Therapeutic plasma exchange in patients with grade 2-3 hematopoietic stem cell transplantation-associated thrombotic thrombocytopenic purpura: a ten-year experience

In the present retrospective study we report our 10-year experience with therapeutic plasma exchange (TPE) in 18 patients with grade 2-3 hematopoietic stem cell transplantation (HSCT)-associated thrombotic thrombocytopenic purpura (TTP). During TPE a mean total quantity of 26.5 +/- 15.1 L of plasma was exchanged. Five patients (27.7%) had a complete response eight patients (44.4%) had a partial response while five patients (27.7%) died during TPE treatment. Among the survivors, relapse of TTP occured in three patients (23%) and although these patients were treated again with TPE, all died. First-year survival rate was 41.2%. Our results indicate that TPE may be effective in the treatment of some patients with grade 2-3 HSCT-associated TTP.     

Fatal thrombotic thrombocytopenic purpura as a rare complication following allogeneic stem cell transplantation

 Thrombotic thrombocytopenic purpura (TTP) is a rare disease which, together with hemolytic uremic syndrome, is subsumed under thrombotic microangiopathy. After stem cell transplantation (SCT), this syndrome represents a possibly fatal complication with a higher incidence in allogeneic SCT than in autologous SCT. Although plasmapheresis offers an encouraging treatment modality in classic TTP, this seems less effective in bone marrow transplant-associated microangiopathy. This is probably due to a different etiology. We present a case of transplant-associated TTP with a fatal outcome despite multiple courses of plasmapheresis. Received: 11 November 1999 / Accepted: 23 February 2000     

A case of thrombotic thrombocytopenic purpura in an adult treated with vincristine

 The case of a woman with thrombotic thrombocytopenic purpura refractory to prolonged treatment with plasma exchange and steroid treatment is described. The addition of vincristine yielded a complete response, which has been maintained for 9 months up to the time of this report. Received: May 29, 1998 / Accepted: September 11, 1998     

Successful treatment of thrombotic thrombocytopenic purpura with repeated plasma exchange in a patient with microscopic polyangitis

Thrombotic thrombocytopenic purpura (TTP) is in rare cases associated with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, and often has a fatal outcome. We report the case of a 77-year-old woman with microscopic polyangitis (MPA) presenting with TTP. Rapidly progressive renal dysfunction and paralysis and sensory disturbance of the left lower limb were noted. Serum creatinine was 3.95 mg/dl, and the titer of myeloperoxidase-ANCA was 238 EU. She was diagnosed with MPA, and high-dose methylprednisolone was initiated, followed by 60 mg/day of prednisolone. Hemolytic anemia with red blood cell fragmentation, purpura, and thrombocytopenia developed during the course of active MPA. The activity of disintegrin and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) was moderately decreased (27%). She was diagnosed with TTP, and plasma infusion was initiated, followed by plasma exchange (PE) with 40 units of fresh frozen plasma. Thrombocytopenia continued for more than a month (5–10 × 10⁴/μl). PE was repeatedly performed two or three times a week during the first 8 weeks from the beginning of PE in addition to prednisolone. Her clinical and laboratory findings gradually improved, and ADAMTS13 activity increased to 68%. The findings in this case suggested that ANCA-associated vasculitis may be involved in the development and the pathogenesis of TTP, and that repeated PE may need to be performed in addition to immunosuppressive therapy.     

Successful treatment of thrombotic thrombocytopenic purpura with repeated plasma exchange in a patient with microscopic polyangitis

Abstract

Thrombotic thrombocytopenic purpura (TTP) is in rare cases associated with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, and often has a fatal outcome. We report the case of a 77-year-old woman with microscopic polyangitis (MPA) presenting with TTP. Rapidly progressive renal dysfunction and paralysis and sensory disturbance of the left lower limb were noted. Serum creatinine was 3.95 mg/dl, and the titer of myeloperoxidase-ANCA was 238 EU. She was diagnosed with MPA, and high-dose methylprednisolone was initiated, followed by 60 mg/day of prednisolone. Hemolytic anemia with red blood cell fragmentation, purpura, and thrombocytopenia developed during the course of active MPA. The activity of disintegrin and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) was moderately decreased (27%). She was diagnosed with TTP, and plasma infusion was initiated, followed by plasma exchange (PE) with 40 units of fresh frozen plasma. Thrombocytopenia continued for more than a month (5–10 × 10⁴/μl). PE was repeatedly performed two or three times a week during the first 8 weeks from the beginning of PE in addition to prednisolone. Her clinical and laboratory findings gradually improved, and ADAMTS13 activity increased to 68%. The findings in this case suggested that ANCA-associated vasculitis may be involved in the development and the pathogenesis of TTP, and that repeated PE may need to be performed in addition to immunosuppressive therapy.     

