硼替佐米和沙利度胺为主的化疗方案对伴有肾功能不全的多发性骨髓瘤患者的疗效比较

目的:观察以硼替佐米为主和沙利度胺为主的化疗方案治疗伴有肾功能不全的多发性骨髓瘤(MM)患者的疗效,探讨对伴有肾功能不全的MM治疗的最佳方案.方法:40例伴有肾功能不全的MM患者,其中初治20例,复发(难治)20例.选择20例使用以硼替佐米为主的化疗方案作为试验组,以同期20例接受沙利度胺为基础的联合化疗方案治疗的MM...     

硼替佐米联合地塞米松方案诱导后续不同方法巩固治疗多发性骨髓瘤长期疗效观察

目的比较以硼替佐米联合地塞米松(VD)方案诱导治疗达到完全缓解/接近完全缓解(CR/nCR)疗效的多发性骨髓瘤(MM)患者接受自体造血干细胞移植和VD方案作为不同巩固治疗的疗效和预后。方法回顾性分析2006年7月至2009年2月中山大学附属第一医院血液科23例经VD方案诱导达到CR/nCR疗效的MM患者的临床资料。16例(移植组)接受自体造血干细胞移植作为巩固,7例(非移植组)继续应用VD方案巩固2～4个疗程。两组患者巩固治疗后均接受50～200mg反应停维持治疗直至复发。结果移植组患者在巩固治疗后有7例患者(7/16,43.8%)疗效进一步增加,中位随访15个月时所有患者均存活,处于无疾病进展状态;非移植组在中位随访13个月时,2例患者疾病进展,再次诱导治疗无效死亡。VD方案不影响干细胞采集,所有患者的干细胞植入顺利,中位中性粒细胞恢复时间16d(10～30d),中位血小板恢复时间20d(9～100d)。VD方案的常见不良反应包括胃肠道(47.8%)、疲乏(26.1%)、血小板减少(26.1%)、周围神经炎(52.2%)和感染(26.1%),3～4级毒副反应发生率低。结论自体造血干细胞移植的地位仍不可替代,VD方案诱导化疗后以自体移植作为巩固,是治疗年轻MM患者的最佳选择。     

硼替佐米为主治疗多发性骨髓瘤的疗效与安全性临床观察

目的:研究以硼替佐米为主的联合化疗对多发性骨髓瘤(MM)的疗效及其不良反应。方法:回顾性分析52例MM患者,其中42例接受以硼替佐米为主的联合化疗方案:初发MM 31例,复发难治MM 11例;轻链型12例,非轻链型30例;肾功能正常27例,肾功能损害15例;另外10例接受传统型(含长春新碱+蒽环类+地塞米松)化疗方案。比较硼替佐米初治组与传统化疗组,硼替佐米治疗组中轻链型与非轻链型、肾功功能正常者与肾功能损害者的疗效。同时观察42例硼替佐米治疗患者的不良反应。结果:硼替佐米初治组总有效率(ORR)和完全缓解(CR)+非常好的部分缓解(VGPR)率分别为87.10%(27/31)和64.52%(20/31),分别优于传统化疗组的20.00%(2/10)和10.00%(1/10),2组比较均差异有统计学意义(均P0.05)。硼替佐米治疗组中非轻链型患者的ORR和CR+VGPR率分别为76.67%(23/30)和56.67%(17/30),分别高于轻链型患者的75.00%(9/12)和50.00%(6/12),但2组比较差异无统计学意义;肾功能正常患者的ORR和CR+VGPR率分别为77.78%(21/27)和59.26%(16/27),分别高于肾功能损害者的73.33(11/15)和46.67%(7/15),但2组比较差异亦无统计学意义。接受硼替佐米治疗的42例患者中,不良反应主要为乏力(28.57%、12/42)和周围神经炎(35.71%、15/42)。在给药途径方面,硼替佐米静脉给药组乏力和周围神经炎的发生率,均分别高于硼替佐米皮下注射组(42.86%∶14.28%,52.38%∶19.05%,均P0.05)。结论:以硼替佐米为主的方案治疗初发MM疗效优于传统化疗方案,肾功能不全患者可以安全使用。硼替佐米的主要不良反应为乏力和周围神经炎,不良反应可以耐受。硼替佐米皮下注射给药可以有效减少不良反应,安全性相对较高。     

