自体及非清髓异基因造血干细胞移植治疗多发性骨髓瘤一例

异基因造血干细胞移植是目前可以治愈多发性骨髓瘤(MM)的方法之一。为了降低治疗相关死亡率，减少复发，我们对1例多发性骨髓瘤患者进行了2次移植。第1次为自体外周血造血干细胞移植，第2次为非清髓性异基因外周血造血干细胞移植。现报告如下。     

自体外周血干细胞移植治疗多发性骨髓瘤下肢缺血性坏死一例

患者男,59岁,患多发性骨髓瘤（multiple myeloma,MM） 8年,1999年4月实施外周血干细胞移植治疗。2003年3月实施半身交替照射（double hemi-body irradiation,DHBI）治疗。6个月前患者左下肢逐渐变黑色,踝关节处见破溃并少量渗出,行走受限并疼痛,诊断为下肢缺血性坏死。2005年5月5日入我院,行自体外周血干细胞移植治疗。     

自体外周血干细胞移植治疗早期成人股骨头坏死

目的 探讨应用髓芯减压+人工可诱导骨基质+自体外周血干细胞移植治疗股骨头缺血性坏死的疗效.方法 2006年1月至2008年7月对12例(16髋)早期股骨头坏死患者髋关节采用髓芯减压+人工可诱导骨基质+自体外周血干细胞移植治疗,其中男9例,女3例;年龄32～55岁,平均39.2岁;股骨头坏死按Ficat分期:Ⅰ期5髋,Ⅱ期8髋,Ⅲ期3髋.术前均有髋关节疼痛、跛行、活动受限等症状.结果 所有患者术后获12～16个月(平均14.3个月)随访,疼痛均消失,行走正常,髋关节活动范围正常或接近正常.术后患者满意度:优4髋,良10髋,可1髋,差1髋,优良率为87.5%.本组患者术后1年疼痛评分、Harris评分、髋关节前屈、外旋、内旋与术前比较差异均有统计学意义(P＜0.05).结论 髋关节髓芯减压+人工可诱导骨基质+自体外周血干细胞移植治疗早期股骨头坏死损伤小、操作简单、短期疗效满意.     

外周血干细胞移植治疗慢性下肢动脉缺血性疾病

目的 观察自体外周血干细胞移植治疗慢性下肢缺血性疾病的疗效.方法 应用自体外周血干细胞移植治疗46例慢性下肢缺血性疾病的患者.结果 42例小腿疼痛缓解,小腿冷、凉感觉消失;35例足部疼痛改善;29例足部冷、凉感消失;4例术后4周因为小腿中段以下出现坏死导致截肢.42例保肢病例,干细胞移植术后3个月,间歇性跛行距离由(87.45±41.22)m增加到(348.52±147.24)m,下肢皮温由(28.52±0.51)℃增加到(33.56±0.62)℃,踝肱指数(ABI)由(0.48±0.06)增加到(0.75±0.07),移植前后3项指标的差异均具有统计学意义(P＜0.05),移植后优于移植前.术后6个月和12个月下肢动脉影像学检查显示,37例均有不同程度的新生侧支血管形成.结论 自体外周血干细胞移植治疗下肢缺血性疾病是一种有效的方法,尤其对远端动脉流出道差的患者是一种较好的治疗手段.     

自体外周血造血干细胞移植治疗系统性红斑狼疮的临床观察

目的观察自体外周血造血干细胞移植治疗系统性红斑狼疮（SLE）的临床疗效。方法5例对其他治疗效果反应较差的复发SLE患者接受自体外周血造血干细胞移植术，造血干细胞动员方案采用环磷酰胺＋粒细胞集落刺激因子，应用CS-3000 Plus血细胞分离机采集外周血干细胞，预处理方案采用环磷酰胺＋抗胸腺球蛋白抗体方案，常规措施预防移植相关并发症。移植后3个月，复查各项免疫指标，评估疗效。结果5例患者造血干细胞动员均获成功，造血重建顺利回输后外周血中性粒细胞计数≥0．5×10^9／L的天数为8。16d；白细胞总数恢复正常的天数为10-20d：血小板计数〉20×10^9／L的天数为12～20d。无一例出现严重的移植后并发症。临床症状明显改善或消失。3个月后复查各项指标均较移植前有明显改善。结论自体外周血造血干细胞移植治疗SLE的临床疗效好，不良反应少，是治疗难治性SLE的一种较好的方法。     