A case report of total abdominal hysterectomy resulting in acute thrombotic thrombocytopenic purpura with pancreatitis and hepatitis: complete resolution with plasma exchange therapy

Acute thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder that has previously been described associated with various types of surgery. An association between total abdominal hysterectomy (TAH) and TTP has never been reported. Thrombotic thrombocytopenic purpura is classically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, azotemia and neurological manifestations. Atypical manifestations of TTP include hepatitis, pancreatitis, acute respiratory distress syndrome, non-occlusive mesenteric ischemia and peripheral digital ischemia. This case report describes the occurrence of acute TTP following TAH and bilateral salpingo-oopherectomy, which manifested with typical and atypical features (i.e. hepatitis, pancreatitis). Plasma exchange therapy resulted in the complete resolution of the process.     

Citrate anticoagulation during plasma exchange in a patient with thrombotic thrombocytopenic purpura: short heparin-free hemodialysis helps to attenuate citrate load

The treatment of thrombotic thrombocytopenic purpura requires plasma exchange using fresh frozen plasma as a replacement solution once or even twice daily. If citrate anticoagulation is needed, the citrate load (both from fresh frozen plasma and citrate as an anticoagulant) can be significant, causing metabolic complications. The aim of our report is to present our experience with citrate anticoagulation in a patient with thrombotic thrombocytopenic purpura treated with daily membrane plasma exchange. Twenty-six plasma exchange procedures were performed during 20 days of treatment in a 46-year-old female. The blood flow was 98 +/- 8 mL/min; 4% trisodium citrate was infused into the arterial line (134 +/- 11 mL/h) and 1 M CaCl2 into the venous line (11.4 +/- 1.8 mL/h). Fresh frozen plasma (first 7 procedures) or cryo-poor plasma (19 procedures) were used as a replacement solution, 3176 +/- 536 mL per procedure. A total of 88,930 mL of plasma was exchanged. No serious side-effects occurred. iCa before plasma exchange was significantly higher than afterwards (1.23 +/- 0.12 vs. 1.12 +/- 0.12, P = 0.0047). Significant alkalosis occurred after three plasma exchanges (pH 7.64, bicarbonate 36.2 mmol/L), and was corrected by 3-h heparin-free hemodialysis with dialysate as follows: K 4.0 mmol/L, calcium 1.5 mmol/L, and bicarbonate set to 24 mmol/L. After dialysis, pH was 7.45 and bicarbonate 29.4 mmol/L. Another (2-h) heparin-free hemodialysis procedure was repeated after six plasma exchanges. Citrate anticoagulation can be safely performed in patients treated with plasma exchange once or twice daily. Periodically performed short heparin-free hemodialysis can correct metabolic alkalosis and attenuate the citrate load.     

A case report of transfusion-related acute lung injury during plasma exchange therapy for thrombotic thrombocytopenia purpura

Transfusion-related acute lung injury (TRALI) is a transfusion reaction that is often under recognized and underreported. Implications for diagnosis not only influence treatment considerations but also extend to donor selection, donor deferral and ultimately the safety of the final blood product. We report a case of a previously well 19-year-old female who presented a one week history of flu-like symptoms and mucosal bleeding. Laboratory results confirmed the diagnosis of thrombotic thrombocytopaenia purpura (TTP) and she was commenced on plasma exchange. During her second day of plasma exchange, she developed dyspnoea and rigors. Examination and investigation findings were consistent with a clinical diagnosis of TRALI. Granulocytes immunofluorescent test (GIFT - flow cytometry) was performed and cross reactivity was demonstrated between the patient's granulocytes and plasma from one of the nine donor fresh frozen plasma (FFP) packs. She made a full recovery. TRALIa accounts for 7% of all adverse events reported in the Serious Hazards of Transfusion (SHOT) database and has a mortality rate between 5-25%. Apheresis patients are a particularly vulnerable group of patients where clinical recognition and rapid laboratory confirmation of TRALI is imperative to minimize the risk of further patient exposure to donor granulocyte or human leukocyte antigen (HLA) antibodies. The provision of plasma from male donors may additionally reduce exposure. On a wider scale, rapid donor identification and deferral maintains the safety of the national blood supply.     

