Ten‐year survival after autologous stem cell transplantation for immunoglobulin light chain amyloidosis

BACKGROUND:

The current study was conducted to determine characteristics distinguishing the 10‐year survivor group in patients with systemic immunoglobulin light chain (AL) amyloidosis who underwent autologous stem cell transplantation (SCT).

METHODS:

The study group included all 74 patients with AL amyloidosis who underwent high‐dose melphalan treatment supported by autologous SCT since the beginning of the Mayo Clinic's SCT program until prior to August 2001.

RESULTS:

A total of 32 patients (43%) patients survived for > 10 years. Statistically significant baseline differences in the 10‐year survivor group included: 1) the number of organs involved; 2) septal thickness; 3) total cholesterol; and 4) urine total protein. The number of organs involved was the only predictor found on multivariable analysis. Depth of the response to therapy, as measured by the lowest posttransplantation serum free light chain level, was found to be the most significant indicator of durability of response.

CONCLUSIONS:

Autologous SCT can offer durable benefit for patients with AL amyloidosis. The number of organs involved offers the greatest pretreatment prognostic value, whereas the lowest posttransplantation serum free light chain level offers the best posttreatment prognostic value. Cancer 2012. © 2012 American Cancer Society.     

Three patients with primary AL amyloidosis treated by high-dose melphalan with autologous peripheral blood stem cell transplantation

We present three long-term survivors treated with high-dose melphalan with autologous peripheral blood stem cell transplantation(auto PBSCT)for primary AL amyloidosis. Because melphalan toxicity is dose-related, patient age and the extent of organ involvement are very important factors for the success of high-dose melphalan treatment with PBSCT. The patients were therefore given high-dose melphalan using the risk-adapted approach to melphalan dosing. They received 3 courses of a vincristine, doxorubicin and dexamethasone(VAD)regimen, along with high-dose melphalan(100-200mg/m2)with auto PBSCT. There were no serious complications or transplantation-related mortalities. Patients survived for an average of 68 months(22-100 months)in partial response. A risk-adapted approach to melphalan dosing with PBSCT is an effective treatment in patients with primary AL amyloidosis.     

Engraftment and outcomes following autologous stem cell transplantation in Hodgkin lymphoma patients mobilized with plerixafor

Plerixafor has been used to improve peripheral blood stem cell (PBSC) mobilization in multiple myeloma, non‐Hodgkin lymphoma, and very recently in Hodgkin lymphoma (HL) patients. Because prior studies have suggested that mobilization with plerixafor affects the composition of mobilized cells, there are concerns that this may in turn adversely impact the immune reconstitution and longer term outcomes of transplanted patients. However, data on the engraftment characteristics and long‐term post‐transplant outcomes in patients transplanted with plerixafor‐mobilized PBSCs are lacking. This retrospective study examined the post‐transplant outcomes of 105 consecutive adult HL patients, and compared the post‐transplant outcomes of 21 patients who received plerixafor in addition to G‐CSF ± chemotherapy because of poor mobilization with those of 84 patients who mobilized well without plerixafor. Despite collecting significantly lower CD34+ cell doses (median of 3.41 vs. 6.05 × 10⁶/kg, p < 0.0001) than control patients and requiring more collection days, plerixafor‐mobilized patients showed comparable early engraftment characteristics, except for slightly delayed neutrophil engraftment (median: 11 vs.10 days, p = 0.002) and lower median neutrophil counts (2.1 vs. 2.6 × 10⁹/L, p = 0.04) at one month after transplant. No significant differences were observed in longer term post‐transplant outcomes, including cell counts at 3, 6, and 12 months, RBC and platelet transfusion support during the first 120 days, relapse incidence, overall and progression‐free survival rates up to two years post transplant. The use of plerixafor not only enabled poorly mobilizing HL patients to collect enough PBSCs to proceed to ASCT, but also to have similar post‐transplant outcomes compared to patients who mobilized well with conventional regimens. Copyright © 2016 John Wiley & Sons, Ltd.     

