全反式维甲酸对骨髓纤维细胞的影响

通过纤维细胞集落(CFU-F)的培养,观察了急性早幼粒细胞性白血病(APL)的CFU-F,结果APL 患者较正常骨髓明显低下(4.3±1.63/2×10~5细胞)(n=9);完全缓解后则上升达正常水平(12.4±2.55/2×10~5)。体外试验,维甲酸(RA)加入CFU-F 培养系后,CFU-F 下降为3.11±1.24/2×10~5细胞,明显低于对照组8.5±1.57/2×10~5(P<0.05)。提示RA 对骨髓纤维细胞有抑制作用,此结果可能为RA 治疗骨髓纤维化提供初步依据。     

Disseminated histoplasmosis in a non-immunocompromised host

Histoplasma infections in Europe are rare, and acute disseminated histoplasmosis has only been observed in immunocompromised persons. We describe a case of acute disseminated histoplasmosis in a young, nonimmunocompromised European woman. The probable source of infection was Sri Lanka or the Maldives. At presentation she was severely ill with fever, lymphadenopathy, anemia, thrombocytopenia, hepatosplenomegaly, and polyserositis. Histologically, myelofibrosis and osteosclerosis were observed with extramedullary hematopoiesis. Histoplasma capsulatum yeasts were detected in bone marrow trephine biopsy by methenamine silver staining. Treatment with conventional and liposomal amphotericin B and subsequent itraconazole led to rapid and complete recovery.Abbreviations He Histoplasma capsulatum - AIDS acquired immunodeficiency syndrome - HIV human immunodeficiency virus     

沙利度胺治疗原发性骨髓纤维化临床疗效观察

目的探讨沙利度胺治疗原发性骨髓纤维化(IMF)的临床有效性。方法IMF患者10例,剂量150mg/d,同时羟基脲1.0~3.0mg/d仍维持治疗。根据治疗前后血液学指标白细胞计数、血红蛋白测定、血小板计数和肝脾大小测定的变化及腹胀和下肢浮肿的改善来评定疗效。结果10例脾大患者,9例明显缩小,其中7例巨脾患者5例缩小更显著;2例肝大患者2例恢复正常;5例白细胞升高患者,1例明显降低,2例恢复正常;6例轻中度贫血患者,1例有所上升,2例贫血纠正;4例血小板升高患者,1例明显降低,3例恢复正常。9例腹胀患者,4例好转,3例消失;7例双下肢浮肿患者,2例好转,4例消失。10例IMF患者中,仅2例出现轻度不良反应。结论沙利度胺治疗原发性骨髓纤维化有一定疗效。     

Primary myelofibrosis: risk stratification by IPSS identifies patients with poor clinical outcome

OBJECTIVES:

To evaluate whether risk scores used to classify patients with primary myelofibrosis and JAK-2 V617F mutation status can predict clinical outcome.

METHODS:

A review of clinical and laboratory data from 74 patients with primary myelofibrosis diagnosed between 1992 and 2011. The IPSS and Lille scores were calculated for risk stratification and correlated with overall survival.

RESULTS:

A V617F JAK2 mutation was detected in 32 cases (47%), with no significant correlation with overall survival. The patients were classified according to the scores: Lille - low, 53 (73.%); intermediate, 13 (18%); and high, 5 (7%); and IPSS – low, 15 (26%); intermediate-1, 23 (32%); intermediate-2, 19 (26%); and high, 15 (31%). Those patients presenting a higher risk according to the IPSS (high and intermediate-2) had a significantly shorter overall survival relative to the low risk groups (intermediate-1 and low) (p = 0.02).

CONCLUSIONS:

These results emphasize the importance of the IPSS prognostic score for risk assessment in predicting the clinical outcome of primary myelofibrosis patients.     