Successful treatment with allogeneic peripheral blood stem cell transplantation and granulocyte transfusion for severe aplastic anemia with sinusitis

A 43-year-old woman with severe aplastic anemia (SAA) received anti-thymocyte globulin and cyclosporin A (CyA) and achieved hematological remission. Although she had maintained hematological remission, the disease relapsed 10 months after arbitrary discontinuance of maintenance therapy with CyA. Resumption of CyA therapy was not effective, and her condition became complicated with progressive sinusitis with bone destruction, which was refractory to antibiotics, antifungal agents, granulocyte colony-stimulating factor, and surgical drainage. Because of the necessity for early neutrophil recovery (to resolve the infection), we proceeded with a combination therapy using allogeneic peripheral blood stem cell transplantation (PBSCT) promptly followed by granulocyte transfusion (GTX) from the same human leukocyte antigen-identical donor rather than carrying out a second immunosuppressive therapy. The patient showed temporal resolution of infection on the second day after a single GTX. Although the patient had pneumonia on day 11, it was resolved promptly after engraftment on day 16. This report suggests the clinical utility of a salvage therapy with allogeneic PBSCT followed by GTX in a particular case of recurrent SAA with refractory infections.     

Invasive fungal infections after allogeneic peripheral blood stem cell transplantation: incidence and risk factors in 395 patients

We have analysed the incidence and risk factors for the occurrence of invasive fungal infections (IFI) among 395 recipients of an allogeneic peripheral blood stem cell transplantation (PBSCT) from a human leucocyte antigen (HLA)-identical sibling. IFI (n = 50) occurred in 46 patients, giving an overall probability of 14%. There were 12 cases of invasive candidiasis (3%), with only one death. Non-Candida IFI occurred in 37 patients (12% probability), mostly invasive aspergillosis (n = 32). In multivariate analysis the only two significant variables associated with a higher risk of developing a non-Candida IFI were the development of moderate-to-severe graft-versus-host disease (GvHD, P < 0.0001; OR 4.6) and having received steroid prophylaxis for GvHD (P = 0.04; OR 2.1). In multivariate analysis the variables associated with a lower overall survival after PBSCT were development of a non-Candida IFI (P < 0.0001; OR 5.6), non-early disease phase (P = 0.0001; OR 1.9), steroid prophylaxis (P = 0.02; OR 1.4), moderate-to-severe GvHD (P = 0.01; OR 1.6) and cytomegalovirus infection post transplant (P = 0.001; OR 1.8). Our results show that non-Candida IFI (in particular aspergillosis) was an important cause of infectious morbidity and mortality after an HLA-identical sibling PBSCT, while invasive candidiasis was rare. Use of steroid prophylaxis and, in particular, the development of moderate-to-severe GvHD post transplant were risk factors for non-Candida IFI. Prophylactic strategies for these infections should thus take into account these risk factors.     

Thrombotic thrombocytopenic purpura after allogeneic stem cell transplantation: a survey of the European Group for Blood and Marrow Transplantation (EBMT)

A survey was carried out among the European Group for Blood and Marrow Transplantation (EBMT) centres to determine the incidence, risk factors, treatment and outcome of thrombotic thrombocytopenic purpura (TTP) following allogeneic haematopoietic stem cell transplantation. TTP was defined as the simultaneous occurrence of red cell fragmentation, laboratory findings of haemolysis, red cell transfusion requirement and de novo or persistent thrombocytopenia caused by consumption, in the absence of disseminated intravascular coagulation. Forty-five centres reported all patients (n = 406) transplanted between July and December 1996. Twenty-three patients developed TTP; the risk of developing TTP was 6.7% at 2 years (95% CI: 4.1% to 9.3%). The median time of onset was 44 d (range 13-319) post transplantation. Significant risk factors for the development of TTP were female gender (P = 0.005) and an unrelated donor (P = 0.046). To treat TTP, cyclosporin administration was discontinued in 10 cases, plasma exchanges were performed in five cases and 12 patients received plasma infusions without plasma exchange. TTP resolved in 13 of the 23 patients (57%). The only factor predictive of resolution of TTP was the absence of nephropathy. Seven patients (30%) were alive at follow-up of 38-45 months from the onset of TTP. Sixteen patients died; the causes were multiple, only three patients had TTP as a central factor. The median time to death was 41 d (range 1-762 d) from the onset of TTP. TTP is a relatively frequent complication of allogeneic stem cell transplantation and it is associated with high mortality, though death is usually caused by multiple factors.     

