异基因造血干细胞移植治疗首例自体移植复发霍奇金淋巴瘤的临床分析

目的探讨霍奇金淋巴瘤自体移植复发后行异基因造血干细胞2次移植的可能性和安全性。方法对1例10年前行自体造血干细胞移植复发的霍奇金淋巴瘤患者,行异基因造血干细胞移植,供者为患者母亲,采用外周血干细胞移植,预处理方案采用氟达拉滨+马法兰+兔抗人淋巴细胞免疫球蛋白,预防移植物抗宿主病采用环孢素A、霉酚酸酯、甲氨蝶呤,输注单个核细胞数14.03×108/kg,CD34+细胞6.57×106/kg。结果 2次移植后移植物成功植入,形成完全供者来源造血,移植后第20天骨髓初步植活,造血功能恢复后患者出现皮肤植物抗宿主病,FISH嵌合状态供者细胞植入率为100%,随访至今一直长期无病生存。结论异基因造血干细胞移植,可有效治疗自体移植复发的霍奇金淋巴瘤,是安全有效的挽救治疗措施。     

CD34阳性及阴性成年人急性T淋巴细胞白血病临床分析

目的 分析CD34阳性及阴性成年急性T淋巴细胞白血病(T-ALL)患者的临床特点及预后,探讨CD34表达对T-ALL预后的价值.方法 回顾性分析郑州大学第一附属医院血液科2012年1月至2015年7月收治的75例初治成年T-ALL患者.根据CD34的表达情况,分为CD34阳性组与阴性组,对两组患者的临床特点及预后进行比较.结果 75例初治成年T-ALL患者中,CD34阳性组24例(32.0％),CD34阴性组51例(68.0％).CD34阳性组与阴性组在性别、年龄、肝脾大、淋巴结肿大、血小板减少、白细胞增高、染色体异常、4周完全缓解(CR)率、中枢神经系统白血病(CNSL)方面,差异均无统计学意义(均P＞ 0.05);初诊时CD34阳性组血红蛋白(Hb) ＜90g/L、伴髓系抗原表达者的比例高于阴性组,差异均有统计学意义(x 2=5.888,P=0.015;x 2=10.758,P=0.001).18例选择造血干细胞移植(HSCT),57例未选择HSCT.在未选择HSCT的患者中,CD34阳性组中位生存期为5个月,阴性组为32个月,两者差异有统计学意义(x2=9.172,P=0.002).结论 成年T-ALL患者CD34表达与Hb＜ 90 g/L及髓系抗原表达有关;未选择HSCT患者的CD34表达可能与预后呈负相关.     

The relapse risk of AML patients undergoing autologous transplantation correlates with the stem cell mobilizing potential

Autologous stem cell transplantation (ASCT) is widely used to consolidate first remission in AML. We determined the significance of circulating CD34+ cells at the day of blood stem cell collection in 78 AML patients. Patients mobilizing more than 60,000 CD34+ cells/ml had shorter overall survival (OS; P=0.0274), shorter time to progression (TTP; P=0.0014), and a higher relapse rate (P=0.0177). High levels of CD34+ cells were an independent marker for shorter OS and TTP in a multivariate analysis. These data suggest that ASCT is associated with unfavorable outcome in AML patients with high levels of mobilized peripheral CD34+ cells.     

Lack of benefit of CD34+ cell selected over non-selected peripheral blood stem cell transplantation in multiple myeloma: results of a single center study.

In order to determine the clinical impact of CD34+ cell selected autologous transplantation in multiple myeloma (MM), we have performed a retrospective case-controlled analysis comparing 21 MM patients receiving high-dose melphalan and autologous transplantation with CD34+ peripheral blood stem cells (PBSC) as front-line therapy to 21 control patients receiving unselected products. Case matching was performed using the following criteria: age and beta2-microglobulin at diagnosis and disease status at the time of transplantation. Both cohorts were homogeneous in term of induction treatment and conditioning regimen. Patients were collected for CD34+ selection after priming with G-CSF alone. Significantly fewer CD34+ cells/kg were infused to patients in the selected group as compared to patients in the control group: 2.2 (range 0.5-14.3) vs 9.4 (range 1.1-15) (P < 0.001). The median time to neutrophil recovery > or =0.05 x 10(9)/l was 10 days for the CD34+ group and 9.5 days for the control group (P = 0.357). The median time to platelet recovery > or = 20 x 10(9)/l was 9 days for the CD34+ group and 4.5 days for the control group (P = 0.005). Response rates were comparable in both groups (85.7% in the CD34+ group vs 90.4% in the control group). At 3 years, event-free survival (32% in the CD34+ group vs 39% in the control group) and overall survival (85% in the CD34+ group vs 79% in the control group) were not significantly different. Finally, use of unselected products dramatically reduced the cost of the transplantation procedure. This study shows that CD34+ cell selected autologous transplantation is more expensive than transplantation with unselected products and does not improve the clinical outcome of patients with MM.     