髓芯减压＋自体外周血干细胞移植治疗早期股骨头缺血性坏死

目的探讨应用髓芯减压＋自体外周血干细胞移植治疗股骨头缺血性坏死（ANFH）的疗效。方法对61例Ⅰ、Ⅱ期的ANFH患者采用髋关节髓芯减压入路＋自体外周血干细胞移植方法治疗。结果所有患者随访6～32个月,疼痛均消失,行走正常,髋关节活动范围正常或接近正常,CT或MRI片示股骨头轮廓清晰,囊性变消失,骨密度均匀,关节间隙正常。结论髋关节髓芯减压＋自体外周血干细胞移植手术治疗早期ANFH具有损伤小、简便、准确、有效的优点。     

自体外周血干细胞移植治疗患者下肢动脉缺血性疾病的随访研究

目的对16例自体外周血干细胞（PBSC）移植治疗下肢动脉缺血性溃疡的患者进行长期的随访。方法自2004年3月至2007年2月，我科利用自体外周血干细胞技术治疗了16例患有严重下肢动脉缺血性溃疡的患者，对患者进行长期的包括肢体疼痛、活动情况、下肢动脉磁共振血管成像（MRA）等随访检查。使用G—CSF5-6天动员患者骨髓干细胞进入周围循环，第六天使用细胞分离器采集周围血干细胞，然后肌注到患肢缺血的肌肉内。结果移植后经过10～45个月的追踪随访，15例患者静息痛缓解，11例溃疡愈合，4例失访，间歇性跛行时间及距离延长。结论通过对白体外周血干细胞移植治疗患者下肢动脉缺血性溃疡的随访显示，应用自体外周血干细胞移植技术治疗下肢动脉缺血性疾病是可行且有效的，是治疗肢体缺血性疾病的一种新手段，值得进一步研究和探讨。     

异基因外周血造血干细胞移植治疗多发性骨髓瘤二例

多发性骨髓瘤(MM)为浆细胞恶性克隆增生性疾病,传统化疗和自体造血干细胞移植虽可使疾病得到暂时缓解,但最终不免复发和进展,患者的中位存活时间仅3～4年。异基因造血干细胞移植是目前惟一可治愈该病的方法,我院采用外周血造血干细胞移植治疗多发性骨髓瘤2例,报告如下。     

自体外周血干细胞移植治疗下肢动脉缺血性疾病的临床应用

目的探讨自体外周血干细胞移植技术治疗下肢动脉缺血性疾病的可行性及存在的问题。方法自2004年3月至2007年2月期间，我院采用自体外周血干细胞技术治疗16例患有严重下肢动脉缺血性疾病的患者，通过采用重组粒细胞集落刺激因子动员骨髓干细胞增殖并释放入血，在动员的第5～6d，通过CS-3000 PLUS血细胞分离机进行外周血干细胞采集，并将采集到的浓缩干细胞液做缺血肢体肌肉注射。结果经治疗后3～24个月的追踪随访，息肢静息痛缓解，溃疡愈合，间歇性跛行时间及距离延长。结论应用自体外周血干细胞移植技术治疗下肢动脉缺血性疾病是可行且有效的，是治疗缺血性疾病的一种新手段，但该治疗方法处在临床治疗的初级阶段，尚需进一步研究和探讨。     

进展型多发性硬化患者输注自体外周造血干细胞的护理

对14例进展型多发性硬化患者行输注自体外周造血干细胞治疗.结果14例患者无1例移植相关死亡,移植后神经损害得到改善.提出输注前做好心理护理,配合采集造血干细胞,观察预处理化疗药物毒副反应;输注中注意滴速;输注后积极预防感染与出血是其配合重点.     