Involved field radiation post autologous stem cell transplantation in lymphoma patients is associated with major haematological toxicities

Irradiation is known to cause temporary to permanent marrow aplasia in cancer patients when administered as a sole therapy or in combination with chemotherapy. Until now, no studies have been carried out evaluating the haematological toxicities of involved field radiation administered post autologous stem cell transplantation (ASCT). We assessed bone marrow (BM) toxicity in 93 patients who received involved field radiation post ASCT (non-Hodgkin’s lymphoma 21, Hodgkin’s disease 7, breast cancer 15, and other solid tumours 50. Severe BM toxicity, with grade IV neutropenia, and/or thrombocytopenia, and/or anaemia necessitating interruption of radiotherapy for more than a week, was observed in 11 patients (malignant iymphoma-8 of which 7 were NHL, and 1 HD, breast cancer-1, Wilm’s tumour-1, Ewing’s sarcoma-1). Patients with malignant lymphoma were at higher risk of developing post ASCT radiation-induced cytopenias than patients with breast cancer or solid tumours, 28% vs 4.5%, respectively (P<0.05). Of the 11 patients, 7 developed bacterial sepsis and 10 were hospitalised. The radiation-induced cytopenia patients necessitated platelets and red blood cell transfusions, interrupting the course of irradiation. Of the patients suffering from non-Hodgkin’s lymphoma, 8/14 (57%) of those who received conventional courses of radiotherapy relapsed compared to 6/7 (86%) of those who received interrupted radiotherapy (P < 0.05). The most appropriate timing for radiation in malignant lymphoma patients who are scheduled for ASCT, as well as the protective role of haematopoietic growth factors like erythropoietin and Granulocyte (G) or Granulocyte-Monocyte (GM), colony stimulating factors (CSF) and others, are discussed. Keywords: ABMT; radiation; neutropenia; thrombocytopenia; sepsis; transfusion; relapse; haematopoietic growth factors (HGF)     

Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation

BACKGROUND: Mylotarg (Wyeth-Ayerst Laboratories, St. Davids, PA) is the brand name for a calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab ozogamicin, CMA-676) and has been approved recently for the treatment of a subset of elderly patients who have relapsed acute myeloid leukemia (AML). Mylotarg is associated with an incidence of approximately 20% Grade 3 or 4 hyperbilirubinemia and liver transaminitis in this patient population. Hepatic venoocclusive disease (VOD) has been reported in patients who have undergone stem cell transplantation (SCT) after Mylotarg therapy. Outside of the SCT setting, VOD has been associated very rarely with cytotoxic therapy. METHODS: The authors assessed the incidence of VOD in 119 patients who were receiving Mylotarg-containing non-SCT regimens. VOD was diagnosed through the use of standard Seattle and Baltimore criteria. RESULTS: A cohort of 119 (61 previously untreated, 58 with relapsed disease) patients with AML (92 patients), advanced myelodysplastic syndrome (25 patients), or chronic myeloid leukemia in blast phase (2 patients), received Mylotarg-based regimens. Fourteen (12%) developed VOD. The diagnosis of VOD was supported by histology in 2 patients and radiologic studies in a further 10 patients. Five (36%) of 14 patients with VOD had received no prior antileukemic cytotoxic therapy, including 2 patients who received single-agent Mylotarg therapy. CONCLUSIONS: Mylotarg was shown to be associated with the development of potentially fatal VOD in patients with leukemia who had not received SCT. VOD occurred when Mylotarg was used either as a single agent or when it was given with other cytotoxic agents. VOD occurred in Mylotarg-treated patients who had received no prior cytotoxic therapy. The current study concluded that risk factors for VOD should be assessed when considering Mylotarg therapy, and that attempts to avoid and treat VOD are warranted in patients who receive Mylotarg therapy.     

自体干细胞移植支持下的大剂量化疗一线治疗恶性淋巴瘤

背景与目的:目前自体干细胞移植(autologous stem cell transplantation,ASCT)支持下的大剂量化疗(high-dose chemotherapy,HDC)已成为复发或难治性恶性淋巴瘤(malignant lymphoma,ML)的标准治疗方法,但是对于一些选择的ML是否可作为一线治疗方案目前尚不明确.本文旨在通过回顾性分析探讨HDC/ASCT作为一线方案治疗ML的疗效.方法:自2000年9月至2007年6月, 连续收治28例ML患者,中位年龄32岁(8～60岁),其中男性17例,女性11例.组织学类型包括24例非霍奇金淋巴瘤,4例霍奇金淋巴瘤.自体外周血干细胞动员采用化疗药物联合重组人粒细胞集落刺激因子方案.HDC方案采用BEAC(BCNU、CTX、Ara-C 、VP-16)方案.随访日期自干细胞回输之日期开始,末次随访日期为2007年7月30日.结果:28例患者均移植成功,重建造血功能.移植前CR 14例,PR 14例,移植后CR 22例,PR 6例.随访截止日期为2007年7月30日,中位随访时间为28个月(1.5～82个月),移植后4例病情进展,其中2例死亡,3年生存率及无进展生存率分别为89%和76%.大剂量化疗期间不良反应均可耐受,无移植相关死亡.结论:HDC/ASCT作为一线方案治疗ML是安全、可行及有效的治疗方法.     