VAD方案和VD方案治疗初诊多发性骨髓瘤的效果比较

目的比较VAD方案和VD方案治疗初诊多发性骨髓瘤的临床疗效及副作用。方法 70例MM患者依据治疗方案分为VAD组(59例)和VD组(11例)。VAD组接受长春新碱、阿霉素及地塞米松治疗;VD组接受硼替佐米联合地塞米松治疗。结果患者初次化疗前后血钙下降值、β2-微球蛋白下降值、Ig G和Ig A下降值在两组之间有统计学意义(P<0.05);血红蛋白增长值、白蛋白增长值、球蛋白下降值在两组间无统计学意义(P>0.05)。VAD组中相关症状改善占28.8%(17/59),VD组中占63.6%(7/11),两组相比有统计学意义(P<0.05)。VAD组主要不良反应为胃肠道反应、感染及末梢神经炎,有54.2%(32/59)的患者在初次化疗出现了相关不良反应,其中感染多在3度以上。VD组不良反应多为胃肠道反应、腹泻和末梢神经炎,有27.3%(3/11)出现症状,症状较轻,经停药和对症处理后症状消失或缓解。结论 VD方案对初诊MM患者的初次化疗中血钙、β2-微球蛋白、Ig G/Ig A恢复效果明显,症状改善率大于VAD组,同时其副作用较轻微,患者较易耐受,可在临床推广。     

071多发性骨髓瘤患者在化疗和异体干细胞移植后的长期随访

异体干细胞移植可能是治愈多发性骨髓瘤(MM)的一种有效方法。本文回顾性分析了MM患者异体干细胞移植后的临床疗效。方法　本研究包括 1 3例MM患者 ,中位年龄 41 (3 1～ 46)岁 ,1 0例接受异体骨髓移植(BMT) ,3例接受异体外周血干细胞移植 (PB SCT)。其中 1例在移植前已经获得完全缓解(CR) ,7例达到部分缓解 (PR) ,5例处于病情进展期。移植前 β2 微球蛋白 (β2 M)大于 2 5mg/L者 5例 ,Fish检测到 1 3q1 4缺失者 3例。骨髓抑制化疗方案包括环磷酰胺和全身放疗 ,其中 1 2例为 1 2Gy,1例为 1 3 2Gy。患者接受干细胞的平均数为 3 89…     

硼替佐米对多发性骨髓瘤骨病的作用及其机制探讨

目的观察硼替佐米联合地塞米松方案(BD方案)对多发性骨髓瘤(MM)骨痛的疗效并初步探讨其作用机制。方法观察2006年10月至2009年4月中山大学附属第一医院血液科收治的59例接受BD方案和33例接受VADM方案(长春新碱、阿霉素、地塞米松与马法兰联合)的MM患者骨痛缓解、活动能力改善及骨事件发生情况;用酶联免疫吸附试验(ELISA)检测其中25例患者治疗前后抗酒石酸酸性磷酸酶(TRACP-5b)、骨碱性磷酸酶(BALP)及Wnt信号通路抑制因子DKK1的浓度。结果BD组在骨痛缓解率、活动能力改善和骨相关事件发生率方面均优于VADM组[分别为75.7%对50.0%,64.9%对20.8%和13.8%对57.8%(P均<0.05)]。与化疗前相比,BD组患者化疗后BALP浓度升高[(15.90±11.88)U/L对(48.98±47.07)U/L],TRACP-5b水平下降[(4.04±1.92)U/L对(2.22±1.53)U/L],DKK1水平下降[(19.08±11.78)μg/L对(9.78±5.14)μg/L],差异有统计学意义(P均<0.05)。结论BD方案对MM患者骨病有显著疗效;可促进骨髓瘤患者...     