Thrombotic thrombocytopenic purpura associated with renal failure after autologous transplantation for multiple myeloma successfully treated with rituximab

Thrombotic thrombocytopenic purpura (TTP) is a haematological syndrome characterised by a dramatic onset requiring an urgent treatment with plasma exchange (PE). However, the prognosis is still dismal for PE related complications, a rate of failure and remarkable frequencies of relapse. TTP post transplantation is largely described as an outstanding, unusual complication of allogenic transplantation, but it is rarely mentioned after autologous transplantation. We describe a 62-year-old Caucasian patient who presented with TTP, accompanied by renal failure, after an autologous transplantation for multiple myeloma. PE together with hemodialysis was rapidly initiated but without any benefit. Since empirical administration of Rituximab, anti CD20 monoclonal antibody,was reported to be effective, we administered four courses of Rituximab inducing a complete remission of TTP and subsequently of the renal failure.This response to Rituximab in TTP post transplantation is suggestive of a possible implication of B-lymphocytes in the pathogenesis of TTP and it paves the way for an investigational approach in this settings.     

G-CSF动员同胞供体外周血干细胞的研究

目的：研究粒细胞集落刺激因子（Ｇ－ＣＳＦ）动员异基因外周血干细胞（ＰＢＳＣ）的动力学,分析移植物细胞成分,探讨供者年龄、特别对动员效果的影响。方法：４０个ＨＬＡ相合的同胞供者一日两次皮下注射Ｇ－ＣＳＦ５μｇ／ｋｇ,于第５、６天采集ＰＢＳＣ,所得ＰＢＳＣ以流式细胞仪分析免疫表型。结果：①Ｇ－ＧＳＦ动员过程中供者耐受良好,外周血白细胞和单个核细胞（ＭＮＣ）峰值在第５天;②ＰＢＳＣ含有ＭＮＣ５．８（３．     

Rescue haploidentical peripheral blood stem cell transplantation for engraftment failure: a single‐centre case series

Graft failure affects approximately 5% of allogeneic stem cell transplants, with a poor prognosis. Salvage second allogeneic stem cell transplantation (alloSCT2) is limited by high rates of transplant‐related mortality from infection and graft‐versus‐host disease. We report on five adult patients receiving rescue alloSCT2 using haploidentical peripheral blood stem cells. All patients achieved neutrophil engraftment, two subsequently died from sepsis and disease relapse, respectively. Three patients remain alive up to 2 years post‐transplant. We suggest consideration of haploidentical alloSCT2 for patients with graft failure.     

单个核细胞计数对异基因外周血干细胞移植后造血重建的预测研究

目的探讨单个核细胞(MNC)计数作为造血干(祖)细胞含量的独立指标预测异基因外周血干细胞移植(allo-PBSCT)后造血重建的可行性。方法将暨南大学附属第一医院血液科2000年1月至2008年12月120例allo-PBSCT患者分为MNC组(83例)和CD34+细胞组(37例),MNC组以≥4×108/kg为采集目标,CD34+细胞组以≥4×106/kgCD34+细胞为采集目标。比较两种计数指标对造血重建和供者采集次数的影响,并分析不同MNC剂量对造血重建的影响。结果MNC组受者输入MNC的中位数为6.81×108/kg,CD34+细胞组受者输入CD34+细胞的中位数为5.05×106/kg;两组造血重建率均为100%;两组中性粒细胞植活的中位时间均为移植后第11天(P0.05),血小板植活的中位时间均为移植后第12天(P0.05);两组供者1次采集率分别为100%和37.84%(P0.05);MNC组中HLA全相合与不全相合移植受者中性粒细胞植活的中位时间分别为移植后第11天和移植后第12天(P0.05),血小板植活的中位时间分别为移植后第12天和移植后第14天(P0.05);MNC剂量在(3～5.99)×108/kg递增时,剂量与造血重建呈正相关,而MNC剂量在达到6×108/kg后递增,则并未使植活时间随之进一步缩短。结论MNC计数单独作为造血干(祖)细胞含量的计数指标,不仅能可靠预示allo-PBSCT(包括HLA全相合与不全相合移植)后造血重建,其植活率和植活速度可与CD34+细胞相比拟,而且其供者1次采集率(100%)显著高于后者(37.84%),allo-PBSCT时MNC计数可取代CD34+细胞作为造血干(祖)细胞含量的独立指标。     

CD34~+ CD38~-细胞对异基因造血干细胞移植的影响研究

目的观察CD34+CD38-细胞对异基因造血干细胞移植术后造血重建和移植物抗宿主病(GVHD)的影响。方法分析2004年1月至2009年12月河南省人民医院血液科全相合异基因外周血干细胞造血干细胞移植78例,CD34+、CD34+CD38-细胞输入量与血缘全相合异基因外周血造血干细胞移植术后造血重建及GVHD发生率间的相关性。结果粒细胞、血小板恢复时间与CD34+CD38-细胞输入量呈负相关(r分别为-0.521、-0.448,P<0.01),与CD34+细胞输入量也呈负相关(r分别为-0.405、-0.371,P<0.05)。急性GVHD、慢性GVHD的发生与CD34+、CD34+CD38-、CD3+、CD4+、CD8+细胞输入量无相关性。结论输入高数量的CD34+CD38-细胞有利于移植术后的粒细胞、血小板快速恢复;对于预测术后造血恢复,CD34+CD38-细胞亚群输入量可能优于CD34+细胞总数。     

