自体造血干细胞移植治疗鼻腔NK/T细胞淋巴瘤患者长期生存二例

 目的　观察自体外周血造血干细胞移植（APBSCT）治疗结外鼻型NK／T细胞淋巴瘤的长期疗效。方法　回顾分析2例鼻腔NK／T细胞淋巴瘤患者的临床治疗经过及APBSCT 的效果,复习相关文献。结果　2例患者均经鼻腔肿物病理活组织检查确诊,化疗和局部放疗达到完全缓解（CR）,例1接受单次APBSCT,例2接受双次APBSCT。动员方案分别为CNOP方案和CELD方案,预处理方案为卡铂 +阿糖胞苷 +替尼泊苷+地塞米松,移植后造血恢复迅速。定期随访,2例分别无瘤生存60、36个月。结论　化放疗联合APBSCT方案增加了鼻腔NK／T细胞淋巴瘤患者长期生存的机会。     

自体外周血干细胞移植治疗恶性血液病

 目的 观察自体外周血干细胞移植（APBSCT）治疗急性白血病及恶性淋巴瘤的疗效。方法 用APBSCT治疗急性白血病3例,恶性淋巴瘤5例,恶性淋巴瘤采用环磷酰胺联合粒细胞集落刺激因子（G-CSF）动员;3例白血病患者化疗缓解后,予5～9个疗程的化疗巩固治疗,再给予化疗加G-CSF动员。5例恶性淋巴瘤预处理方案为CBV,急性白血病预处理方案为MAC。结果 全部患者均获得完全缓解,随访时间4～12个月,全部病例无病生存,无移植相关死亡。结论 APBSCT是治疗急性白血病及恶性淋巴瘤、改善其预后的主要手段之一,APBSCT后对急性白血病患者应定期进行序贯化疗和免疫治疗,对难治的恶性淋巴瘤患者应进行补救治疗及免疫治疗。     

硼替佐米联合左旋苯丙氨酸氮芥预处理自体干细胞移植治疗多发性骨髓瘤三例

 【摘要】　目的　观察硼替佐米联合左旋苯丙氨酸氮芥为预处理方案进行自体外周血造血干细胞移植（APBSCT）治疗多发性骨髓瘤（MM）患者的疗效及安全性。方法　对3例MM患者诱导治疗缓解后行APBSCT。预处理方案均采用硼替佐米（1.3 mg／m2,－6、－3、+1、+4天）+左旋苯丙氨酸氮芥（200 mg／m2,－2天）。观察治疗后造血重建、并发症及安全性,并进行疗效评价。结果　3例患者移植后造血均快速重建。预处理后不良反应主要表现为恶心、呕吐、乏力、四肢麻木、中性粒细胞及血小板减少等,均经对症治疗后好转。移植后3个月均达完全缓解（CR）,随访期内无复发,患者均无进展生存。结论　采用硼替佐米+左旋苯丙氨酸氮芥预处理进行APBSCT,患者CR率高、无事件生存期长、安全性好,优于传统预处理方案。     

中大剂量阿糖胞苷强化巩固治疗急性髓系白血病15例

 目的　观察中大剂量阿糖胞苷作为急性髓系白血病（AML）缓解后强化治疗方案的临床疗效及其对自体外周造血干细胞采集及造血重建的影响;观察染色体核型分析结果与临床预后的关系。方法　15例AML患者缓解后予中大剂量阿糖胞苷强化治疗;此后有3例患者接受异基因造血干细胞移植（allo-SCT）,7例接受自体外周造血干细胞移植（APBSCT）。结果　2例在CR1期行非血缘allo-SCT,目前均无病生存,1例在复发期行单倍型allo-SCT,在＋110天复发;7例行APBSCT的患者中3例无病生存,另外4例复发;未行移植的5例患者均死亡。7例接受APBSCT的患者采集的中位MNC 7.33×108／kg,中位CD+34细胞6.9×106／kg,中性粒细胞＞0.5×109／L的中位时间＋11天,血小板＞20×109／L的中位时间＋13天。具有预后良好核型的患者3例,2例无病生存;具有预后不良核型的患者4例,2例行allo-SCT,1例行APBSCT,目前均无病生存,另外1例死亡;具有预后中等核型的患者共6例,其中1例联合APBSCT,目前无病生存,其余患者均死亡。结论　中大剂量阿糖胞苷不联合造血干细胞移植作为AML缓解后强化治疗患者复发率较高,具有预后中等和不良染色体核型的患者行allo-SCT可能改善预后;采用中大剂量阿糖胞苷巩固强化治疗的患者均能采集到足够的造血干细胞并能造血重建。     