Hematopoietic stem cell transplantation among patients with leukemia of all ages in Texas

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is an effective but expensive medical procedure to which some ethnic minorities, the elderly, and those without insurance have been shown to have limited access. The purpose of the current study was to determine whether socioeconomic factors were associated with HSCT usage rates in patients with leukemia. METHODS: The authors identified 6574 patients with acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, or other leukemias from the 1999 Texas Hospital Inpatient Discharge Public Use Data File. Of these patients, 1604 received an autologous or allogeneic HSCT. The authors assessed patients' ethnicity, payer status, age, gender, and comorbid medical conditions. Logistic regression was used to control for patient characteristics and to evaluate associations among payer status, ethnicity, and HSCT use. P < or = 0.05 indicated statistical significance. RESULTS: Patients who self-paid had the highest rate of HSCT use in all age groups (32%; P < or = 0.01) and in the adult group (36%; P = 0.11). Elderly patients with Medicare had a low rate of HSCT use (17%; P = 0.13). Logistic regression showed no statistically significant associations between payer status or ethnicity and HSCT use. However, elderly women were significantly less likely to undergo HSCT than elderly men (odds ratio, 0.34; P < or = 0.01). CONCLUSIONS: The lack of statistically significant differences in HSCT use among adult patients with leukemia was surprising because previous studies had shown differences in HSCT by ethnicity and insurance.     

Depression, cigarette smoking, and hematopoietic stem cell transplantation outcome

BACKGROUND: The relationships between psychological and behavioral variables and patient outcomes after hematopoietic stem cell transplantation (HSCT) are not known definitively but have great potential importance, since this lifesaving procedure is used increasingly to treat a variety of malignancies. The objective of this study was to evaluate psychosocial predictors of long-term survival and disease recurrence after patients underwent allogeneic HSCT for chronic myelogenous leukemia (CML). METHODS: In this prospective cohort study, 114 adults were admitted for allogeneic HSCT to the Brigham and Women's Hospital between July, 1997 and January, 2002. The median follow-up was 882 days, and serial measures were taken for mood and substance use 6 months and 12 months posttransplantation. RESULTS: With a 93% participation rate by all potentially eligible patients and with < 3% of patients loss to follow-up, univariate predictors of long-term survival and recurrence were identified. Cox proportional hazards regression models for survival and recurrence were developed. Depressive symptoms, as measured by the most recent Beck Depression Inventory (BDI), increased the risk of death by 7% for each point increase in the BDI score (P = 0.006). Fourteen of 17 patients who developed recurrent disease were cigarette smokers with an average of 22.3 pack-years. For each pack-year of cigarette smoking, the risk of recurrence increased by 1.7% (P = 0.01). CONCLUSIONS: This study assessed the role of psychosocial variables prospectively among a clinically homogeneous but representative cohort of patients who underwent allogeneic HSCT. Although additional confirmatory studies are pending, it appears that depressive symptoms posttransplantation and cigarette smoking prior to transplantation affect outcomes adversely and may represent opportunities to improve the morbidity and mortality associated with HSCT for patients with CML.     

