Comparison of allogeneic or autologous hematopoietic stem cell transplant for high-risk peripheral T cell lymphomas

正Objective To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma(PTCL).Methods From July 2007 to July 2014,60 cases of high risk PTCL were analyzed retrospectively.Results All 60 patients were at high risk group(carried with IPI≥3),with a median age of 31     

High-dose therapy with autologous stem cell transplantation in patients with peripheral T cell lymphomas

Peripheral T cell lymphomas (PTCL) have a poorer prognosis after conventional treatment than do high-grade B cell lymphomas. The place for high-dose therapy (HDT) with autologous stem cell support in these patients is still not clear. Forty patients, 10 women and 30 men, median age 41.5 years (range 16-61) with PTCL were treated with HDT and autologous stem cell support at The Norwegian Radium Hospital, Oslo, Norway and The University Hospital, Uppsala, Sweden, between February 1990 and September 1999. The histologic subtypes were: PTCL unspecified, 20 patients; intestinal, two patients; angioimmunoblastic (AILD), two patients; angiocentric, two patients and anaplastic large cell lymphoma (ALCL), 14 patients. All patients had chemosensitive disease and had received anthracycline-containing regimens prior to transplantation. At the time of HDT, 17 patients were in first PR or CR and 23 were in second or third PR or CR. Conditioning regimens were BEAM in 15 patients, BEAC in 14 patients, cyclophosphamide and total body irradiation (TBI) in eight patients, BEAC, without etoposide and TBI in one patient and mitoxantrone and melphalan in two patients. There were three (7.5%) treatment-related deaths. The estimated overall survival (OS) at 3 years was 58%, the event-free survival (EFS) 48% and the relapse-free survival (RFS) 56%, with a median follow-up of 36 months (range 7-100) for surviving patients. The patients with ALCL tended to have a better prognosis compared to those with other PTCL subtypes, OS 79% vs 44%, respectively. In conclusion, patients with chemosensitive PTCL who are failing to achieve CR with first-line chemotherapy or are in relapse can successfully be treated with HDT and autologous stem cell support.     

Radioimmunotherapy and autologous stem cell transplantation for the treatment of B-cell lymphomas

Relapse continues to be the primary cause of treatment failure in patients with non-Hodgkin's lymphomas (NHL) undergoing high-dose therapy and autologous stem cell transplantation. The anti-CD20 radioimmunoconjugates, Y-90 ibritumomab tiuxetan (Zevalin; Biogen Idec, Inc., Cambridge, MA, USA) and I-131 tositumomab (Bexxar; Corixa, Seattle, WA; and Glaxo Smith Kline; Philadelphia, PA, USA) have been associated with high response rates, durable remissions and limited toxicity apart from myelosuppression, making them ideal candidates for use in autotransplantation. Tested first as single agents in relapsed patients with indolent and transformed NHL, and then at much higher doses with stem cell support, these agents have now been combined with high-dose chemotherapy prior to autologous stem cell transplant. Radioimmunoconjugates have been used to replace total body irradiation (TBI) in some studies and to augment standard chemotherapy regimens in others. Thus far the results are promising, with combinations of radioimmunoconjugates and chemotherapy producing long-lasting responses in high-risk patients with no more toxicity than that caused by standard conditioning regimens. These results are notable in light of the fact that the dose of radiation delivered to the tumor is 10-fold higher than the dose achievable with TBI. Whether this increase in radiation dose to the targeted lymphoma translates into more durable remissions and an improvement in overall survival requires further investigation.     

Long-term outcomes in children with high-risk neuroblastoma treated with autologous stem cell transplantation

We retrospectively analysed the outcomes of children transplanted for high-risk neuroblastoma (NB) at a single institution predominantly transplanted with total body irradiation and chemotherapy. The aims of this study were to determine the prognostic impact of clinical and biological features and to document long-term health outcomes. Forty patients were transplanted with a single unpurged autograft. Fourteen patients died from disease progression and two from late complications of treatment. Twenty-three patients are alive at a median of 4.6 years from diagnosis. Kaplan-Meier estimates of overall survival at 2, 5 and 10 years are 76+/-7.0, 60.2+/-8.4 and 54.7+/-9.3% following transplant. Response to induction therapy was significantly associated with survival (P<0.01). Long-term complications included growth (100%) and pubertal failure (83%), hearing impairment (73%), orthopaedic complications (63%), renal impairment (47%) and thyroid abnormalities (36%). Intrinsic and acquired resistance to chemotherapy remains the major obstacle to improving outcomes in high-risk NB. Although patients with chemo-sensitive disease are less likely to experience a relapse, substantial therapy-related toxicities result in poor long-term health outcomes for survivors.     

