Postremission therapy for acute myeloid leukemia in the first remission

The medical records of 99 patients with acute myeloid leukemia (AML; except AML, M3) in the first remission from 1995 to 2004 were retrospectively reviewed. When they achieved complete remission, at first complete remission (CR1), patients received allogeneic (n = 23), autologous hematopoietic stem cell transplantation (HSCT) (n = 35), or intensive chemotherapy (n = 41) according to prognostic factors and donor availability. There was an advantage in terms of event-free survival (EFS, p = 0.0001) and overall survival (OS, p = 0.0002) with HSCT as compared to those of intensive chemotherapy. However, the EFS and OS were not different between allogeneic HSCT and autologous HSCT. In high-risk patients, the EFS and OS of allogenic or autologous HSCT group were higher compared with those in the intensive chemotherapy group (p < 0.01). However, there was no difference between allogeneic HSCT and autologous HSCT in terms of EFS and OS. In the intermediate- or low-risk group, there was no significant difference in the outcome according to the postremission modalities.     

Importance of combined-modality therapy for primary bone lymphoma

Primary bone lymphoma (PBL) is a rare entity and comprises about 5% of all extranodal non-Hodgkin's lymphomas (NHL) and 7% of all primary bone tumors. To date there is no consensus about the optimal treatment for PBL. We retrospectively reviewed all cases of PBL treated at Hospital S?o Paulo, Brazil, over a 10-year-period (January 1992-January 2002). Medical records of 7 patients with PBL were reviewed and information on age at diagnosis, sex, NHL clinical staging (CS), treatment and response to treatment were retrieved. Five patients (72%) received combined-modality therapy (CMT) and all of them are in complete remission (CR) with a median follow up of 19 months (ranging from 12 to 144 months). We conclude that PBL is a potentially curable malignancy and treatment should be undertaken in a multiprofessional approach, in order to provide the best support which probably has to include chemotherapy, radiotherapy and, for patients with IPI higher than 2, consolidation with stem-cell transplantation.     

Autologous hematopoietic stem cell transplantation in chemotherapy-sensitive lymphoblastic lymphoma: treatment outcome and prognostic factor analysis

Objective: The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation(AHSCT) in the treatment of lymphoblastic lymphoma(LL).Methods: We retrospectively analyzed the data from 41 patients with chemotherapy-sensitive LL who underwent hematopoietic stem cell transplantation(HSCT) from December 1989 to December 2009 in a single institution.Results: HSCT was conducted as first-line consolidation therapy and salvage therapy in 36 and 5 patients, respectively. The median follow-up was 97.1 months(range, 24.6-173.1 months). The 5-year overall survival(OS) and event-free survival(EFS) rate were 64% and 47% for the initially treated patients, respectively, and were both 20% for the relapsed ones. Bone marrow(BM) involvement and chemotherapy cycles prior to transplantation were identified as significant prognostic factors for EFS in multivariate analysis.Conclusions: These results confirm that AHSCT is a reasonable option for chemotherapy-sensitive LL patients in first complete remission(CR1).     

A prospective study of autologous bone marrow or peripheral blood stem cell transplantation after intensive chemotherapy in myelodysplastic syndromes. Groupe Fran?ais des Myélodysplasies. Group Ouest-Est d'étude des Leucémies aigu?s myélo?des.