硼替佐米为主化疗方案治疗初治与复发难治多发性骨髓瘤近期疗效分析

目的:分析硼替佐米为主化疗方案治疗初治与复发难治多发性骨髓瘤(MM)患者的临床疗效和不良反应.方法:初治MM患者11例,复发、难治MM患者7例均采用VD方案化疗:硼替佐米1.0～1.3 mg/m2第1、4、8和11天快速静脉注射,地塞米松20 mg第1～4天(7例复发难治予地塞米松40 mg)静脉滴注,3周为1疗程,所...     

硼替佐米为主的联合方案治疗复发或难治性多发性骨髓瘤

目的 观察硼替佐米为主的联合方案治疗复发、难治性多发性骨髓瘤(MM)的疗效和不良反应,探讨应用硼替佐米治疗的最佳方案、剂量及疗程.方法 复发、难治性MM患者46例,均在3～4周的疗程内,给予硼替佐米1.3 mg/m2,1、4、8、11 d,同时联合地塞米松(D)、D+沙立度胺(T)、环磷酰胺(C)+D、米托蒽醌(M)+D、DC+鬼臼乙叉甙(E)+顺铂(P)和DT-P+阿霉素(A)+CE等化疗方案.采用国际骨髓瘤工作组(IMWG)标准判断疗效,并按美国国立癌症研究院不良事件通用命名标准(NCI CTCAE)(第3版)观察不良反应.以接受沙立度胺为基础的联合方案治疗的49例复发、难治MM作历史对照研究.结果 在可评估的43例患者,中位随访时间10个月,31例获得不同程度的缓解,总有效率为72.1%(对照组为51.0%,P＜0.05).其中完全缓解(CR)5例(11.6%),很好的部分缓解(VGPR)12例(27.9%),部分缓解(PR)14例(32.6%).接受1个疗程和2个疗程的总有效率分别为30.2%、58.1%(P＜0.05).常见的不良反应为血小板减少(62.8%)、乏力(55.8%)、恶心(51.2%)及周围神经病变(30.2%)等,但均能耐受.对照组的不良反应有便秘(69.4%)、乏力(59.2%)和头昏、头晕(46.9%)等.结论 硼替佐米为主的联合方案是一种对复发、难治性MM新的治疗选择,疗效优于沙立度胺为基础的联合方案,且两者毒性谱有所不同.     

不同化疗方案治疗多发性骨髓瘤的临床疗效观察

目的:观察并评价分别接受不同化疗方案[长春新碱+多柔比星+地塞米松(VAD)、马法兰+泼尼松+沙利度胺(MPT)和硼替佐米+地塞米松(VD)]对初治多发性骨髓瘤(MM)患者的疗效。方法:对确诊为MM的76例患者进行回顾性分析,其中28例采用VD方案,39例采用VAD方案,9例采用MPT方案,判定以上3种方案的疗效。结果:VD方案的疗效优于VAD和MPT方案(89.3%∶61.5%,P<0.05;89.3%∶33.3%,P<0.01),不良反应发生率低于VAD和MPT方案(35.7%∶66.7%,P<0.05;35.7%∶100%,P<0.01)。结论:VD方案治疗MM的疗效明显优于VAD和MPT方案,且不良反应较少,是一种值得推荐治疗MM的安全、可靠及有效的方法。     

PAD方案治疗初治多发性骨髓瘤的临床疗效

目的:评估PAD方案(硼替佐米+脂质体多柔比星+地塞米松)治疗初治多发性骨髓瘤(MM)的疗效和安全性。方法:初治MM 27例,均给予PAD方案为一线治疗:硼替佐米1.3mg/m2,静脉注射,第1、4、8、11天;脂质体多柔比星20mg,静脉滴注,第1、4、8天;地塞米松20~40mg/d,静脉滴注,第1、4、8、11天;每28d为1个周期。27例患者接受平均4(2~8)个疗程的治疗。观察其短期疗效和长期疗效,并判断其不良反应。结果:近期疗效观察:初始疗效的中位时间为2周,最佳疗效的中位时间为3个月。总反应率为89%,其中完全缓解14例(52%),非常好的部分缓解2例(7%),部分缓解8例(30%)。此外,疾病稳定3例(11%),疾病控制100%。长期疗效观察:中位随访49(7~96)个月,中位无进展生存时间24个月,中位生存时间50个月。患者3年、5年、7年的无疾病进展率分别为37.0%、17.3%和8.6%,3年、5年、7年的总生存率分别为51.9%、47.9%和47.9%。主要的不良反应为血液学毒性,中性粒细胞减少8例(30%),贫血5例(19%),血小板减少7例(26%)。非血液学毒性主要为胃肠道症状,便秘10例(37%),腹泻、恶心、黏膜炎分别为2例(7%);其次为周围神经病变,1/2级7例(26%),3级2例(7%)。4例(15%)出现手足综合征,4例(15%)出现乏力,2例(7%)肝功能异常,2例(7%)并发带状疱疹。结论:PAD方案对于初治MM总反应率高,起效快,不良反应较小,是一种安全、有效的治疗方法。其长期疗效显示,PAD方案能使MM获得最大程度的缓解,适当的维持治疗后近半数患者长期生存。     