自体造血干细胞移植治疗预后不良非霍奇金淋巴瘤的临床分析

 目的　观察自体外周血造血干细胞移植（APBSCT）治疗预后不良非霍奇金淋巴瘤（NHL）的疗效和安全性。方法　2003年10月至2008年10月具有预后不良因素的NHL患者10例,经CY+TBI方案预处理（其中2例双次APBSCT患者,第二次给予MEC方案）后行APBSCT治疗。结果　12例次患者均获造血重建,中性粒细胞≥0.5×109／L的时间为7～14 d,中位时间10.58 d,血小板≥20×109／L的时间为10～37 d,中位时间16.25 d。移植后10例患者均完全缓解（CR）,未见严重的不良反应,无移植相关死亡。随访至2009年3月31日,随访时间为3～65个月,中位随访时间为24个月,有7例无瘤生存至今,3例复发,其中1例因疾病进展死亡,另2例经治疗,目前仍带瘤生存。结论　APBSCT是治疗预后不良NHL安全、简便、有效的方法。     

急性髓系白血病自体造血干细胞移植后的维持化疗

 目的　评价急性髓系白血病（AML）自体造血干细胞移植（AHSCT）后维持治疗的疗效。方法　AHSCT治疗AML患者12例,除1例在移植后第20天复发、1例出现再生障碍性贫血外,余10例均在移植后接受标准方案化疗（M3用维甲酸）。结果　12例患者AHSCT后平均生存时间1933（25～4936）d;其中8例患者生存至今,已持续完全缓解91（18～162）个月;5年无病生存率为57.9 ％。结论　应用AHSCT结合移植后维持化疗,可以减少AML复发,延长无病生存期。     

急性髓系白血病自体造血干细胞移植后长期生存并正常生育三例

 目的　探讨造血干细胞移植（HSCT）对患者生育功能的影响。方法　回顾3例接受自体造血干细胞移植（auto-HSCT）后长期生存并正常生育的急性髓系白血病（AML）患者的临床资料,并复习相关文献。结果　3例AML患者中,女1例,男2例,接受不含全身放疗预处理方案的auto-HSCT,分别在停止治疗后68、65和65个月生育一健康小孩。结论　育龄期接受HSCT患者的生育问题在制定治疗方案时应引起重视。     

造血干细胞移植治疗恶性血液疾病及实体瘤的研究

目的 :对 32例造血干细胞移植 (AHSCT)治疗恶性血液病和实体瘤的有关资料进行总结分析。方法 :ABMT组 16例 (NHL 7例 ,HL 6例 ,AML 2例 ,AL L 1例 ) ,13例采用 CBVA方案预处理 ,2例采用 HD- CTX TL I,1例采用 TBI HD- CTX预处理。APBSCT组 16例 (NHL 11例 ,HL 3例 ,MM1例 ,SCL C1例 )用 CTX G- CSF DXM方案动员 ,NHL 采用 CBV方案预处理 ,MM采用 CBM处理 ,SCL C采用 CEP方案处理。结果 :ABMT组 3年、5年生存率在 NHL组为 75 %、75 % ,HL组分别为 10 0 %、83.3 % ;APBSCT组 NHL的 2年、3年生存率为 80 .6 %、6 8.7% ,HL 的 2年、3年生存率均为 10 0 %。 1例 MM、2例 AML、1例 AL L 和 SCL C的存活期分别为 5年、19月、2年和 14月。移植相关死亡率为 0。结论 :造血干细胞移植是治疗恶性血液疾病及实体瘤 ,改善预后的主要手段之一。 ABMT组与 APBSCT组疗效相近 ,患者造血...     