Outpatient reduced-intensity allogeneic stem cell transplantation for patients with refractory or relapsed lymphomas compared with autologous stem cell transplantation using a simplified method

The effectiveness of reduced-intensity conditioning allogeneic stem cell transplantation (allo- RIC) compared with high-dose chemotherapy followed by autologous stem cell transplantation (auto-SCT) in Hodgkin’s disease (HD) and in non-Hodgkin’s lymphoma (NHL) patients remains poorly defined. The purpose of the study was to demonstrate the usefulness of auto-SCT or allo-SCT, employing a RIC regimen in refractory or relapsed NHL or HD patients. We analyzed the outcome of 71 patients with advanced disease. Twenty-three NHL and 14 HD patients received an allo-RIC using fludarabine, cyclophosphamide, and low-dose busulfan as the conditioning regimen. Sixteen NHL and 18 HD patients received auto-SCT using cyclophosphamide and etoposide as conditioning regimen. All hematopoietic stem cells products were not cryopreserved and the majority of grafts were done on an outpatient basis, including conditioning and post-stem cell infusion care (auto-SCT, 62% and allo-RIC procedure, 91%). The median OS was 45.5 months for the allo-RIC recipients and 53.3 months for auto-SCT recipients. Acute/chronic GVHD incidence in NHL and HL groups was 38%/31% and 14%/7%, respectively. We found no significant difference in overall survival between allo-RIC group and auto-SCT group for NHL patients (P = 0.43) but better OS was observed for auto-SCT group than for allo-SCT group in HL patients (P < 0.001). The relapse rate was higher in autografted patients, both in NHL and HD. Both auto-SCT and allo-RIC appear to be valid treatments for poor-risk patients with relapsed or refractory lymphoma who could not otherwise be cured with conventional salvage regimens.     

Autologous stem cell transplantation for HIV-associated lymphoma.

Is peripheral stem cell mobilization followed by autologous stem cell transplantation (ASCT) feasible in patients with human immunodeficiency virus (HIV)- associated lymphoma (HIV-L)? Studies have demonstrated that, in the HIV- negative (HIV(-)) setting, ASCT may improve lymphoma-free survival in high-risk non-Hodgkin lymphoma (NHL) or relapsed Hodgkin disease (HD) and NHL. Given the poor prognosis of HIV-L with conventional chemotherapy, this dose-intensive approach was explored. Nine patients with HIV-HD or NHL mobilized a median of 10.6 x 10(6) CD34(+) cells/kg and engrafted after ASCT. CD4 counts recovered to pretransplantation levels and HIV viral loads were controlled in patients compliant with antiretroviral therapy. Seven of 9 patients remain in remission from their lymphoma at a median of 19 months after transplantation. Thus, patients with HIV-L on antiretroviral therapy can engraft following ASCT. Prolonged lymphoma remissions, without significant compromise of immune function, can be seen, suggesting that ASCT can be used in selected patients with HIV-L.     

Long-term clinical and molecular remissions in patients with mantle cell lymphoma following high-dose therapy and autologous stem cell transplantation