A multi-centers clinical study of different treatment outcomes of 332 patients with multiple myeloma

OBJECTIVE: To describe the demographic and clinical characteristics of patients with the diagnosis of multiple myeloma (MM) and to analyse the outcome of different regimens for the treatment of MM. METHODS: The study reviewed 332 MM cases diagnosed within the period from January 1, 2002 to December 31, 2002. These patients were tracked via their records to a total period of three years. RESULTS: First-line treatment: Totally 332 patients were included, among them 325 (97.9%) patients received chemotherapy and 7 (2.1%) patients received stem cell transplantation (SCT); Second-line treatment: 197 patients were included, among them 190 (96.5%) patients received chemotherapy and 7 (3.6%) patients received SCT; Third-line treatment: 92 patients were included,among them 88 (95.7%) patients received chemotherapy and 4 (4.4%) patients received SCT. Major adverse effects were follows: severe infection 19.3%, severe anaemia 19.3%, phlebothrombosis 1.2% , thrombocytopenia 16.9%, fever associated with neutropenia 18.1%. CONCLUSIONS: Some curative effects can be achieved by using traditional treatment plans to treat patients suffering from MM, but new methods are expected to improve the prognosis.     

Intensification of the stem cell transplant induction regimen results in increased treatment-related mortality without improved outcome in multiple myeloma

Randomized trials conducted by the Intergroupe Fran?aise du Myelome (IFM) demonstrate that the use of high-dose chemotherapy (HDCT) and stem cell transplantation (SCT) improves event-free (EFS) and overall survival (OS) in younger patients with multiple myeloma (MM). Nevertheless, current HDCT regimens remain inadequate as all patients ultimately relapse following SCT. In an attempt to improve the OS of MM patients post-SCT we used an escalated HDCT regimen incorporating both intensified melphalan (160 mg/m2) and fractionated total body irradiation (12 Gy) to maximize the dose response of myeloma cells to these agents and included infusional etoposide 60 mg/kg in an attempt to eradicate clonal B cells potentially contributing to the myeloma clone. One hundred patients with MM received this intensified SCT regimen. The 100-day treatment-related mortality was 12% predominantly reflecting the development of interstitial pneumonitis (IP) in 28% of patients of whom 7/28 (25%) died. The predicted 5-year OS and EFS following the diagnosis of MM were 60% and 35%, respectively. The median OS from the time of transplant is 41 months and the median EFS is 28 months. More than two prior chemotherapy regimens, previous radiation therapy (RT) and the presence of an abnormal karyotype involving chromosomes 11 or 13 were significantly predictive of poor outcome. Interferon maintenance was not associated with improved outcome. Intensification of the HDCT regimen utilizing etoposide together with escalated melphalan and TBI increases morbidity and mortality without increasing OS beyond that reported with less toxic regimens.     