自体外周血造血干细胞移植治疗淋巴瘤效果分析

目的:探讨自体外周血造血干细胞移植治疗淋巴瘤的临床效果。方法:回顾性分析2014年1月至2020年12月济宁医学院附属医院行自体外周血造血干细胞移植治疗的41例淋巴瘤患者临床资料,包括霍奇金淋巴瘤6例,非霍奇金淋巴瘤35例。采用化疗药物+粒细胞集落刺激因子（G-CSF）+血小板生成素（TPO）或化疗药物+G-CSF的动员方案。移植前预处理方案：26例患者采用BEAM方案+地西他滨,12例采用BEAM方案,3例采用BEAM方案+西达苯胺。观察患者无进展生存（PFS）及总生存（OS）、相关并发症、移植后转归,以及临床分期、B症状、国际预后指数（IPI）评分、结外累及部位、血红蛋白、乳酸脱氢酶（LDH）、β 2-微球蛋白（β 2-MG）、移植方案、移植前状态对移植后OS及PFS的影响。 结果:41例患者中自体外周血造血干细胞移植前疾病获得完全缓解37例（90.24%）,部分缓解2例（4.88%）,未评估2例（4.88%）。24例干细胞采集资料完整的患者采集的中位有核细胞计数12.74×10 8/kg[（3.91~22.68）×10 8/kg],中位CD34阳性细胞数为6.74×10 6/kg[（0.91~50.47）×10 6/kg]。全部41例患者均获得造血重建,中位血小板植入时间为11 d（7~32 d）,中位粒细胞植入时间为9 d（8~16 d）。41例患者移植后疾病均获得完全缓解,无一例发生移植相关死亡。至随访结束,无疾病进展33例,死亡8例。患者移植后12、24、72个月OS率分别为93.4%、85.3%和60.9%,PFS率分别为93.3%、84.0%、84.0%。中位PFS及OS时间均为未达到。不同性别、临床分期、B症状、IPI评分、结外累及部位、血红蛋白、LDH、β 2-MG、移植前状态患者OS及PFS差异均无统计学意义（均 P>0.05）,移植前预处理方案为BEAM方案+地西他滨患者PFS及OS均优于单用BEAM方案患者（均 P<0.05）。 结论:自体外周血造血干细胞移植治疗淋巴瘤具有较好的效果。BEAM方案+地西他滨预处理方案较单用BEAM方案可获得更长的生存时间。     

Allogeneic hematopoietic stem cell transplantation as part of postremission therapy improves survival for adult patients with high-risk acute lymphoblastic leukemia: a metaanalysis

BACKGROUND: The prognosis for adult patients with acute lymphoblastic leukemia (ALL) remains unsatisfactory primarily because of the high incidence of recurrence. Therefore, optimal postremission therapy is a matter of vital concern. In particular, the clinical efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) should be clarified. METHODS: Rigorous criteria were used to select 7 studies of adult ALL that prospectively assessed overall survival (OS) using natural randomization based on donor availability combined with intention-to-treat analyses. The authors then performed a metaanalysis to evaluate the role of allogeneic HSCT. RESULTS: Seven studies that included 1274 patients were selected. A metaanalysis demonstrated that patients in the donor groups had significantly better survival than patients in the no-donor groups (hazard ratio [HR], 1.29; 95% confidence interval [95% CI], 1.02-1.63 [P = .037]). When only high-risk patients were included in the analysis, the superiority of the survival advantage was even greater (HR, 1.42; 95% CI, 1.06-1.90 [P = .019]). A meta-regression analysis revealed that compliance with allogeneic HSCT showed a significant and positive correlation with survival (coefficient, 0.022; P < .01), suggesting that the greater the proportion of patients who actually received allogeneic HSCT, the better the survival of the donor group. No beneficial effects of autologous HSCT were observed. CONCLUSIONS: The current findings demonstrated that allogeneic HSCT improves the outcome of adult patients with high-risk ALL. Although these analyses were based on abstracted data, the results indicated that allogeneic HSCT should be considered for such patients if a suitable donor is available.     

Similar response rates and superior early progression-free survival with gemcitabine, dexamethasone, and cisplatin salvage therapy compared with carmustine, etoposide, cytarabine, and melphalan salvage therapy prior to autologous stem cell transplantation for recurrent or refractory Hodgkin lymphoma