We prospectively assessed autologous stem cell transplantation for consolidation treatment in a trial of intensive chemotherapy in high risk myelodysplastic syndromes (MDS). In this trial, patients aged 55 years or less with no HLA-identical sibling and achieving CR were scheduled to receive unmanipulated autologous bone marrow transplantation (ABMT) preceded by a consolidation chemotherapy course. Forty-two of the 83 patients aged 55 years or less included in the trial (51%) achieved CR. Three were allografted in CR. Twenty-four of the remaining 39 patients who achieved CR (62%) received ABMT (16 patients) or autologous peripheral blood stem cell transplantation (APSCT) (eight patients). Indeed, as bone marrow harvest was often insufficient, APSCT was subsequently proposed after mobilization by consolidation chemotherapy followed by G-CSF. The conditioning regimen combined cyclophosphamide and busulfan. ABMT and APSCT were performed 1-7 months (median 3) after CR achievement. Hematological reconstitution occurred in all patients and tended to be faster after APSCT than ABMT although not significantly. Three patients died from the procedure, nine relapsed after 2-26 months and 12 (50%) were still in CR after 8-55 months. In autografted patients, median Kaplan-Meier disease-free survival and survival were 29 and 33 months from the autograft, respectively. Thus, ABMT or APSCT can be performed in almost two-thirds of MDS patients who achieve CR with intensive chemotherapy. PBSC collection may yield higher numbers of stem cells than marrow collection in some cases, and could improve the percentage of MDS patients autografted in CR. Longer follow-up is required to determine if autograft will prolong CR duration in at least some patients.     

Role of hematopoietic stem cell transplantation for relapsed acute promyelocytic leukemia: A retrospective analysis of JALSG‐APL97

For patients with relapsed acute promyelocytic leukemia (APL), all‐trans retinoic acid‐based salvage regimens can achieve second complete remission (CR2), but the optimal post‐remission strategy for APL patients after CR2 remains unclear. Hematopoietic stem cell transplantation (HSCT) during CR2 might be effective, but data on the role of HSCT for APL patients after CR2 are limited in Japan. We retrospectively analyzed outcomes for 57 relapsed APL patients who achieved CR2 in the JALSG APL97 study. Of those, six received autologous (auto)‐HSCT, 21 received allogeneic (allo)‐HSCT, and 30 received various regimens other than HSCT. The 5‐year event‐free survival (EFS) rate, overall survival (OS) rate and cumulative incidence of relapse (CIR) were 50.7%, 77.4% and 51.0% in the non‐HSCT group, 41.7%, 83.3% and 58.3% in the auto‐HSCT group and 71.1%, 76.2% and 9.8% in the allo‐HSCT group, respectively. Both the EFS rate and CIR were significantly better in the allo‐HSCT group than in other groups. Allo‐HSCT appears effective in APL patients in CR2, with a low relapse rate beyond a relatively early transplantation‐related mortality (19%). Among older patients (age ≥40 years), the 5‐year OS was significantly better in the non‐HSCT group than in the HSCT group (78.0% vs 40.5%; P = 0.04). Further prospective studies with larger patient numbers are required to confirm the impact of HSCT alone and in combination with arsenic trioxide on outcomes for patients with APL in CR2.     

Syngeneic hematopoietic stem cell transplantation for acute myeloid leukemia: a propensity score-matched analysis

The present study evaluated outcomes and prognostic factors in adult patients with acute myeloid leukemia (AML) after syngeneic hematopoietic stem cell transplantation (HSCT). Among patients in first complete remission (CR1), outcomes of syngeneic HSCT (Syn) were compared with those of autologous HSCT (Auto), allogeneic HSCT from human leukocyte antigen (HLA)-matched sibling donor (MSD), or allogeneic HSCT from HLA-matched unrelated donor (MUD). Among 11,866 patients receiving first HSCT, 26 in the Syn group were analyzed. The 5-year overall survival (OS) rate, the cumulative incidence of relapse, and the cumulative incidence of non-relapse mortality (NRM) were 47.8%, 59.6%, and 4.6%, respectively. The OS was significantly better in patients in CR1 (n = 13) than in patients in non-CR1 (P = 0.012). Furthermore, 39 patients in CR1 each were assigned to the Auto, MSD, and MUD groups using propensity score matching. The 5-year OS in the Syn (68.4%) was not significantly different from those in the Auto (55.9%, P = 0.265), MSD (62.4%, P = 0.419), or MUD (63.7%, P = 0.409) groups. A higher relapse in the Syn than in the MSD and MUD groups was offset by lower NRM. In summary, syngeneic HSCT might be an alternative option for AML patients in CR1.Subject terms: Acute myeloid leukaemia, Cancer immunotherapy     

Autologous hematopoietic stem-cell transplantation for children with acute myeloid leukemia in first or second complete remission: a prognostic factor analysis.