Long-term clinical and molecular remissions in patients with mantle cell lymphoma (MCL) following high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) have been evaluated in only a few studies. Thirty-six patients with MCL received ASCT in our institution (27 patients undergoing first-line therapy, 8 patients undergoing second-line therapy, and 1 patient undergoing third-line therapy). In the case of long-term remission (≥5 years; n?=?8), peripheral blood was tested for minimal residual disease (MRD) by t(11; 14) polymerase chain reaction (PCR) and immunoglobulin heavy-chain (IGH) PCR at the last follow-up. Ten-year overall survival (OS), progression-free survival (PFS), and freedom from progression (FFP) after first-line ASCT were 42 %, 43 %, and 54 %; after second-line ASCT, these were all 0 %. Four-year OS, PFS, and FFP for the first-line cohort were 75 %, 48 %, and 61 %, respectively. Four-year OS, PFS, and FFP after second-line ASCT were 55 %, 30 %, and 30 %, respectively. Treatment-related mortality (3 months after ASCT) was 0 %. The only prognostic factor for OS, PFS, and FFP was treatment line (p?=?0.011, p?=?0.046, and p?=?0.023, respectively). No relapses occurred after 5 years following ASCT. So far, eight patients developed sustained long-term clinical and molecular complete remissions of up to 14.6 years following ASCT in the first treatment line. Sustained long-term clinical and molecular remissions can be achieved following ASCT in the first treatment line and apparently less frequent in the second treatment line.     

High-dose chemotherapy and autologous peripheral blood stem cell transplantation in high-risk multiple myeloma

We compared the effect of high-dose therapy together with autologous peripheral blood stem cell transplantation (autoPBSCT) in 60 patients with multiple myeloma (MM) with 90 patients who underwent conventional chemotherapy. We scored the prognostic factors according to our reported classification system that includes measurements of serum albumin, serum beta-2-microglobulin, and morphology of myeloma cells selected by multivariate analysis. We separated the patients into three risk groups at stratification level I (low, intermediate and high) and into two risk groups at stratification level II (low and high). AutoPBSCT tended to be as effective for high, as for low-risk patients in level I, and was obviously as helpful for high, as for low-risk patients in stratification II. In conclusion, high-risk patients with MM should be treated with high-dose therapy accompanied with autoPBSCT like low-risk patients.     

HIV-associated lymphoma successfully treated with peripheral blood stem cell transplantation

OBJECTIVE: To evaluate feasibility, safety, and efficacy of peripheral blood stem cell collection (PBSCC) and autologous stem cell transplantation (ASCT), to treat patients diagnosed of high-risk or relapsed HIV-associated lymphoma (HIV+ Ly), responding to highly active antiretroviral therapy (HAART). METHODS: Prospective and multicentric study in patients with high-risk or relapsed chemosensitive HIV+ Ly, candidate for consolidation with ASCT. Eligibility criteria were similar to those of HIV- lymphoma. HAART was aimed to be maintained during the procedure. RESULTS: Fourteen patients were admitted. Adequate PBSCC was obtained from all patients (median CD34+ cells was 4.7 x 10(6)/kg). Three patients died before ASCT; two had disease progression and one died from VHC-liver failure. Eleven transplanted patients showed neutrophil engraftment after a median time of 16 days (range, 9-33 days), and nine patients showed platelet engraftment after a median time of 20 days (range, 11-36 days). CD4+ cell counts and HIV viral load (VL) were appropriately preserved along the procedure. No patients died from treatment-related complications. One patient died from lymphoma progression (day +19), and another died in complete remission (CR) with undetectable VL, 15 months after transplant, due to infection. One patient relapsed at 32 months after ASCT. The remaining eight patients are alive in CR with an event-free survival of 65% and a median follow-up of 30 months after ASCT (range, 7-36 months). CONCLUSIONS: These results show that feasibility, safety, and efficacy of PBSCC and ASCT in HIV+ Ly patients responding to HAART are similar to those observed in the HIV- lymphoma setting.     

Efficiency of in vivo purging with autologous stem cell transplantation and monoclonal antibody in B-cell lymphomas