Long‐term outcome after allogeneic stem‐cell transplantation with reduced‐intensity conditioning in patients with multiple myeloma

This study examines the long‐term outcomes of a cohort of patients with myeloma who were treated with reduced‐intensity conditioning (RIC) regimens after a minimum follow‐up of 5 years at our centre. A total of 53 patients with multiple myeloma (MM) who received allogeneic hematopoietic stem‐cell transplantation (Allo‐SCT) between January 2000 and January 2007 were identified. The median follow‐up of living patients was 84 months (51–141). The median age of the MM patients was 50 (28–70) years. Fifty‐one patients (96%) received a transplant from a sibling donor. The median time between diagnosis and Allo‐SCT was 34 months (6–161), and the median time between auto‐SCT and Allo‐SCT was 10 months (1–89). Fifty‐one patients (96%) received at least one auto‐SCT; 24 patients (45%) received a tandem auto‐Allo‐SCT. At last follow‐up, 21 patients (40%) are alive > 5 years post RIC Allo‐SCT. At last follow‐up, 14 (26%) are in first complete remission (CR), and four patients (8%) in second CR after donor lymphocyte infusion or re‐induction with one of the new anti‐myeloma drugs (bortezomib or lenalidomide) after Allo‐SCT. Eight patients (38%) among these long survivors received one of these new drugs as induction or relapse treatment before Allo‐SCT. Disease status and occurrence of cGvHD were significantly associated with progression‐free survival (PFS); hazard ratio (HR) = 0.62 (0.30–1.29, P = 0.20). Acute GvHD was correlated with higher transplant‐related mortality; HR = 4.19 (1.05–16.77, P = 0.04). No variables were associated with overall survival (OS). In conclusion, we observe that long‐term disease control can be expected in a subset of MM patients undergoing RIC Allo‐SCT. After 10 years, the OS and PFS were 32% and 24%, respectively. The PFS curve after Allo‐SCT stabilizes in time with a plateau after 6 years post Allo‐SCT. Am. J. Hematol. 88:370–374, 2013. © 2013 Wiley Periodicals, Inc.     

Rituximab reduces relapse risk after allogeneic and autologous stem cell transplantation in patients with high-risk aggressive non-Hodgkin's lymphoma

High-dose chemotherapy and autologous stem cell transplantation (SCT) have limited success in patients with refractory aggressive lymphoma. Allogeneic SCT may offer some advantage in this setting by providing graft-versus-lymphoma effect, but the relapse risk remains substantial. In this study, we evaluated the safety and efficacy of rituximab administration after SCT in patients at high-risk for post-transplant relapse, in order to reduce relapse risk. Twenty-eight patients were included with the intent to treat them with rituximab after autologous (n = 16) or allogeneic (n = 12) SCT. Twenty-four were given rituximab starting a median of 47 d post SCT. Three died of SCT complications prior to therapy. Nine patients not achieving a complete remission (CR) post SCT converted to CR with rituximab and with the onset of graft-versus-host disease (GVHD) in three. With a median follow-up of 12 months (range, 3-33 months) the estimated 2-year overall survival and disease-free survival was 85 +/- 7% and 55 +/- 13% respectively. When only those patients who were actually treated are analysed, these rates were 95 +/- 7% and 64 +/- 13% respectively. The relapse risk was 35 +/- 14%. Seven patients had recurrent neutropenia episodes associated with severe hypogammaglobulinaemia, which were further prevented with intravenous immunoglobulin. None of the 10 allogeneic SCT recipients treated with rituximab had severe GVHD. Rituximab may be an effective adjuvant therapy after SCT to reduce the relapse rate and improve the outcome in high-risk aggressive lymphoma. Larger scale comparative trials are necessary to better define its role in SCT.     

SCT in patients with carbapenem resistant Klebsiella pneumoniae: a single center experience with oral gentamicin for the eradication of carrier state

Following an outbreak of carbapenem resistant Klebsiella pneumoniae (CRKP) bacteremia among inpatients in the Hemato-oncology and BMT unit, we studied the course of this infection in patients undergoing intensive chemotherapy and SCT. In addition, we conducted a pilot study aimed to eradicate CRKP colonization in the gastrointestinal tract, using oral gentamicin. Adult patients admitted to the BMT unit, identified as CRKP carriers on surveillance rectal cultures, were included in the study. Oral gentamicin at a dose of 80 mg q.i.d. was administered to all identified carriers until eradication. Among 15 colonized patients included in the study, the eradication rate achieved was 66% (10/15); discontinuation of persistent bacteremia occurred in 62.5% (5/8) and nosocomial spread of CRKP carrier state ceased. Administration of intensive chemotherapy and SCT is feasible, although associated with increased risk. Hematological patients in need of intensive chemotherapy/SCT should not be denied the required treatment on the basis of being CRKP carriers. Oral gentamicin treatment for eradication of CRKP from the gastrointestinal reservoir could serve as additional tool in the combat against the nosocomial spread and severe infections caused by this difficult-to-treat organism.     