含白消安注射液的预处理方案治疗急性髓细胞白血病二例并文献复习

 目的 评价白消安注射液（ivBu）作为急性髓细胞白血病（AML）造血干细胞移植（HSCT）预处理的疗效和安全性。方法 2例AML患者采用ivBu联合环磷酰胺（Cy）进行预处理,进行HLA相合的同胞外周血干细胞移植,观察其疗效和安全性。结果 2例患者均成功植入,没有严重毒副反应、肝窦状隙阻塞综合征（SOS）、严重急性移植物抗宿主病（GVHD）发生。结论 ivBuCy2方案作为AML预处理方案安全有效。     

自体外周血干细胞移植治疗恶性淋巴瘤的临床研究

目的分析自体外周血造血干细胞移植（APBSCT）治疗恶性淋巴瘤的临床疗效及安全性。方法自1995年12月至2005年12月，采用APBSCT联合大剂量化疗治疗恶性淋巴瘤31例。平均4周期常规诱导化疗后行APBSC动员及采集。动员方案：非霍奇金淋巴瘤（NHL）病人采用常规剂量CHOP方案，霍奇金淋巴瘤（HL）病人采用高剂量单药CTX4g／m^2。预处理方案：异环磷酰胺（IFO）12g／m^2CTX4g／m^2，阿糖胞苷（Ara—C）4．5g/m^2，足叶乙甙（Vp-16）0．75g／m^2。移植后对原发灶直径大于4cm或有肿瘤残留的病灶给予局部补量放疗。结果31例病人移植后缓解时间为1N108mo，中位缓解期43mo。其中1年无病生存26例（83．9％），2年23例（74．1％），3年21例（67．7％）。全组无移植相关死亡。结论APBSCT联合大剂量化疗治疗恶性淋巴瘤的疗效明显优于常规化疗且安全性高值得推广。     

Bone marrow transplantation in hemopoietic malignancies

Several developments have improved disease-free survival after allogeneic bone marrow transplantation. They have mainly involved prophylactic and therapeutic interventions to reduce some of the transplant-related complications. It is now apparent that disease control is achieved by several mechanisms, including the preparative regimen as well as immunologic interactions between tumor cells and cells that are graft derived and belong to the immune surveillance system. Appropriate manipulations of the latter group of mechanisms may result in a better understanding of disease control and make the underlying therapeutic principle universally applicable. Chronic myeloid leukemia patients in the chronic phase appear to have the most optimal risk-to-benefit ratio of all patients transplanted for hemopoietic malignancies. More recent results in acute myeloid leukemia patients transplanted in first remission, however, suggested that allogeneic bone marrow transplantation might also be acknowledged as the treatment of choice in this disease. This conclusion cannot be drawn as yet for patients with acute lymphoblastic leukemia, chronic lymphocytic leukemia, and malignant lymphoma.     

Gemtuzumab ozogamicin as part of reduced-intensity conditioning for allogeneic hematopoietic cell transplantation in patients with relapsed acute myeloid leukemia

PURPOSE: Gemtuzumab ozogamicin (GO) has been associated with an increased risk of liver sinusoidal obstruction syndrome (SOS) when applied within 3 months of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that GO might be safe and effective as part of a reduced-intensity conditioning regimen as salvage therapy of CD33+ acute myeloid leukemia. EXPERIMENTAL DESIGN: Thirty-one patients with acute myeloid leukemia which relapsed following conventional therapy (n=15), autologous (n=3), or allogeneic (n=13) HCT were included in a prospective phase I/II trial. The preparative regimen contained 6 and 3 mg/m(2) of GO on days -21 and -14 before transplantation, leading to a reduction of marrow blasts in 18 patients (58%). Eight patients received further cytoreductive chemotherapy before conditioning therapy was initiated. Fludarabine-based reduced-intensity (n=11) or nonmyelablative (n=16) conditioning and peripheral blood stem cell infusion from related (n=6) or unrelated (n=21) donors could be done in 27 patients during cytopenia. RESULTS: Primary engraftment occurred in all evaluable patients. Only one case of reversible hepatic sinusoidal obstruction syndrome was documented. Non-relapse mortality until day 100 was 22% (n=6). The probabilities of overall and disease-free survival at 24 months were 39% and 35%, respectively. Relapse of leukemia occurring between 2 and 24 months after transplantation (median, 8 months) was the major reason for treatment failure and death. CONCLUSION: These data suggest that GO can be combined with reduced-intensity conditioning even after previous autologous or allogeneic HCT.     