Coexistence of Myeloproliferative Neoplasm and Plasma-Cell Dyscrasia

IntroductionPhiladelphia chromosome-negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), and are characterized by clonal proliferation of hematopoietic cells in the bone marrow. There are numerous case reports and reviews reporting patients with coexisting MPN and plasma-cell disease such as multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).MethodsWe report 15 patients treated at our institution over a 5-year period (January 2008 to December 2012) with a diagnosis of both an MPN and MGUS or MM. We also reviewed and summarized published case reports and studies describing the coexistence of these two disease entities.ResultsMost patients (12/15) had an MPN diagnosis made before or at the same time as the MGUS/MM diagnosis. Eventually, 2 patients developed a lymphoid leukemia, 1 patient developed lymphoma, and 1 patient developed acute myeloid leukemia, raising the question of whether patients with coexistence of myeloid- and lymphoid-derived neoplasms are more prone to leukemic or lymphomatous transformation. We did not find any treatment-related effect that could have contributed to the development of coexisting MGUS or MM and MPN. Of the 7 patients with an abnormal karyotype, 3 patients had trisomy 8.ConclusionAt present, management strategies are aimed at treating the MPN and regularly monitoring the MGUS for transformation to an overt plasma-cell malignancy. However, for patients who develop overt MM, management is focused more on treating the myeloma and monitoring the MPN. It has not yet been definitively shown that these 2 entities arise from a common-ancestor hematopoietic stem cell.     

慢性粒细胞白血病80例骨髓活检分析

目的:对慢性粒细胞白血病骨髓活检进行分析,以便全面了解慢性粒细胞白血病的骨髓情况,有助于诊断及治疗。方法:用塑料包埋法制片,然后进行HGF,Gomori染色,观察各项指标。结果:80例病人中78例(97％)骨髓增长明显活跃;19例(61％)伴有不同程度的纤维化;19例(23％)可见3～10个原幼细胞簇。结论:骨髓活检可以全面了解慢性粒细胞白血病的骨髓增生情况、骨髓纤维化程度及原幼细胞簇数量,对判断分期及预后,指导治疗有较重要的意义。     

Family Mismatched Allogeneic Stem Cell Transplantation for Myelofibrosis: Report from the Chronic Malignancies Working Party of European Society for Blood and Marrow Transplantation

This analysis included 56 myelofibrosis (MF) patients transplanted from family mismatched donor between 2009 and 2015 enrolled in the European Society for Blood and Marrow Transplantation database. The median age was 57years (range, 38 to 72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34⁺ cell dose was 4.8?×?10⁶/kg (range, 1.7 to 22.9; n?=?43). Conditioning was predominantly myeloablative in 70% and reduced intensity in the remainder. Regimens were heterogeneous with thiotepa, busulfan, fludarabine, and post-transplant cyclophosphamide used in 59%. The incidence of neutrophil engraftment by 28days was 82% (range, 70% to 93%), at a median of 21days (range, 19 to 23). At 2years the cumulative incidence of primary graft failure was 9% (95% CI 1% to 16%) and secondary graft failure was 13% (95% CI 4% to 22%). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV was 28% (95% CI 16% to 40%) and 9% (95% CI 2% to 17%) at 100days. The cumulative incidence of chronic GVHD at 1 year was 45% (95% CI 32% to 58%), but the cumulative incidence of death without chronic GVHD by 1 year was 20% (95% CI 10% to 31%). With a median follow-up of 32 months, the 1- and 2-year overall survival was 61% (95% CI 48% to 74%) and 56% (95% CI 41% to 70%), respectively. The 1- and 2- year progression-free survival was 58% (95% CI 45% to 71%) and 43% (95% CI 28% to 58%), respectively, with a 2-year cumulative incidence of relapse of 19% (95% CI 7% to 31%). The 2-year nonrelapse mortality was 38% (95% CI 24% to 51%). This retrospective study of MF allo-SCT using family mismatched donors demonstrated feasibility of the approach, timely neutrophil engraftment in over 80% of cases, and acceptable overall and progression-free survival rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimize the risk of graft failure and the relatively high nonrelapse mortality need to be used, ideally in a multicenter prospective fashion.     

慢性粒细胞白血病合并骨髓纤维组织增生44例报道

报道１９７２年～１９９１年中收治４４例慢粒合并骨髓纤维化病人，发病率占同期慢粒收治总数１８３例中的２４％。临床以脾肿大更为突出。病理上髓纤分三度：Ⅰ度骨髓中仅少量纤维组织增生；Ⅱ度骨髓中广泛弥散纤维组织增生；Ⅲ度骨髓广泛纤维组织增生伴骨质增生。慢粒慢性期：Ⅰ度２４例，Ⅱ度１例；加速期：Ⅱ度２例；急变期：Ⅰ度１３例；Ⅱ度４例。认为慢粒合并髓纤预后不一定全部差，视髓纤出现在慢粒分期不同而异。