Bekadja Mohamed Amine, Entasoltan Badra, Amani Kamila, Ouldjeriouat Hafida, Osmani Soufi, Bouchama Samira, Charef Leila, Arabi Abdessamed, Brahimi Mohamed, Bouhass Amar Rachid, Yafour Nabil
Tunis Med. 2022;100(11):762-768.
The storage of harvested stem cells, in standard refrigerators at +4°C, is a simple and inexpensive alternative to cryopreservation for most patients living in countries with limited resources. We present the 10 years' experience of our single center from Oran in Algeria using non-cryopreserved stem cells after conditioning with high dose chemotherapy, in a large group of myeloma and lymphoma patients.
From May 2009 to December 2019, autologous stem cell transplantation (ASCT) was carried out in our center, of which 420 with multiple myeloma (MM) and 154 patients with lymphoma. The source of stem cells in all patients consisted of mobilized autologous peripheral blood stem cells (PBSCs). A median of one cytapherisis was performed (range, 1-3) and the products of the aphaeresis were stored in a conventional blood bank refrigerator at +4°C, in 300-mL transfer packs (Baxter Healthcare) composed of impermeable gas, polyvinyl chloride plastic film. The viability of the harvested cells is assessed by flow cytometry using 7'AAD (7 Amino-Actinomycine D) and was determined by a trypan blue dye exclusion test. The chemotherapy conditioning regimen (Mel200, BEAM, CBV, EAM, BeEAM) started once a minimum of 2×106 CD34+cell/kg in MM or 3x106 CD34+cell/kg in lymphoma was obtained.
In MM patients, the median age at ASCT was 54 years (range; 27-73). The median harvested CD34+ cell count was 3,2x106/kg (range; 1, 22 to 13, 22) and the viability in all cases being >90%. All patients had engraftment on the median of day 9 (range; 7 to 24) and platelet transfusion independence on the median of day 13 (range; 9 to 39). There was no graft failure. Transplant related mortality (TRM) at 100 days was 3,5%. The overall response to transplant was 99% (complete remission (CR) =64,5%; very good partial remission (VGPR) =34%, partial remission (PR) =1,5%). The estimated overall survival (OS) at 5 years was 68% and the median post-transplant progression-free survival (PFS) was 47 months. On December 31th 2021, 41% patient relapsed and 28% died after disease progression. 305 (75%) patients are alive and 237 (59%) without disease activity after a median follow-up of 52 months (range; 13 to 149). In lymphoma patients, 98 Hodgkin`s lymphoma (HL) and 56 non-Hodgkin´s lymphoma (NHL), were auto grafted. The median age at ASCT was 28 years (range; 16-55) and 33 years (17-61) respectively. After mobilization a median of 4,25x106/kg (NHL) and 4,14x106/kg (HL) of CD34+ was infused and the median viability of the cells after 7 days of refrigeration (trypan blue exclusion) was 82%. The median time to achieve 0,5 G/L neutrophil or more was 14 days (9-44) and 15 days (11-27) in HL and NHL, median time to achieve 20 G/L platelets or more at a median of 16 days (10-37) and 17 days (15-28) in HL and NHL. The OS at 5 years was 76% and 67% for patients with HL and NHL respectively. Transplant related mortality at 100 days was 5% in HL and 12,5% in NHL.
This study demonstrates the feasibility of intensified therapy followed by autologous non-cryopreserved PBSCs infusion in MM and lymphoma patients. This method of ASCT is cheaper, and may potentially enable the widespread use of ASCT activities in other hematology centers in Algeria and in developing countries.
对于生活在资源有限国家的大多数患者而言,将采集的干细胞储存在+4°C的标准冰箱中,是一种简单且经济的替代冷冻保存的方法。我们介绍了阿尔及利亚奥兰单一中心在10年间,对大量骨髓瘤和淋巴瘤患者采用高剂量化疗预处理后使用非冷冻保存干细胞的经验。
2009年5月至2019年12月,我们中心进行了自体干细胞移植(ASCT),其中420例为多发性骨髓瘤(MM)患者,154例为淋巴瘤患者。所有患者的干细胞来源均为动员后的自体外周血干细胞(PBSCs)。平均进行了1次血细胞分离术(范围为1 - 3次),血细胞分离产物储存在常规血库冰箱中,温度为+4°C,置于由不透气气体、聚氯乙烯塑料薄膜组成的300 mL转移包(百特医疗)中。使用7'AAD(7 - 氨基放线菌素D)通过流式细胞术评估采集细胞的活力,并通过台盼蓝染料排除试验进行测定。一旦在MM患者中获得至少2×10⁶ CD34⁺细胞/kg或在淋巴瘤患者中获得3×10⁶ CD34⁺细胞/kg,即开始化疗预处理方案(Mel200、BEAM、CBV、EAM、BeEAM)。
在MM患者中,ASCT时的中位年龄为54岁(范围27 - 73岁)。采集的CD34⁺细胞计数中位数为3.2×10⁶/kg(范围1.22至13.22),所有病例的活力均>90%。所有患者在第9天(范围7至24天)中位数时实现造血重建,在第13天(范围9至39天)中位数时实现血小板输注独立。无移植失败情况。100天时的移植相关死亡率(TRM)为3.5%。移植后的总体缓解率为99%(完全缓解(CR)=64.5%;非常好的部分缓解(VGPR)=34%,部分缓解(PR)=1.5%)。5年时的估计总生存率(OS)为68%,移植后无进展生存期(PFS)中位数为47个月。到2021年12月31日,有41%的患者复发,28%的患者在疾病进展后死亡。中位随访52个月(范围13至149个月)后,305例(75%)患者存活,237例(59%)患者无疾病活动。在淋巴瘤患者中,98例霍奇金淋巴瘤(HL)和56例非霍奇金淋巴瘤(NHL)接受了自体移植。ASCT时HL患者的中位年龄为28岁(范围16 - 55岁),NHL患者为33岁(17 - 61岁)。动员后,分别输注了中位数为4.25×10⁶/kg(NHL)和4.14×10⁶/kg(HL)的CD34⁺细胞,冷藏7天后细胞的中位活力(台盼蓝排除法)为82%。HL和NHL患者达到0.5 G/L或更高中性粒细胞的中位时间分别为14天(9 - 44天)和15天(11 - 27天),达到20 G/L或更高血小板的中位时间在HL和NHL中分别为16天(10 - 37天)和17天(15 - 28天)。HL和NHL患者5年时的OS分别为76%和67%。HL患者100天时的移植相关死亡率为5%,NHL患者为12.5%。
本研究证明了在MM和淋巴瘤患者中,强化治疗后输注自体非冷冻保存PBSCs的可行性。这种ASCT方法成本更低,可能会使阿尔及利亚其他血液学中心以及发展中国家广泛开展ASCT活动成为可能。