PURPOSE: To determine prognostic factors correlated with outcomes after autologous hematopoietic stem-cell transplantation (HSCT) in children with acute myeloid leukemia (AML). PATIENTS AND METHODS: We studied 219 children who received autologous HSCT for AML in first complete remission (CR) and 73 children in second CR and who were reported to the Autologous Blood and Marrow Transplant Registry. Among 29 of 73 patients who underwent transplantation in second CR, duration of first CR was > or = 12 months. RESULTS: Three-year cumulative incidences of relapse were 37% (95% CI, 31% to 44%), 60% (95% CI, 41% to 74%), and 36% (95% CI, 20% to 53%) for children in first CR, second CR after a short (< 12 months) first CR, and second CR after a long (> or = 12 months) first CR, respectively. Corresponding 3-year probabilities of leukemia-free survival were 54% (95% CI, 47% to 60%), 23% (95% CI, 10% to 39%), and 60% (95% CI, 42% to 75%). In multivariate analyses, risks of relapse, mortality, and treatment failure (relapse or death, inverse of leukemia-free survival) were higher for patients in second CR after a short first CR than for the other two groups. Transplant-related mortality, treatment failure, and overall mortality rates were higher in older (> 10 years) children. CONCLUSION: Duration of first CR seems to be the most important determinant of outcome. Results in children who experience treatment failure with conventional chemotherapy support the use of autologous transplantation as salvage therapy if such patients achieve a subsequent CR.     

Aggressive natural killer cell leukemia: therapeutic potential of L-asparaginase and allogeneic hematopoietic stem cell transplantation

We conducted a retrospective Japan-Korea multicenter study to better elucidate the clinicopathologic features and therapeutic modalities for aggressive natural killer cell leukemia (ANKL). A total of 34 patients were analyzed. The median age of the patients was 40 years. Among the patients in the study, four had a history of Epstein-Barr virus-related disorders. Three types of ANKL cells were categorized according to their morphological features. Leukemic cells were below 20% in both peripheral blood and bone marrow of 11 patients. The clinical characteristics and prognoses of these 11 patients did not differ significantly from those of the others. As an initial therapy, l-asparaginase chemotherapy resulted in a better response. A total of six patients received allogeneic hematopoietic stem cell transplantation (HSCT) and two received autologous HSCT, with all in non-complete remission (CR). After HSCT, four with allogeneic and one with autologous HSCT reached CR. Median survival of all patients was 51 days. Median survival for the patients with and without HSCT were 266 and 36 days, respectively. A total of two patients with allogeneic HSCT were alive and in CR. All patients without HSCT died of ANKL. The use of L-asparaginase was indicated as a factor for longer survival (HR 0.33, 95% confidence interval; 0.13-0.83, P = 0.02). Early diagnosis of ANKL, l-asparaginase-based chemotherapy and allogeneic HSCT might lead to improved patient outcomes.     

Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic acid therapy followed by timed sequential chemotherapy and stem cell transplantation. APL Study Group. Acute promyelocytic leukemia.