Chemotherapy with rituximab followed by high-dose therapy and autologous stem cell transplantation in patients with mantle cell lymphoma

BACKGROUND: The authors evaluated the efficacy of chemotherapy combined with rituximab followed by high-dose therapy (HDT) plus autologous stem cell transplantation in patients with mantle cell lymphoma (MCL). METHODS: This was a retrospective analysis of 34 patients who were treated in 2 departments of hematology, including 29 patients (85%) who received first-line treatment. Rituximab was administered as 4 injections just before harvest in 25 patients (73%) or simultaneously with chemotherapy in 9 patients (27%). HDT included total body irradiation in 26 patients (77%). RESULTS: After induction therapy, all patients except one reached a response: There were 14 (41%) complete responses (CR) and 19 (56%) partial responses (PR). Stem cell harvest was successful in all patients but 2, with a median number of 5.9 CD34-positive cells per 10(6)/kg. Three months after transplantation, 24 patients (71%) were in CR, and 7 patients (21%) were in PR. At 3 years from the day of transplantation, the estimated overall survival was 87%. With a median follow-up at 2.6 years, the estimated median time to disease progression was 3.4 years. Rituximab treatment before harvest did not delay hematopoietic reconstitution: The median time it took patients to recover absolute neutrophil count to > 0.5 G/L was 10 days. CONCLUSIONS: Chemotherapy combined with rituximab followed by HDT improved the overall survival and progression-free survival in patients MCL without adding toxicities.     

Autologous stem cell transplantation in patients with primary amyloidosis: a nation-wide survey

Due to poor prognosis with conventional therapy, high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is considered for treatment in patients with primary amyloidosis (AL). Only single centre series are available on the feasibility and efficacy of this approach. Altogether 20 AL patients (11 males, 9 females, median age 54 years) were included in HDT protocols in 5 Finnish transplant centres between 1997 and 2003. Twelve patients were mobilized with granulocyte colony-stimulating factor (G-CSF) alone and 8 patients with a combination of cyclophosphamide and G-CSF. Sixteen patients (80%) went on to high-dose melphalan. Early transplant-related mortality was 25%. Nine out of 11 evaluable patients showed improvement or stabilization of AL. The overall survival of the transplanted patients is 69% (median follow-up 13 months). After a median follow-up of 26 months for the living patients, only 2 patients (18%) have shown progression of AL. This retrospective nation-wide analysis shows that HDT with ASCT leads to improvement or stabilization of AL in the majority of the patients who survive the immediate posttransplant period. A randomized multicentre trial is needed to show whether ASCT is superior to conventional therapy in patients with AL.     

High-dose therapy and autologous stem cell transplantation in Korean patients with aggressive T/NK-cell lymphoma

The proportion of aggressive T/NK-cell lymphoma in Korea is larger than in the West, and it shows a lower response to conventional chemotherapy and poorer survival than diffuse large B-cell lymphoma. This study was undertaken to evaluate the response rate and survival and to document the prognostic factors in patients with T/NK-cell lymphoma who have undergone high-dose therapy (HDT). Eligibility for the study was a mature T/NK-cell lymphoma with initially poor risk (as high or high intermediate risk on age-adjusted International Prognostic Index) or relapsed cases. Twenty-eight patients from 6 centers were reviewed retrospectively. The M : F ratio was 20:8, and median age was 36 years (range 16--60 years). Twelve patients had unspecified peripheral T-cell lymphomas, 7 anaplastic large-cell lymphomas, 6 nasal T/NK-cell lymphomas, and 3 angioimmunoblastic T-cell lymphomas. Disease status at transplant were initially poor risk in 15, chemosensitive relapse in 8 and chemo-resistant relapse in 5 patients, respectively. A complete response (CR) after HDT comprised 20 patients, including 16 with continued CR. Absolute neutrophil count ( > 500/microl) recovered at a median 11 days after autologous stem cell transplantation in 26 patients. Two therapy-related mortalities occurred. Estimated 3-year event-free survival and overall survival (OS) (+/- SE) were 24+/- 9 and 42+/- 10 months, respectively. Only CR status after HDT influenced OS (P=0.000). Therefore, an initial approach with effective induction and HDT may result in a better outcome in T/NK-cell lymphoma.     