The first 2 years of clinical experience with peripheral blood stem cell transplantation for various hematological malignancies: results from a single Baskent University Center

Autologous stem cell transplantation is the current standard approach for patients with multiple myeloma and relapsed or refractory lymphoma. Nonmyeloablative allogeneic stem cell transplantation has been applied worldwide. We analyzed the results of transplantation activity from 2004 to 2006. Seven evaluable patients younger than 65 years old with stage II/III multiple myeloma were treated with high-dose melphalan therapy (140 mg/m(2)) plus autologous peripheral blood stem cell transplantation. Complete responses or tumor reductions of more than 75% were obtained in all patients. At a median follow-up of 10 months, all patients remained disease-free. Four patients with acute myeloblastic leukemia underwent nonmyeloablative allogeneic peripheral stem cell transplantation. Their median age was 30 years. One patient was refractory and the others were in hematological remission. The patients received fludarabine-based preparative regimens. All patients received fully matched blood from a related donor 2 days after chemotherapy in conjunction with graft-versus-host disease prophylaxis. One refractory patient with >90% engraftment had late autologous reconstitution at 3 months with evidence of relapse. All other patients in remission remained with >90% donor cell engraftment. These patients are disease-free at 13, 10, and 2 months. Toxicity was minimal. These results showed promise due to the minimal toxicity observed with the conditioning regimens which indicated the feasibility of these procedures.     

Cardiac surgery in a patient with multiple myeloma combined with renal amyloidosis

We present a case of a 62-year-old woman who underwent mitral valve and aortic valve replacement owing to infective endocarditis. Previously, the patient had been diagnosed with renal amyloidosis and multiple myeloma. She underwent chemotherapy and autologous peripheral blood stem cell transplantation and has achieved nearly complete remission. The patient’s postoperative course was almost uneventful, and she was discharged on the 22nd postoperative day. This is the first case report about cardiac surgery for the patient with multiple myeloma combined with renal amyloidosis.     

Resolution of mesangial light chain deposits 3 years after high-dose melphalan with autologous peripheral blood stem cell transplantation

A 52-year-old woman was admitted to our hospital for treatment of nephrotic syndrome. Funduscopic findings showed fundal hemorrhage and soft exudates, and serologic analysis showed a monoclonal serum component that was identified as Bence Jones protein-k type. A bone marrow biopsy showed diffuse proliferation of atypical plasma cells, while a renal biopsy showed diffuse and nodular mesangial proliferation. Immunohistochemical staining confirmed the presence of k chains along the glomerular basement membrane and in mesangial areas. The patient was diagnosed as multiple myeloma (Bence Jones k type) with light chain deposition disease (LCDD). After high-dose melphalan and autologous peripheral blood stem cell transplantation (PBSCT), the multiple myeloma and nephrotic syndrome were in complete remission; her renal function was improved, but a renal biopsy performed 6 months after PBSCT showed the persistence of diffuse and nodular lesions. By contrast, a renal biopsy performed 3 years later showed complete resolution of the diffuse and nodular mesangial proliferation.     

Metachronous development of nonamyloidogenic [lambda] light chain deposition disease and IgG heavy chain amyloidosis in the same patient

We report a highly unusual case of monoclonal immunoglobulin deposition disease-associated nephrotic syndrome in which a patient developed both lambda light chain deposition disease and 6 years afterward IgG-heavy chain amyloidosis. The patient initially underwent autologous peripheral blood stem cell transplantation as treatment of the underlying plasma cell dyscrasia causing the light chain deposition disease-related nephrotic syndrome. After 6 years of clinical remission, recurrence of the nephrotic syndrome led to a renal biopsy demonstrating IgG-heavy chain amyloidosis. Interestingly, much of the characteristic nodular glomerular sclerosis seen in light chain deposition disease regressed between the time of the first biopsy and the second. Given the length of time between the development of the two diseases and the apparent success of stem cell transplantation in treating the first, we think that the patient produced two distinctly different abnormal plasma cell clones. To our knowledge, this is the first report of two different monoclonal immunoglobulin deposition diseases occurring in the same patient.     