Short and long-term outcome of treatment with high-dose melphalan and stem cell transplantation for multiple myeloma-associated AL amyloidosis

High-dose melphalan chemotherapy and autologous peripheral blood stem cell transplantation (HDM/SCT) has been shown to result in a durable hematologic response and prolonged overall survival in systemic amyloid light-chain (AL) amyloidosis as well as multiple myeloma. However, little is known about the myeloma associated with AL amyloidosis (MM/AL). In this retrospective study, we evaluated 87 patients with MM/AL from 1994 to 2007. Sixteen of these patients underwent HDM/SCT at Boston University Medical Center. Three patients (19%) died from treatment-related mortality. The overall median survival for all 87 patients was 22 months by Kaplan–Meier estimates. However, this was improved to 54.5 months for those who received HDM/SCT compared to 21 months for those who did not receive HDM/SCT. A hematologic complete response was achieved by 25% (4/16) of patients at 6 months after HDM/SCT. Hematologic relapses occurred in 60% of patients at a median of 1 year after HDM/SCT. In conclusion, HDM/SCT can prolong overall survival in patients with MM/AL who are eligible to receive it.     

Consolidative therapy with stem cell transplantation improves survival of patients with mantle cell lymphoma after any induction regimen

Intensive induction regimen followed by high-dose chemotherapy and autologous stem cell transplantation (auto-SCT) is frequently used to improve outcomes in patients with mantle-cell lymphoma. The comparative impact of conventional vs intensive induction regimen before transplantation is unknown. Forty-eight patients with mantle-cell lymphoma receiving SCT at our institution between January 2000 and December 2010 were included in this study. At the time of initial presentation, 43 (89.5%) had stage IV disease and 18 (37.5%) received more than one chemotherapy regimen before transplantation. Forty patients underwent auto-SCT and 7 had allogeneic SCT (allo-SCT); 1 patient had an allo-SCT for relapsed disease after auto-SCT. At the time of this analysis (median follow-up of 6 years from diagnosis and 4 years from transplantation), 40 patients (88%) were alive with a 5-year disease-free survival of 74.8%. Age, disease stage, number of regimens pre-SCT, pre-SCT disease status, and type of SCT had no impact on long-term outcomes. Importantly, there were no differences among the types of induction regimen on outcomes in this cohort receiving SCT. Based on our data, we believe that future studies should focus on strategies to prevent disease relapse rather than comparing induction regimens before stem cell transplantation.     

Invasive pulmonary aspergillosis in patients with hematologic malignancies: survival and prognostic factors

BACKGROUND AND OBJECTIVES: Despite improvements made in its early diagnosis and effective treatment, invasive pulmonary aspergillosis (IPA) remains a devastating opportunistic infection. In this retrospective study we have reviewed all consecutive cases of IPA diagnosed in adult patients with hematologic malignancies in our center from 1995 to 2000 to determine survival and prognostic factors. DESIGN AND METHODS: Forty-one patients were included in the study. Ante-mortem classification of cases of IPA were: 4 definite, 10 highly probable, 19 probable and 8 possible cases; all these last eight patients were later upgraded to definite IPA at post-mortem examination. Clinical charts were reviewed and factors possibly affecting the outcome of IPA were analyzed. RESULTS: All but two patients received chemotherapy and/or immunosuppresive therapy before the onset of IPA (conventional chemotherapy = 24, allogeneic stem cell transplantation [SCT] = 12, autologous SCT = 3). At IPA diagnosis 28 patients were neutropenic (< 0.5 x 10(9)/L) for a median of 25 days (range 7-135), and 10 allogeneic SCT patients were receiving corticosteroids for graft-versus-host-disease. All but two patients received antifungal treatment for IPA. The median delay from diagnosis to start of therapy was two days (range 0-20). The median follow-up after the first symptom or sign of IPA was 42 days with a maximum follow-up of 61 months. The actuarial 4-month infection-free survival was 40% (95% CI 25% to 55%). Thirty-three patients died during follow-up and IPA was implicated in the patients' death in 24 cases (75%). In multivariate analysis prolonged survival was associated with recovery of neutropenia during treatment (p = 0.001) and not having received an allogeneic SCT (p = 0.003). INTERPRETATION AND CONCLUSIONS: Despite prompt initiation of antifungal therapy, survival of patients with a hematologic malignancy and IPA is currently low. Perhaps the introduction of more sensitive diagnostic methods will allow the onset of intensive therapy prior to the appearance of more advanced clinical symptoms and/or radiological signs, and the time will come to test whether earlier and more intensive therapy will improve survival.     