Acute Myeloid Leukemia with Translocation (8;21). Cytomorphology, Dysplasia and Prognostic Factors in 41 Cases

The translocation t(8;21) is one of the most common structural aberrations in acute myeloid leukemia (AML). Excellent response rates and a better relapse-free survival have been described. We analyzed specific morphologic and cytochemical features including dysplasia and other prognostic factors in 41 patients with AML and t(8;21) who underwent aggressive chemotherapy in two national cooperative group studies. Five patients were classified as AML M1 and 36 as AML M2 according to the FAB criteria. Auer rods were detected in 28 patients (68%), however in only 16 patients were they “thin and elongated” as has been described as typical for t(8;21). The presence or absence of Auer rods did not appear to be associated with disease-free survival in this sample. Dysgranulopoiesis was detected in 31/41 patients (90%); five of these patients additionally had dyserythropoiesis (12%). In six cases (15%), dysmegakaryopoiesis was seen in combination with dysgranulopoiesis. Only one patient had trilineage dysplasia. Dysplastic features had no influence on prognosis. Additional cytogenetic abnormalities were detected in 24/41 patients. Twelve male (48%) and four female (25%) had a loss of a sex chromosome. This was correlated with a better disease-free survival (p = 0.039). The complete remission rate (CR) to chemotherapy was 90%. The early death rate was 10%. Disease-free survival of the complete responders was 60% at two years with no relapses observed in ten patients with 2-6 years of follow up. This favorable disease-free survival was observed with a variety of post-induction regimens and t(8;21) had been detected as an independent factor for good prognosis. The need for very intensive therapy, such as bone marrow transplantation, is unanswered at this time.     

Chk1表达与急性髓系白血病细胞多药耐药的关系及临床意义

目的通过检测急性髓系白血病（acute myeloid leukemia,AML）患者的骨髓中单个核细胞上细胞周期检测点激酶1（checkpoint kinase 1,Chk1）的表达,探讨Chk1表达水平与急性髓系白血病临床疗效及预后的关系。方法分析48例急性髓系白血病患者,按临床疗效将其分为完全缓解组和难治耐药组,应用RT-PCR和Western-blot分别检测Chk1 mRNA、蛋白质及磷酸化水平的表达,比较两组间及各组治疗前后Chk1表达水平的差异及其与AML缓解率、复发、无瘤生存期和总生存期的关系。结果 Chk1mRNA及蛋白表达水平在完全缓解组和难治耐药组组间及治疗前后差异无统计学意义（P〉0.05）;Chk1磷酸化（P-Chk1）水平在难治耐药组治疗前后分别为1.17±1.32、2.27±0.98,完全缓解组为0.81±0.62、1.07±0.96,治疗前两组间P-Chk1水平的表达差异无统计学意义（P〉0.05）,治疗后,难治耐药组明显高于完全缓解组,差异有统计学意义（P〈0.05）,且难治耐药组治疗后P-Chk1水平明显高于治疗前,差异有统计学意义（P〈0.05）,完全缓解组治疗前后差异无统计学意义（P〉0.05）;本研究以治疗后P-Chk1/β-actin的比值≥1.0定为P-Chk1阳性表达,根据此标准,难治耐药组P-Chk1阳性表达率为70.6%,显著高于完全缓解组19.4%（P〈0.05）。P-Chk1阳性患者的完全缓解率为37.5%,与P-Chk1阴性患者（78.12%）相比,差异有统计学意义（P〈0.05）;P-Chk1阳性患者复发率高、无瘤生存期和总生存期均短于阴性患者,差异有统计学意义（P〈0.05）。结论 DNA损伤后P-Chk1水平的升高影响了AML细胞对药物的敏感性,P-Chk1阳性表达与AML低解率、高复发率、短的无瘤生存期及总体生存期密切相关,提示Chk1的活化状态参与调控白血病细胞耐药的形成,故推测P-Chk1水平可作为判断急性髓系白血病临床疗效及预后的指标之一。     