自体造血干细胞移植治疗恶性淋巴瘤15例临床分析

目的:评价自体造血干细胞移植(AHSCT)治疗恶性淋巴瘤患者的疗效。方法:采用AHSCT治疗恶性淋巴瘤患者15例,其中霍奇金淋巴瘤患者3例(均为复发病例),非霍奇金淋巴瘤患者12例(Ⅲ、Ⅳ期或复发病例,IPI评分2-4分)。采集外周血造血干细胞前均经化疗及动员剂动员(CHOP方案9例,CHOP+MTX 3例,CEP、大剂量MTX、单用G-CSF各1例)。预处理方案为联合化疗10例(BEAC、CBV方案为主),联合化疗加放射治疗5例(TBI、TLI各1例,提前局部照射3例)。结果:移植后白细胞≥1.0×109/L的中位时间为10(9-13)天,血小板≥50×109/L的中位时间为14(11-17)天。随访时间为1-110.5个月。中位生存时间为43(1-110.5个月)个月,3年总生存率(OS)为66.7%。结论:AHSCT是一种治疗复发难治恶性淋巴瘤的安全有效的方法。     

自体造血干细胞移植治疗中、高度恶性淋巴瘤

背景与目的:自体造血干细胞移植(autologoushemotopoieticstemcelltransplantation,ASCT)支持下的大剂量化疗目前已成为治疗对化疗敏感的淋巴瘤最有效的手段之一。本研究评价自体造血干细胞移植支持下的大剂量化疗加放疗治疗预后差的中、高度恶性淋巴瘤的疗效。方法:1995年11月～2001年5月收集到的13例病例中,非霍奇金淋巴瘤(non-Hodgkinslymphoma,NHL)11例,复发霍奇金淋巴瘤(Hodgkinsdisease,HD)2例。移植前首次完全缓解(firstcompleteremission,CR1)8例,第二次完全缓解(secondcompleteremission,CR2)4例,第二次部分缓解(secondpartialremission,PR2)1例。预处理方案:单纯化疗4例;化疗加受累区放疗6例;全身放疗加化疗3例。2例采用自体骨髓移植,11例行自体外周血干细胞移植。结果:本组病例回输单核细胞(mono-nuclearcell,MNC)和粒-巨细胞系祖细胞(granulocyte-macrophagecolony-formingcells,CFU-GM)的均数(范围)分别为2.55(2.07～3.31)×109/L和1.43(0.6～2.36)×109/L。随访到2001年10月,所有患者造血功能都获得重建。白细胞恢复到≥1.0×109/L和血小板>50×109/L的中位时间(范围)分别为6(7～35)天和8(6～32)天。CR持续时间为4～57个月,中位时间为16个月,1年生存率76.9%,3年生存率46.2%。结论:自体造     

Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis.

PURPOSE: Absolute lymphocyte count recovery at day 15 (ALC-15) post-autologous stem cell transplantation (ASCT) is a powerful prognostic indicator for survival for multiple hematologic malignancies and metastatic breast cancer. The relationship of ALC-15 with clinical outcomes in primary systemic amyloidosis is unknown. EXPERIMENTAL DESIGN: We evaluated 145 consecutive patients with primary systemic amyloidosis who underwent ASCT at the Mayo Clinic from 1996 to 2003. The ALC-15 threshold was set at 500 cells/microL based on our previous observations. RESULTS: The median patient follow-up was 22 months (range, 3-87 months). Higher hematologic complete response was observed in patients with an ALC-15 > or = 500 cells/microL compared with patients with an ALC-15 < 500 cells/microL (41% versus 21%, P < 0.0008, respectively). The median overall survival and progression-free survival times were significantly better for the 59 patients that achieved an ALC-15 > or = 500 cells/microL compared with 86 patients with ALC-15 < 500 cells/microL (not reached versus 53 months, P < 0.0003 and not reached versus 27 months, P < 0.0001, respectively). Multivariate analysis showed ALC-15 to be an independent prognostic factor for overall survival and progression-free survival. CONCLUSIONS: ALC-15 > or = 500 cells/microL is associated with significantly improved clinical outcomes following ASCT in patients with primary systemic amyloidosis.     