BACKGROUND: The objective of this study was to compare the response rates, ability to mobilize autologous hematopoietic (peripheral blood) stem cells (PBSCs), and progression-free survival (PFS) after second-line chemotherapy with either gemcitabine, dexamethasone, and cisplatin (GDP) or carmustine, etoposide, cytarabine, and melphalan (mini-BEAM) followed by high-dose therapy and hematopoietic stem cell transplantation (ASCT) for patients with recurrent or refractory Hodgkin lymphoma. METHODS: The outcomes of 68 consecutive patients who were referred for salvage therapy (34 patients received mini-BEAM, and 34 patients received GDP) were compared retrospectively. Patients received mini-BEAM as inpatient treatment every 3-4 weeks, whereas GDP was administered on an outpatient basis every 3 weeks. Responding patients proceeded to stem cell mobilization, followed by high dose etoposide and melphalan, and ASCT. Patients who had disease bulk at recurrence that measured > 5 cm received involved-field radiation post-ASCT. RESULTS: The response rate to GDP prior to ASCT (complete responses, unconfirmed complete responses, and partial responses) was 62% (95% confidence interval [95% CI], 45-78%) compared with 68% (95% CI, 52-83%) for mini-BEAM (P = 0.61). After mobilizing chemotherapy, the proportion of patients for whom the target PBSC number of > or = 5 x 10(6) CD34-positive cells/kg was obtained was 97% after GDP and 57% after MB (P = 0.0003). More patients completed collection with a single apheresis procedure after GDP than after mini-BEAM (73% vs. 36%; P = 0.004), and fewer patients in the GDP group required bone marrow harvesting to proceed to ASCT. After a median follow-up of 1.8 years after ASCT, PFS was significantly better for patients who received GDP compared with patients who received mini-BEAM (74% vs. 35% at 1.5 yrs, respectively; P = 0.005). Overall survival at 1.5 years was 91% after GDP and 82% after mini-BEAM (P = 0.23). CONCLUSIONS: Although this was a retrospective analysis, response to GDP and early PFS after ASCT compared favorably with mini-BEAM salvage chemotherapy. Based on these data, the authors believe that a Phase III trial comparing GDP with mini-BEAM or other platinum-containing regimens is warranted.     

Cytogenetic response to prior treatment with interferon-alpha is predictive for survival after allogeneic hematopoietic stem cell transplantation in chronic myeloid leukemia.

We investigated the impact of a cytogenetic response (CyR) to IFN prior to and at the time of allogeneic hematopoietic stem cell transplantation (HSCT) on transplant-related mortality (TRM), relapse rate and survival probability after HSCT in 162 transplanted patients with chronic myeloid leukemia. One-hundred-one patients (62.3%) achieved a CyR prior to HSCT. Survival probabilities were higher in patients, who achieved any CyR prior to HSCT than in patients without CyR (63.6 vs 49.2%: P = 0.019). Survival probabilities in patients, who achieved a major CyR were better than in patients with minimal and minor CyR or in patients with no CyR (69.4 vs 58.8% vs 49.2%: P = 0.040). TRM and survival of chronic phase patients without CyR at the time of HSCT were similar to that of patients transplanted in advanced phase. Both groups combined had an outcome inferior to patients with at least minimal CyR (TRM, Gray test: P = 0.016, survival, log-rank test: P = 0.002). Univariate and multivariate analyses identified CyR prior to or at HSCT as a strong and independently favorable prognostic factor. We therefore conclude that allogeneic HSCT in CyR should be investigated prospectively as an alternative treatment option in defined patient groups.     

Allogeneic haematopoietic stem cell transplantation for metastatic renal carcinoma in Europe.

BACKGROUND: An allogeneic antitumour effect has been reported for various cancers. We evaluated the experience of allogeneic haematopoietic stem cell transplantation (HSCT) for renal cell carcinoma (RCC) in 124 patients from 21 European centres. PATIENTS AND METHODS: Reduced intensity conditioning and peripheral blood stem cells from an HLA-identical sibling (n = 106), a mismatched related (n = 5), or an unrelated (n = 13) donor were used. Immunosuppression was cyclosporine alone, or combined with methotrexate or mycophenolate mofetil. Donor lymphocyte infusions (DLI) were given to 42 patients. The median follow-up was 15 (range 3-41) months. RESULTS: All but three patients engrafted. The cumulative incidence of moderate to severe, grades II-IV acute GVHD was 40% and for chronic GVHD it was 33%. Transplant-related mortality was 16% at one year. Complete (n = 4) or partial (n = 24) responses, median 150 (range 42-600) days post-transplant, were associated with time from diagnosis to HSCT, mismatched donor and acute GVHD II-IV. Factors associated with survival included chronic GVHD (hazards ratio, HR 4.12, P < 0.001), DLI (HR 3.39, P < 0.001), <3 metastatic sites (HR 2.61, P = 0.002) and a Karnofsky score >70 (HR 2.33, P = 0.03). Patients (n = 17) with chronic GVHD and given DLI had a 2-year survival of 70%. CONCLUSION: Patients with metastatic RCC, less than three metastatic locations and a Karnofsky score >70% can be considered for HSCT. Posttransplant DLI and limited chronic GVHD improved the patient survival.     