难治性白血病诊治进展

 难治性白血病因其本身特性难达完全缓解和长期无病生存,始终是恶性血液病领域研究的热点和难点,国内外关于难治性白血病的诊断标准在不断调整,引起白血病难治高危的因素也在不断的被发现;新的分子标志,基因突变或某些基因高表达,如FLT3 跨膜区内部串联重复等,这些分子标志将决定急性白血病患者的预后。治疗难治性或复发性急性髓细胞性白血病仍然具有挑战性。多种新药正在开发和临床试验。临床许多新的治疗方法正在探讨。如应用耐药逆转剂、加强分子靶向治疗、改进造血干细胞移植和开发新药、组成新的化疗方案等;单克隆抗体和多肽疫苗与白血病相关抗原为治愈急性白血病带来了希望。     

单倍型供者淋巴细胞输注治疗复发性急性白血病

 目的　探讨难治性复发性急性白血病单倍型淋巴细胞输注的疗效。方法　2006年4月至2007年10月应用单倍型淋巴细胞输注治疗复发性急性髓性白血病（AML）3例（M2 2 例,M4 1例）,复发性急性淋巴细胞白血病（ALL）1例,4例复发患者在二线方案化疗无效后,采集供者淋巴细胞,子女供父母3例,母供子1例,供者淋巴细胞在输注前,患者再次接受了不同方案的化疗,白细胞较低时输注供者的淋巴细胞,平均输注细胞2.3（1.4～3.1）×108／kg,输注前淋巴细胞接受了6～8 Gy 60Coγ射线照射。结果　3例AML患者1例获得了完全缓解（CR）,2例有效,1例ALL无效。4例患者输注单倍型供者淋巴细胞后无移植物抗宿主病的发生,未出现严重的骨髓抑制,1例患者发生了带状疱疹病毒感染。结论　单倍型供者淋巴细胞输注配合化疗对难治复发的AML有疗效,输注细胞的数量及照射的剂量需进一步探讨。     

Ablative allogeneic hematopoietic cell transplantation in adults 60 years of age and older.

PURPOSE: To evaluate outcomes of ablative allogeneic hematopoietic cell transplantation (HCT) in older patients with hematologic malignancies. PATIENTS AND METHODS: We treated 52 patients from 1979 to 2002 with a median age of 62.8 years (range, 60.1 to 67.8 years) using ablative preparative regimens followed by allogeneic HCT from sibling donors. Diagnoses included myelodysplastic syndrome (MDS; n = 35), chronic myeloid leukemia (CML; n = 8), acute myeloid leukemia (AML; n = 6), and other (n = 3). Conditioning regimens included cyclophosphamide (CY) and busulfan (BU) (67%), total-body irradiation and CY (21%), BU-fludarabine (10%), and CY (2%). RESULTS: Eighteen (35%) of 52 patients are alive at a median of 4.6 years (range, 0.8 to 9.1 years) after transplantation. Median overall survival (OS) and progression-free survival were 300 and 218 days, respectively. Three-year OS and relapse rates are estimated to be 34% and 24%, respectively. Nonrelapse mortality (NRM) rates at 100 days and 3 years are estimated to be 27% and 43%, respectively. Grade 3 to 4 acute graft-versus-host disease (GVHD) occurred in 20% of patients, and chronic extensive GVHD was described in 53% of patients. Fourteen (40%) of 35 patients with MDS are alive at a median of 2.8 years (range, 0.8 to 8.2 years). Four of six patients with CML in chronic or accelerated phase are alive at a median of 6.9 years (range, 4.1 to 9.1 years) after transplantation. None of the patients with AML, CML in blast crisis, or other diagnoses have survived. Patients who underwent transplantation after 1993 had improved survival. CONCLUSION: These data suggest that allogeneic HCT is feasible in selected patients > or = 60 years of age, although novel methods to reduce NRM while maintaining efficacy are needed.     

