopathies has doubled since 1990 (SFGM-TC data, 2007). It is now known how to best select a suitable donor for a given patient, and the efficacy and toxicity of transplants from these donors is known. In brief, the best donor can be selected amongst various options thanks to international collaboration and the efforts of those who created volunteer donor databases.