The German Hodgkin Study Group risk model is useful for Hodgkin lymphoma patients receiving radiotherapy after autologous stem cell transplant

PurposeTo apply the German Hodgkin Study Group (GHSG) risk model in patients with recurrent/refractory Hodgkin lymphoma receiving involved-field radiotherapy after autologous stem cell transplantation.Material and methodsThe study consisted in the retrospective analysis of 30 consecutive patients with recurrent/refractory Hodgkin lymphoma who received involved-field radiotherapy after autologous stem cell transplantation. Our policy was of adding involved-field radiotherapy for patients with positive PET scan before autologous stem cell transplantation (23 out of 30 patients, 77%), and/or irradiating sites of bulky disease at relapse (11 out of 30 patients, 37%). Patients were stratified into four risk groups according to the presence of the five clinical risk factors identified by the GHSG; (1) stage IV disease; (2) time to relapse ≤ 3 months; (3) ECOG-PS ≥ 1; (4) bulk ≥ 5 cm; and (5) inadequate response to salvage chemotherapy.ResultsThe median interval from autologous stem cell transplantation to involved-field radiotherapy was 3 months (range, 1–7 months), and the median involved-field radiotherapy dose was 35 Gy (range, 12–40 Gy). At a median follow-up of 35 months (range, 1–132 months), the 2-year progression-free survival in the entire series was 60%. When examining the four different GHSG risk groups, the progression-free survival rate at 2 years was 86%, 83%, 50%, and 36% for patients with score = 0, score = 1, score = 2, and score = 3 to 5, respectively (P = 0,01). Among the 12 patients having at least three risk factors who underwent thoracic involved-field radiotherapy, three (25%) developed pneumonitis.ConclusionThe adoption of the GHSG risk model at the time of recurrence/progression is a useful prognostic tool to select patients with Hodgkin lymphoma for consolidative involved-field radiotherapy after autologous stem cell transplantation.     

CD44,CD90的表达与肝癌肝移植术后复发转移的关系

目的:探讨CD44,CD90的表达与肝细胞肝癌肝移植患者预后的关系.方法:收集福州总医院2002至2012年行经典原位肝移植治疗的105例原发性肝细胞癌患者的石蜡包埋标本.应用免疫组化染色法检测肿瘤组织中CD90,CD44的表达,并对临床病理特征及术后随访资料进行统计学分析.结果:CD44和CD90的表达相关关系经Spearman相关分析,两者呈正相关(r=0.5,P＜0.001).COX多因素分析显示,患者5年无复发生存率与CD90高表达(HR=2.765,P=0.002)显著相关.Kaplan-Meier分析显示CD90高表达的患者与CD90低表达患者的肝切除术后5年无复发生存率、术后5年总生存率均有显著差异(40.4％ vs57.6％)(P＜0.05)、(12.7％vs 61.1％) (P＜0.001).COX多因素分析显示,患者5年总生存率与肿瘤大小(HR=1.743;P=0.037)、AFP(HR=2.291;P=0.004)、肿瘤分化(HR=0.283;P＜0.001)、CD44(HR=1.977;P =0.029)、CD90(HR=1.883;P=0.041)表达显著相关.Kaplan-Meier分析显示CD44高表达的患者与CD44低表达患者的肝切除术后5年总生存率有显著差异(16.6％vs 62.7％) (P＜0.001),CD44和CD90共同高表达的患者比CD44或CD90低表达患者的术后5年总生存率显著低(10.7％vs 54.5％)(P ＜0.001).结论:CD90与CD44的高表达相关,CD90与肝癌肝移植术后复发转移有关,二者均影响肝癌肝移植患者预后.     