自体外周血造血干细胞移植治疗难治性恶性淋巴瘤的临床疗效

目的：探讨自体外周血造血干细胞移植（APBSCT）治疗难治性恶性淋巴瘤的临床疗效。方法：APBSCT治疗难治性恶性淋巴瘤26例,采用CHOP方案化疗加G-CSF动员外周血造血干细胞。结果：26例患者中25例获造血重建,16例获CR（61.53%）,9例PR（34.61%）,1例死于肝静脉闭塞,移植组3年无病生存率达41.70%。结论：对APBSCT治疗难治性恶性淋巴瘤具有较好疗效。明显优于常规化疗。     

Hematopoietic stem-cell transplantation for treatment-related leukemia or myelodysplasia.

PURPOSE: This report describes results of related or unrelated hematopoietic stem-cell transplants in 111 patients with treatment-related leukemia or myelodysplasia performed consecutively at the Fred Hutchinson Cancer Research Center between December 1971 and June 1998, and identifies patient and treatment characteristics associated with survival and relapse. PATIENTS AND METHODS: At transplantation, 56 patients had treatment-related secondary acute myeloid leukemia (AML), 15 had refractory anemia with excess blasts in transition (RAEB-T), 23 had refractory anemia with excess blasts (RAEB), 15 had refractory anemia (RA), and two had refractory anemia with ringed sideroblasts (RARS). Conditioning regimens were total-body irradiation (TBI) and chemotherapy for 60 patients, busulfan (BU) 14 to 16 mg/kg and cyclophosphamide (CY) 120 mg/kg (BUCY) for 27 patients, BU targeted to 600 to 900 ng/mL plasma steady-state concentration with 120 mg/kg CY (BUCY-t) for 22 patients, and miscellaneous chemotherapy for two patients. The donors were HLA-identical or partially identical family members for 69 patients and unrelated donors for 42 patients. RESULTS: The 5-year disease-free survival was 8% for TBI, 19% for BUCY, and 30% for BUCY-t (P =.006). The 5-year cumulative incidence of relapse was 40% for secondary AML, 40% for RAEB-T, 26% for RAEB, and 0% for RA or RARS (P =.0009). The 5-year cumulative incidence of nonrelapse mortality after TBI was 58%; after BUCY, 52%; and after BUCY-t, 42% (P =.02). CONCLUSION: Patients at risk for treatment-related leukemia or myelodysplasia should be followed closely and be considered for stem-cell transplantation early in the course of myelodysplasia using conditioning regimens such as BUCY-t designed to reduce nonrelapse mortality.     

Role of cytokines in the treatment of acute leukemias: a review.

Myeloid growth factors, such as granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, have been used to decrease the duration of chemotherapy-induced neutropenia and thereby reduce the incidence and severity of infections in various regimens used to treat acute myeloid leukemia and acute lymphoblastic leukemia. These growth factors have also been used to recruit dormant myeloid leukemia cells into the S phase of cell cycle in order to increase their susceptibility to the antileukemic effects of agents such as cytarabine. Multiple prospective randomized trials have examined the benefit and safety of the addition of growth factors before, during, and after chemotherapy. A reduction in the duration of neutropenia has been the most consistent finding; this has not been associated with stimulation of leukemia cells, the main concern of using this strategy. Unfortunately, few studies have reported a benefit in prolonging the duration of disease-free survival or overall survival. Other cytokines, including interleukins and thrombopoietin, have also been evaluated for their theoretical ability to recruit immune mechanisms to eradicate residual leukemia burden after chemotherapy, and to stimulate platelet production. In this review, we summarize the clinical experience with these growth factors in treating acute leukemias.