Triple transplantation of autologous peripheral blood stem cells each time following conditioning with 100 mg/m2 of melphalan for multiple myeloma patients in poor performance status

Approximately one third of multiple myeloma patients (below 60 years) are diagnosed either in advanced disease or with significant comorbidities. Many other patients referred to transplant centers have already been heavily pretreated with multiple courses of various conventional chemotherapies. These patients are frequently in bad or even grave clinical condition; they are unlikely to survive standard high-dose melphalan (200 mg/m(3)) chemotherapy and autologous hematopoietic stem cell transplantation. Palumbo et al reported a protocol for elderly patients that utilized reduced conditioning (melphalan 100 mg/m(2) three times at 2-month intervals, each time supported by autologous hematopoietic rescue). We have used this protocol as a start to develop a method to induce a remission in the aforementioned subgroup of myeloma patients. Patients with stage III disease and WHO performance status 2 or higher are treated with one or two cycles of cyclophosphamide (2 to 4 g/m(2)) and undergo peripheral blood stem cells collection. Subsequently, they are treated with three to four doses of melphalan (100 mg/m(2)) at 8- to 12-weeks intervals each time supported by infusion of peripheral blood stem cells. To date 13 patients have been entered into the protocol. With one exception of transiently stable disease, the remaining patients obtained at least partial remission and three, complete remission. The compliance was good and better with each subsequent course. For half of the patients the problem was a short duration of response. This method when developed may offer a new treatment alternative for a subgroup of high-risk multiple myeloma patients.     

Successful treatment of nephrotic syndrome due to systemic AL amyloidosis after autologous stem cell transplantation: renal response is an important therapeutic end point

Primary systemic (AL) amyloidosis involves vital organs from the early phase of illness, resulting in poor prognosis. Today, high-dose melphalan followed by autologous peripheral blood stem cell transplantation is an effective treatment for systemic AL amyloidosis. We report a patient with nephrotic syndrome due to systemic AL amyloidosis, who was successfully treated with autologous peripheral blood stem cell transplantation. At follow-up 36 months from ASCT, the patient showed a significant improvement in the signs of peripheral neuropathy and reduction in proteinuria without further organ involvement. Due to poor prognosis with conventional therapy, autologous stem cell transplantation should be considered for treatment in patients with systemic AL amyloidosis, and favorable outcome is ensured with achievement of renal response after ASCT.     

Successful Treatment of Renal Failure Caused by Multiple Myeloma With HLA-Identical Living Kidney and Bone Marrow Transplantation: A Case Report