肥胖对异基因造血干细胞移植效果的影响

目的:探讨肥胖对异基因造血干细胞移植效果的影响。方法:回顾性分析南京医科大学第一附属医院2017年8月至2020年9月行异基因造血干细胞移植的81例患者临床资料。根据体质量指数（BMI）分为肥胖组（BMI≥28 kg/m 2，11例）和非肥胖组（BMI<28 kg/m 2，70例），比较两组患者临床病理特征、造血干细胞植入、移植后并发症、生存及复发等情况。采用Cox比例风险回归模型进行单因素、多因素生存分析。 结果:81例患者中位随访时间280 d（8~1 218 d），1年总生存（OS）率77.9%，1年无进展生存（PFS）率73.8%。非肥胖组与肥胖组1年OS率分别为82.6%和46.2%（ χ2＝15.54， P<0.01），1年PFS率分别为82.1%和36.4%（ χ2＝15.56， P<0.01），非复发死亡（NRM）率分别为7.1%和32.7%（ χ2＝6.463， P＝0.01），累积复发率分别为11.5%和42.9%（ χ2＝8.146， P＝0.004）。非肥胖组和肥胖组中性粒细胞植入时间、血小板植入时间、急性移植物抗宿主病、慢性移植物抗宿主病、出血性膀胱炎、巨细胞病毒感染及EB病毒感染发生情况比较，差异均无统计学意义（均 P>0.05）。多因素分析结果显示，肥胖是异基因造血干细胞移植患者OS的独立不良影响因素（ HR＝3.814，95% CI 1.343~10.827， P＝0.012）。 结论:肥胖是异基因造血干细胞移植后患者生存的重要不良影响因素，改善这部分患者的疗效及生存值得进一步研究探讨。     

大剂量化疗结合自体造血干细胞移植治疗Ⅳ期神经母细胞瘤18例疗效探讨

目的:目前采用常规化疗对Ⅳ期神经母细胞瘤患儿治疗效果欠佳,长期生存率低,本文对采用大剂量化疗结合自体外周血造血干细胞移植及免疫治疗的18例Ⅳ期神经母细胞瘤患儿疗效进行探讨。方法:选择2005年10月～2008年8 月收治的Ⅳ期神经母细胞瘤患儿18例,移植时完全缓解（CR）8 例,部分缓解（PR）6 例,处于肿瘤进展期4 例。年龄1.41~14.33岁,平均6.46±3.25岁,中位年龄6.415 岁。原发部位:后腹膜5 例,肾上腺9 例,胸部3 例,胸腹联合1 例。强烈化疗4~18个疗程,平均9 ± 3.96个疗程,期间进行外周血造血干细胞采集、手术切除,然后进行自体外周血造血干细胞移植,术后行白介素-2 及维甲酸生物治疗,复发者行普通化疗及局部放疗,定期随访。结果:18例患儿自体外周血造血干细胞移植治疗结束后,1 例进展期患儿于移植后5 天因心肺功能衰竭死亡,17例顺利度过移植后骨髓抑制期,造血重建时间为15~19天,平均16.53± 0.91天。术后随访3~34.9 个月,平均15.89±10.37个月,中位随访时间为13.8 个月,完全缓解期8 例获得完全缓解,2 例术后1 年原发灶复发再行普通化疗及局部放疗仍敏感,带瘤生存;部分缓解期3 例获得完全缓解,3 例获得部分缓解,移植后8 个月2 例部分缓解期患儿因颅内转移死亡,1 例部分缓解期患儿带瘤生存;进展期3 例移植重建后稍缓解,分别于移植后3、4、6 个月复发、重要脏器转移死亡。完全缓解期13.8 个月无病生存率75% ;部分缓解期13.8 个月,无病生存率50% ;进展期13.8 个月,生存率为0。3 组自体干细胞移植术后13.8 个月,无病生存率有差别（P<0.05）。 3 组13.8 个月总无病生存率50% ,生存率66.7% 。结论:大剂量化疗、自体外周血造血干细胞移植及白介素-2、维甲酸生物治疗相结合治疗Ⅳ期神经母细胞瘤在移植前达到完全缓解时可取得较好疗效,部分缓解期进行自体干细胞移植可提高缓解率,进展期患儿复发率高,远期治疗效果差。      

IIVP salvage regimen induces high response rates in patients with relapsed lymphoma before autologous stem cell transplantation