Comparison between autologous and allogeneic stem cell transplantation as salvage therapy for multiple myeloma relapsing/progressing after autologous stem cell transplantation

Allogeneic stem cell transplantation (allo‐SCT) offers a clinical option to young patients with multiple myeloma (MM) relapsing/progressing after autologous SCT (ASCT); however, this claim remains debatable. Thus, in this retrospective study, we analyzed 526 patients with MM who underwent SCT for MM relapsing/progressing after the prior ASCT using the registry data of the Japan Society for Hematopoietic Cell Transplantation (2001‐2015) and compared overall survival (OS) between allo‐SCT (n = 192) and autologous stem cell retransplantation groups (ReASCT; n = 334) based on risk factor points. Significant adverse factors for OS in all patients were (1) male sex, (2) less than partial response to SCT, (3) performance status of 2 to 4, and (4) short duration from the prior ASCT. We scored factor 2 as 1 point, factor 3 as 2 points, and factor 4 as 0, 1, or 2 points for more than 30, 9 to 30, or less than 9 months, respectively. We categorized patients into three risk subgroups based on their total points (0, 1‐3, and 4‐5 points), indicating the usefulness of this scoring system for prognosis prediction and treatment selection. Subgroup comparison revealed OS after ReASCT to be higher than that after allo‐SCT in the intermediate‐risk subgroup comprising the largest population (28.2% vs 21.5%, P < .004). We observed no significant advantages of allo‐SCT over ReASCT in the low‐ and high‐risk subgroups. These findings suggest that ReASCT is more advantageous than allo‐SCT in many patients with MM relapsing/progressing after the prior ASCT. However, long‐term survival patients were noted only in the allo‐SCT group, and allo‐SCT could exhibit clinical efficacy, particularly in the low‐risk group. While further examination is warranted, allo‐SCT could be a potential tool for a specific population with MM relapsing/progressing after the prior ASCT.     

Rituximab purging and maintenance therapy combined with autologous stem cell transplantation in patients with diffuse large B-cell lymphoma

The aim of this prospective, single-arm study was to test the efficacy and tolerability of autologous stem cell transplantation (auto-SCT) combined with in vivo rituximab purging and post-transplant rituximab maintenance therapy in patients with diffuse large B-cell lymphoma (DLBCL). This study included 12 DLBCL patients aged 18-65 years with an International Prognostic Index ≥2. The patients received 4-6 cycles of induction therapy consisting of rituximab plus cyclophosphamide, adriamycin, vincristine and prednisone followed by salvage therapy prior to stem cell mobilization. This regimen was followed by rituximab maintenance therapy (375 mg/m(2) every three months for two years). Prior to auto-SCT, six patients (50%) achieved complete remission (CR) and six (50%) achieved unconfirmed complete remission (CRu). Three months after transplantation, 11 patients (91.7%) achieved CR and one achieved CRu. After two cycles of rituximab maintenance therapy, all 12 patients achieved CR. Long-term CR was achieved by 10 patients, while two experienced relapse at 14 and 20 months after the end of rituximab maintenance therapy. The median follow-up period was 44 months (range 35-61). Disease-free survival was noted in 10 patients, while two experienced relapse. The three-year overall survival (OS) and progression-free survival (PFS) were 100 and 83%, respectively. Prolonged hypogammaglobulinemia occurred in two patients, although no increase in major infections was observed. Hepatitis B surface antigen was continuously negative in all 12 patients. Our results demonstrated that auto-SCT combined with in vivo rituximab purging and post-transplant rituximab maintenance is safe and effective, and may extend OS and PFS in younger high-risk DLBCL patients.     

Maintenance rituximab after autologous stem cell transplantation in patients with mantle cell lymphoma

BackgroundHigh-dose therapy and autologous stem cell transplantation (ASCT) improves outcomes for patients with mantle cell lymphoma (MCL), but relapse ultimately occurs in most patients. Recently presented interim results from a phase III prospective trial suggest maintenance rituximab (MR) after ASCT for MCL improves progression-free survival (PFS). The maturation of these data and any benefit of MR on overall survival (OS) remain to be defined.Patients and methodsIn this retrospective study, we examined a cohort of consecutive patients with MCL that underwent ASCT for MCL at our center and evaluated their outcomes according to whether they received MR after ASCT (n = 50) or did not (n = 107). MR was treated as a time-dependent covariate to account for variation in timing of its initiation.ResultsMR was associated with an improved PFS [hazard ratio (HR) 0.44; confidence interval (CI) (0.24–0.80), P = 0.007] and overall survival (OS; HR 0.46; CI 0.23–0.93, P = 0.03) following a multivariate adjustment for confounding factors with a median follow-up of ∼5 years. Grade 4 neutropenia was increased (34% versus 18%, P = 0.04) in the MR group, but no effect on the rate of mortality unrelated to relapse was observed.ConclusionsThese data support that MR after ASCT for MCL confers a benefit in PFS and additionally suggest it may improve OS. General application of this strategy will require confirmation of benefit in prospective randomized trials.