Here we have described a successful HLA-identical living allogeneic kidney transplantation after bone marrow transplantation in a patient with end-stag liver disease caused by multiple myeloma (MM). Our case is unique, because this combined transplantation is rarely possible and because of our unique immunosuppressive and management strategies. A 45-year-old man with ESRD MM and κ light-chain nephropathy was diagnosed. Cytostatic treatment resulted in partial remission, so autologous peripheral stem cell transplantation (SCT) was performed leading to a complete remission; however the patient remained anuric. The patient's HLA-identical brother offered to be a donor of peripheral stem cells for collection and cryopreservation. Kidney transplantation was performed with a combination of tacrolimus sirolimuns, and methylprednisolone. With a well-functioning kidney graft, allogeneic SCT was performed in the incipient relapse phase of MM, after total body irradiation. Severe oropharyngeal infections, diarrhea, sepsis, and renal failure. Fearing acute renal rejection, we administered steroid bolus. He experienced therapy with gradual restoration of kidney function. Then, steroid-responsive acute graft-versus-host disease (grade II, predominantly bowel) was diagnosed on the background of diarrhea, which returned once. Later he experienced a left subclavian vein thrombosis at the site of a central venous catheter and sepsis. Having recovered from these events, the patient enjoys good health, with stable kidney function and normal protein excretion. After the steroid was stopped, a bone marrow biopsy revealed full-donor type normocellular hemopoiesis. Because of the chimerism, we gradually discontinued the immunosuppression including, sirolimus and finally tacrolimus, since with minimal trough levels there were no complications. Bone marrow biopsy showed a complete remission. In MM with ESRD HLA-identical combined kidney and bone marrow transplantation from a living donor may offer not only complete remission and good renal function, but also good health without immunosuppression.     

Cure of malignant lymphoma in dogs with peripheral blood stem cell transplantation

Twelve dogs with spontaneous malignant lymphoma in chemotherapy-induced remission were treated with total-body irradiation (TBI) and transplantation of autologous peripheral blood mononuclear cells collected following chemotherapy-induced expansion of the stem cell pool. Four animals (33%) died of transplant-related complications, five (41%) relapsed, and three (25%) are long-term disease-free survivors. Recovery to 1000 white cells/mm3 occurred by day 16 and dogs no longer required platelet transfusions by day 37. With the exception of delayed platelet recovery these results are virtually identical to those previously reported using autologous bone marrow transplantation for canine lymphoma. This study therefore suggests that autologous peripheral blood mononuclear cells collected following chemotherapy-induced expansion of the stem cell pool may offer a realistic alternative to autologous marrow transplantation in patients with malignant lymphoma for whom autologous marrow is not available.     

Multicentric Castleman disease with secondary AA renal amyloidosis, nephrotic syndrome and chronic renal failure, remission after high-dose melphalan and autologous stem cell transplantation

Multicentric Castleman disease is a systemic lymphoproliferative disease with incomplete understood etiology. The various renal complications of this disease may include minimal change disease, mesangial proliferative glomerulonephritis, membranous glomerulonephritis and nephrotic syndrome, caused by secondary amyloidosis. In several reported cases of localized Castleman disease associated with renal amyloidosis and nephrotic syndrome, resection of organs involved by lymphoid proliferation resulted in complete remission. However, therapy of multicentric Castleman disease with renal amyloidosis is not well-established. We treated a case of a 39-year-old woman with multicentric Castleman disease complicated by nephrotic syndrome caused by secondary AA amyloidosis. The patient underwent autologous peripheral blood stem cell transplantation (auto-PBSCT), achieving complete remission. Autologous stem cell transplantation may be an attractive choice in therapy for refractory multicentric Castleman disease.     

Cerebellar aspergillosis: case report and literature review

OBJECTIVE AND IMPORTANCE: An unusual, but not unique, case of cerebellar aspergillosis associated with autologous peripheral blood stem cell transplantation for breast cancer is presented. CLINICAL PRESENTATION: A 45-year-old woman with breast cancer underwent chemotherapy and radiotherapy as well as autologous peripheral blood stem cell transplantation. She developed a cerebellar aspergillosis abscess that was treated successfully with two surgical resections. INTERVENTION: After removal of pus and the abscess wall, the patient received local application of amphotericin B (AmB). She received AmB 1 mg/kg/d for 3 months and itraconazole 100 mg/kg/d for 1 year. After 3 months of AmB treatment, magnetic resonance imaging revealed that disease had not recurred. CONCLUSION: In cases of central nervous system aspergillosis, to increase the therapeutic efficiency, AmB can also be applied to the abscess cavity. Computed tomographic and contrast-enhanced magnetic resonance imaging scans play an important role in establishing early diagnosis in high-risk, immunocompromised patients.