Elimination of tumor cells from hematopoietic stem cell products is a major goal of bone marow-suported high-dose cancer chemotherapy. In patients (pts) with low-grade lymphoma Gianni et al (2000) assessed the ability of Rituximab, given in combination with high-dose chemotherapy, to eradicate PCR-detectable disease and enable the harvesting of large amounts of uncontaminated circulating progenitor cells. Our study was conducted in 27 consecutive pts with untreated bcl2 positive NHL (follicular lymphoma--7, chronic lymphocytic leukemia--13 and NHL in leukemic phase--7), 14 pts received Rituximab. Patients received 4 courses of standard-dose chemotherapy (CHOP or FLU-CY), followed by one course of high-dose cyclophosphamid plus G-CSF. Patients allocated to Rituximab received i.v. infusions of 375 mg/m2 48 hours before stem cell collection and in 3 weekly doses after transplantation (R-CHT). Clinical response after transplantation was evaluated in 26 pts who completed the treatment. The complete response rate was in 100% in the Rituximab group (PCR negative in 79%) versus 50% of controls (p<0.01). Yield of purged CD34+ cells was with median 5.23x10(6)/kg in CHT and 8.76x10(6)/kg in R-CHT pts. Toxicity in the both arms was acceptated (no difference). No significant difference was observed between CHT and R-CHT group in the mean number of days spent with neutropenia and trombocytopenia. After a follow-up of 31 months, no patient relapsed. Aside from providing PCR-negative harvests, the chemoimmunotherapy treatment produced complete clinical (100%) and molecular remission in 79% of evaluable pts. We showed that Rituximab in combination with effective high-dose anti- lymphoma chemotherapy, allowed the harvesting of large amounts of tumor free progenitor cells in evaluable pts.     

Idiopathic pneumonia syndrome after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for high-risk breast cancer

Our aim was to describe the incidence, clinical course, and risk factors for idiopathic pneumonia syndrome (IPS) after high-dose chemotherapy with cyclophosphamide, carmustine, and thiotepa followed by autologous stem cell transplantation for high-risk breast cancer. Charts for patients who underwent high-dose chemotherapy for high-risk breast cancer at a single center from 1992 to 2000 were retrospectively reviewed, and potential risk factors for development of IPS were sought with the log-rank test. Of 164 patients reviewed, 20 developed IPS at a median onset of 87 days after the transplant (range, 2-257 days). The actuarial incidence of IPS in the first 100 days after the transplant was 8%, and 95% of patients developed symptoms within the first 6 months after transplant. Patient age, smoking status, breast cancer stage at diagnosis, and pretransplant lung function did not predict development of IPS. Three patients died of progressive pulmonary failure and the IPS resolved in the other 17. We concluded that IPS is an important cause of morbidity and mortality in patients with high-risk breast cancer undergoing high-dose chemotherapy. Given the absence of predictive factors, any pulmonary symptoms appearing in the first year after the transplant should be evaluated carefully.     

Overview of autologous stem cell transplantation

There has been a dramatic increase in the number of autologous peripheral blood stem cell transplants over the last decade. Faster recovery of cell counts, lesser transplant morbidity, shorter hospital stay and reduced cost compared with marrow autografts have been the main advantages of autologous peripheral blood cell over marrow transplants. In this paper we attempt to review the advances in the biology and mobilization of stem cells, and focus on clinical results of autologous peripheral stem cell and marrow transplants for disease specific sites such as breast cancer, myeloma, autoimmune diseases, germ cell tumors, the acute and chronic leukemias, the non-Hodgkin's lymphomas and Hodgkin's disease. We also discuss transplant related complications, gene therapy and the different methods of purging. This review was intended for autologous peripheral stem cell transplants, however, unavoidably, it also discusses autologous marrow transplantation and aspects common to both procedures.     

Pegfilgrastim compared with filgrastim after autologous peripheral blood stem cell transplantation in patients with solid tumours and lymphomas

To evaluate the safety and efficacy of pegfilgrastim administered as haematological support after autologous peripheral blood stem cell transplantation, we compared 44 patients with solid tumours and lymphomas receiving a 6-mg single dose of pegfilgrastim on day +5 after transplantation to a historical control group of 25 patients receiving filgrastim 5 μg kg⁻¹ day⁻¹ starting on day +5. There were no significant differences in haematological recovery nor in the incidence and duration of neutropenic fever. Median duration of grade 4 neutropenia in the pegfilgrastim and filgrastim group was similar. The incidence of grade III–IV mucositis was lower in pegfilgrastim than in filgrastim group due to the significant difference observed among the patients with solid tumours (p = 0.00). The only adverse event considered to be cytokine related was mild to moderate bone pain occurring during haematological recovery. According to the present study design and taking into account the current prices in our institution, the cost of the two drugs was similar in both treatment groups. In conclusion, a single injection of pegfilgrastim administered at day +5 post-transplantation shows comparable safety and efficacy profiles to daily injections of filgrastim and may be cost effective. Alberto Ballestrero and Davide Boy contributed equally to this article.     