异基因外周血造血干细胞移植治疗急性白血病(附1例报告)

目的 :探索异基因外周血造血干细胞移植 (allo PBSCT)治疗急性白血病的疗效和移植物抗宿主病(GVHD)的防治。方法 :急性淋巴细胞白血病 (ALL )患者 1例 ,HLA配型完全相合。预处理采用白消安、环磷酰胺(BU/CTX )方案 ;GVHD的预防采用常规环胞菌素A(CsA)加短程甲氨蝶呤 (MTX)加霉酚酸酯 (MMF)方案。治疗慢性GVHD(cGVHD)采用MMF加CsA加硫唑嘌呤 (6 mp)加泼尼松加酞咪哌啶酮 (反应停 ,Thalidomide)。移植有核细胞数 (NC)为 12 .32× 10 8/kg ,CD34+ 细胞为 14 .78× 10 6/kg。结果 :移植 +13d获造血重建 ,同时DNA指纹图提示供者型。移植 +2 2d检测染色体核型为 4 6 ,XX ,10 0 %嵌合。移植 +98d血型由B型转变为A型。移植 +2 10d发生cGVHD ,随访 19个月 ,cGVHD已控制 ,患者现无病生存。结论 :异基因外周血造血干细胞移植可有效治疗急性白血病 ,本例造血重建迅速 ,cGVHD通过治疗后可有效控制     

Effect of high-dose melphalan and peripheral blood stem cell transplantation on renal function in patients with multiple myeloma and renal insufficiency: a case report and review of the literature

 Multiple myeloma with IgG-lambda monoclonal gammopathy and severe renal impairment with light-chain deposit disease was diagnosed in a 51-year-old man. Following conventional therapy with VAD (vincristine, adriamycin, dexamethasone) a partial remission was achieved. Peripheral blood stem cells (PBSC) were then collected following mobilization with cyclophosphamide and recombinant human granulocyte colony-stimulating factor and enriched for CD34-positive cells by immunoaffinity column. Fourteen months after diagnosis high-dose melphalan was given, followed by infusion of CD34-positive PBSC. Aside from mild oral mucositis and trigonitis, high-dose therapy was tolerated well. After he underwent PBSC transplantation his renal function improved, and the patient has been in in continuous complete remission for 1 year. Thus, high-dose chemotherapy can be safely administered to patients with multiple myeloma and severe renal impairment. Our findings confirm previous reports summarized in the current presentation. Received: August 3, 1998 / Accepted: November 2, 1998     

骨髓瘤肾病患者自体外周血干细胞移植治疗临床分析

目的:探讨骨髓瘤肾脏累及患者进行自体外周血干细胞移植(APBSCT)治疗的疗效和安全性。方法:首诊为多发性骨髓瘤(MM)肾病的男性患者4例,年龄35~53岁,进行常规血生化,血、尿免疫蛋白电泳和骨髓穿刺检查,3例行肾脏活组织检查(活检),常规化学治疗(化疗)后均行大剂量化疗(HDT)联合APBSCT。结果:4例患者中IgG型2例,IgD及无分泌型各1例;ⅡA期2例,ⅢA期1例,ⅢB期1例;确诊时均有蛋白尿(1.51～5.70 g),急性肾损伤(AKI)2例,慢性肾脏病(CKD)Ⅱ期、CKDⅤ期各1例。肾穿刺3例中1例弥漫间质炎细胞浸润,1例为轻链沉淀肾病(LCDD),另1例为管型肾病;1例未肾活检,临床推测MM管型肾病可能。移植前常规化疗4~6疗程。3例轻、中度肾功能受累者APBSCT治疗后1例再次发生AKI,但短时间恢复,长期随访尿蛋白基本转阴性,肾功能稳定无进展;1例移植后1年转变为浆细胞白血病死亡,2例MM完全缓解(CR)。1例严重肾功能受累(CKDⅤ期)者移植后因感染性休克死亡。结论:HDT联合APBSCT是治疗MM的有效方法。APBSCT治疗对轻、中度肾功能受累MM肾病患者的肾功能无明显影响,疗效满意。严重肾功能衰竭患者中进行该治疗尚需进一步探讨。