Patients with relapsed lymphoma can be cured with high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). New therapeutic approaches with better cytoreductive capacity are needed for relapsed patients to keep their chance for cure with transplantation. We report 30 patients with relapsed lymphoma, median age 43 years, treated with IIVP salvage regimen consisting of ifosfamide, mesna, idarubicin, and etoposide for 2 or 3 cycles. Seventeen patients had non-Hodgkin lymphoma (NHL) and 13 patients had Hodgkin disease (HD). Fourteen (47%) patients were at their first relapse. Overall response rate was 86.6% (n = 26) with 19 patients (63.3%) achieving complete response. Overall response rate was 92% in patients with HD and 82% in NHL. The most frequent side effects observed were grade III-IV neutropenia (87%) and thrombocytopenia (73%). IIVP regimen is a highly effective salvage therapy for patients with relapsed HD or NHL who are candidates for autologous HSCT. Close follow up is necessary because of the high incidence of grade III-IV hematologic toxicity.     

Poor mobilization of peripheral blood stem cells is a risk factor for worse outcome in lymphoma patients undergoing autologous stem cell transplantation

The effect of poor blood stem cells mobilization on the outcome of autologous stem cell transplantation (ASCT) has not been well studied. Our aim is to evaluate poor mobilization as a prognostic factor in lymphoma patients undergoing ASCT. We analyzed 90 consecutive patients with Hodgkin's (HD) and non-Hodgkin's lymphoma (NHL) who underwent ASCT. Poor mobilization was defined as the inability to obtain > or = 1 x 10(6) CD34+ cells/kg ideal body weight with two large volume aphereses. Patients were divided into 2 groups: group 1 = poor mobilizers, and group 2 = good mobilizers. The poor mobilizers received lower median transplant CD34+ cell dose (2 x 10(6) vs. 4.5 x 10(6)/kg for good mobilizers, P = 0.001), were more heavily pretreated (P = 0.01), and required higher number of aphereses for PBSC collection (P = 0.0006). The median progression-free survival (PFS) in groups 1 and 2 was 10 and 41 months (P = 0.04), while the median overall survival (OS) was 38 months and not reached (P = 0.02), respectively. Univariate analysis showed that > or = 3 pre-transplant treatments, CD34+ cell dose < or = 2 x 10(6), elevated LDH before transplant, and poor mobilization were significant prognostic factors for poor PFS, while only the first three were significant for worse OS. Multivariate analysis using these same four factors revealed that number of pre-transplant treatments (HR = 6.03, P = 0.001), CD34+ cell dose (HR = 0.1, P = 0.0007) were the only independent predictive factors for worse overall outcome. In conclusion, our data show that poor mobilization could indicate poor outcome in lymphoma patients undergoing ASCT, however, it is more likely to be a reflection of the heavy pre-transplant therapy and lower CD34+ cell dose re-infused in this group of patients.     

Long-term follow-up of autologous stem cell transplantation in patients with diffuse mantle cell lymphoma in first disease remission: the prognostic value of beta2-microglobulin and the tumor score

BACKGROUND: The current study was conducted to analyze the long-term results of autologous stem cell transplantation (ASCT) in patients with diffuse mantle cell lymphoma (MCL) in first disease remission. METHODS: Thirty-three patients were treated. Thirty-one patients had Ann Arbor Stage III or Stage IV disease. The hyper-CVAD regimen (hyperfractionated intense-dose cyclophosphamide, vincristine, continuous intravenous infusion of doxorubicin, and dexamethasone, alternating with high doses of cytarabine and methotrexate plus leucovorin rescue) was used for cytoreduction before ASCT. Patients were consolidated with high-dose cyclophosphamide (120 mg/kg), total body irradiation, and ASCT. RESULTS: At a median follow-up of 49 months, the overall survival and disease-free-survival rates at 5 years were estimated to be 77% and 43%, respectively. Patients whose M. D. Anderson Lymphoma Tumor Score (TS) was < or = 1 at the time of diagnosis or transplantation experienced longer disease-free survival compared with those whose TS was > 1 (P = 0.02). A beta2-microglobulin (beta2m)level < or = 3 mg/L at the time of diagnosis or transplantation was also found to be strongly predictive of longer survival (5-year survival rate of 100% vs. 22% in patients with a beta2m level > 3 mg/L) (P = 0.0001). CONCLUSIONS: ASCT may prolong the overall survival in a subset of patients with MCL. This improvement has been observed for the most part in patients with low beta2m levels (< or = 3 mg/L) and TS (< or = 1). Randomized trials are required to fully assess the benefits of this strategy.