The natural history and treatment outcome of blast phase BCR-ABL- myeloproliferative neoplasms

We analyzed the outcomes of 74 patients diagnosed with BCR-ABL(-) myeloproliferative neoplasms in blast phase receiving induction chemotherapy (55%), low-intensity therapy (16%), stem cell transplantation (SCT; 3%), or supportive care (26%). Median survival from the date of blastic transformation was 5 months. Patients receiving supportive therapy had a median survival of 6 weeks. Complete remission with or without blood recovery was achieved in 46% of patients receiving induction chemotherapy, but remissions were not durable with a median progression-free survival of only 5 months. Eight patients received SCT either as first therapy or after responding to antileukemia therapy. These patients had a markedly superior survival, with 73% alive at a median follow-up of 31 months. JAK2V617F kinetics were assessed in 16 patients: 0 of 4 negative patients became positive at transformation, and among 12 positive patients, 1 had an increase in JAK2V617F% at transformation, 7 had a substantial decrease, and 4 had stable levels. Myeloproliferative neoplasm blast phase is associated with a dismal prognosis. Responses to chemotherapy can be achieved but are not durable. Long-term survivors had all received SCT either as first therapy or in first remission.     

Results of autologous stem cell transplant in multiple myeloma patients with renal failure

Data are presented on 81 multiple myeloma (MM) patients with renal failure (creatinine > 176.8 micromol/l) at the time of autologous stem cell transplantation (auto-SCT), including 38 patients on dialysis. The median age was 53 years (range: 29-69) and 26% had received more than 12 months of prior chemotherapy. CD34+ cells were mobilized with granulocyte colony-stimulating factor (G-CSF) alone (n = 51) or chemotherapy plus G-CSF (n = 27), yielding medians of 10 and 16 x 106 CD34+ cells/kg respectively (P = 0.003). Sixty patients (27 on dialysis) received melphalan 200 mg/m2 (MEL-200). Because of excessive toxicity, the subsequent 21 patients (11 on dialysis) received MEL 140 mg/m2 (MEL-140). Thirty-one patients (38%) completed tandem auto-SCT, including 11 on dialysis. Treatment-related mortality (TRM) was 6% and 13% after the first and second auto-SCT. Median times to absolute neutrophil count (ANC) > 0.5 x 109/l and to platelets > 50 x 109/l were 11 and 41 d respectively. Non-haematological toxicities included mucositis, pneumonitis, dysrhythmias and encephalopathy. At a median follow up of 31 months, 30 patients have died. Complete remission (CR) was achieved in 21 patients (26%) after first SCT and 31 patients (38%) after tandem SCT. Two patients discontinued dialysis after SCT. Median durations of complete remission (CR) and overall survival (OS) have not been reached; probabilities of event-free survival (EFS) and OS at 3 years were 48% and 55% respectively. Dialysis dependence and MEL dose did not affect EFS or OS. Sensitive disease prior to SCT, normal albumin level and younger age were independent prognostic factors for better OS. In conclusion, renal failure had no impact on the quality of stem cell collections and did not affect engraftment. MEL-140 had an acceptable toxicity and appeared equally effective as MEL-200. In the setting of renal failure, the role of auto-SCT early in the disease course and benefits of tandem SCT require further evaluation.