Autologous stem cell transplantation in patients with high-risk plasmacytoma

Although autologous stem cell transplantation (ASCT) is considered standard treatment in patients with multiple myeloma (MM), limited experience is available on this approach in patients with plasmacytoma (PC). Twelve patients with high-risk PC received ASCT in Finland 1994-2002. There were nine males and three females with a median age of 50 yr (32-64). Ten patients had a PC of bone, whereas two patients had extramedullary PCs. The median time from the diagnosis to ASCT was 9 months (5-100). At the time of ASCT six patients were in first complete remission (CR) or partial remission (PR), in four patients the disease was refractory to the first line therapy and two patients had relapsed. High-dose therapy consisted of melphalan (MEL)200 (n = 7), MEL200 x 2 (n = 3) or total body irradiation (TBI)-MEL140 (n = 2). No transplant-related deaths occurred. After ASCT eight patients (67%) were in CR, one patient in very good PR and one patient in PR; two patients were non-responders. With a median follow-up of 48 months from ASCT, 11 patients (92%) are alive. Six patients (50%) have relapsed or progressed 3-81 months from ASCT. ASCT is feasible in this patient population resulting in promising overall survival. A randomised trial is needed to assess the real value of ASCT when compared with other treatment options in patients with high-risk PC.     

Heart transplantation for cardiac light chain amyloidosis with subsequent autologous stem cell transplantation

Our report describes a case of 57-year-old man with manifest heart failure on the basis of cardiac amyloidosis, which was detected by endomyocardial biopsy. Due to the heart failure, the patient was unable to undergo myeloablative therapy. We changed our previous decision for conservative therapy of heart failure and the patient underwent heart transplantation. Autologous stem cell transplantation was performed 6 months later. After the successful stem cell transplantation, the serum free light chain lambda levels promptly decreased. One year later, their levels started again to increase. Chemotherapy was therefore initiated. The patient has now completed the seventh cycle of chemotherapy in good condition. The graft function is normal and the latest endomyocardial biopsy revealed no amyloid.     

异基因造血干细胞移植治疗高危恶性血液病

目的 分析HLA配型相合同胞供者异基因造血干细胞移植（allo-HSCT）治疗高危恶性血液病的疗效及影响疗效的相关因素。方法 回顾性分析90例有高危因素的恶性血液病患者,其中急性髓细胞白血病（AML）43例,急性淋巴细胞性白血病（ALL）28例,急性混合细胞性白血病（AHL）2例;移植前处于第1次完全缓解期（CR1）11例,均为Ph染色体阳性,第二次及以上CR期23例,未缓解／复发39例;骨髓增生异常综合征（MDS）-难治性贫血伴原始细胞增多或难治性贫血伴原始细胞增多一转化型17例。预处理方案采用全身照射加环磷酰胺（CY／TBI）方案11例,白消安加环磷酰胺方案79例。干细胞来源包括骨髓移植（BMT）27例,外周血造血干细胞移植（PBSCT）30例,BMT＋PBSCT33例;移植物抗宿主病（GVHD）预防采用经典环孢素A加短程甲氨蝶呤（MTX）。平均随访时间为15个月。结果 至随访终点,62．2％（56／90）存活,55．5％（50／90）无病存活,31．1％（28／90）复发。HSCT后预计4年累积总体生存率（OS）为45．5％,无病生存率（DFS）为34．9％。移植前处于CR、未缓解／复发和MDS患者HSCT后4年的累积0s分别为54．0％、28．2％和70．1％（P=0．027）。发生0～Ⅰ和Ⅱ～Ⅳ度GVHD的患者HSCT后的4年OS分别为57．6％和26．7％（P=0．015）,而患者性别、年龄、移植前有无脑膜白血病、预处理方案、干细胞来源均不是OS,DFS及复发的影响因素。多因素分析表明,移植前处于CR期者长期生存率明显提高,而ALL长期生存率明显低于AML／MDS。结论 对有高危因素的血液系统恶性肿瘤患者,选择allo—HSCT可使部分患者延长无病生存乃至根治。移植前处于CR期者长期生存率明显提高,ALL复发率明显高于AML／MDS。对于急性白血病挽救性治疗争取在取得CR后移植;对于MDS患者一经诊断,无需化疗,可尽早移植。