The purpose of this study was to assess the safety and efficacy of stem cell transplantation (SCT) mainly autologous SCT as consolidation therapy in APL patients who relapsed and achieved a second complete remission (CR2). Fifty adult patients with a first relapsed APL, of whom 39 had been previously treated with ATRA, entered a multicenter trial of oral ATRA until complete remission (CR) achievement followed by timed sequential chemotherapy (EMA combining etoposide 200 mg/m2/day for 3 days, mitoxantrone 12 mg/m2/day for 3 days, and cytarabine 500 mg/m2/day for two sequences of 3 days). EMA was started either after CR achievement, or on day 1 of ATRA because of initial white blood cell (WBC) counts >5 x 10(9)/l, or rapidly added to ATRA in order to prevent ATRA syndrome because WBC count increased under ATRA. Forty-five patients (90%, 95% CI 78%-97%) were in CR after induction therapy. Five patients died from infection during aplasia following EMA chemotherapy. Eleven patients who achieved CR had a familial HLA-identical donor and were allografted. The median disease-free survival (DFS) of allografted patients was 8.2 months. The 34 other CR patients were scheduled for autologous peripheral blood (PB) SCT (intent-to-treat group). Actually, autologous transplantation was only carried out in 22 patients (65%) (17 PBSCT and five autologous bone marrow transplantation (BMT)). Reasons for not autografting were early relapse (three patients), severe toxicity of EMA chemotherapy (six patients), and refusal or failure of stem cell harvest (three patients). The 3-year DFS rate of patients actually autografted was 77%. Among the 17 autografted patients still in CR2, nine patients have already reached a longer CR2 than first CR (CR1). Results of detection of PML/RARalpha by RT-PCR after autologous transplantation show negative findings in eight of the nine patients tested. We conclude that (1) ATRA combined to EMA chemotherapy is effective in the treatment of relapsed APL; (2) allogeneic BMT may be too toxic after salvage treatment including EMA intensive chemotherapy; (3) clinical outcome of autografted patients and preliminary molecular results regarding detection of PML/RARalpha after autologous PBSCT are encouraging.     

Transplant-finalized salvage of adult acute lymphoblastic leukemia: results of a mitoxantrone- and methotrexate-based regimen in 36 patients

Idarubicin-based induction programs in acute lymphoblastic leukemia (ALL) account for 75 - 85% of complete remission rate. A small amount of patients exhibit primary refractoriness, and approximately 60% of those achieving a remission eventually relapse. The present study aimed to review the outcome of patients relapsing after or resistant to an idarubicin-based, induction-consolidation regimen (with/without additional high dose cytarabine). The 'ABC' phase II trial consisted of mitoxantrone (50 mg/m² over 5 days) associated with high-dose methotrexate (1.5 g/m² over 24 h, followed by folinic acid rescue), high-dose methyl-prednisolone (125 mg b.i.d.) and vincristine, plus granulocyte colony-stimulating factor. Eligible patients were treated with two courses ('A' and 'B', the latter with reduced drug dosages), followed by allogeneic or autologous haematopoietic stem cell transplantation (HSCT, 'C'). Thirty-six patients (3 primary resistant, 33 at first marrow relapse) were evaluated. With 'A', 21 achieved a complete remission (CR), 10 were refractory and 5 died early. Eighteen patients received 'B' (with one more CR, for an overall CR rate of 61%) and, eventually, 12 patients had 'C' procedures (7 autologous, 5 allogeneic HSCT). WHO grade ≥ 3 treatment-related toxicity developed in 50% and 34% of 'A' and 'B' courses, respectively. The median duration of CR was 5.2 (range 0.5 - 19.7) months and median overall survival was 7.6 (range 0.5 - 20) months. In spite of 12 HSCTs, there was no long-term survivor. 'ABC' salvage proved feasible and comparable to reported rescue chemotherapic regimens, but the achievement of cure in refractory/relapsing ALL remains an outstanding clinical task.     

造血干细胞移植治疗慢性髓系白血病的疗效分析

背景与目的：慢性髓系白血病(chronic myelogenous leukemia,CML)是一种常见的恶性血液疾病,造血干细胞移植(hematopoietic stem cells transplantation,HSCT)是治疗CML最主要的手段。本研究评价自体(auto-)或异体(allo-)HSCT治疗CML的临床疗效。方法：44例CML息者接受HSCT治疗,其中8例采用净化auto-HSCT,30例采用相关allo—HSCT,6例采用无关allo-HSCT;预处理方案：31例接受TBI CY(全身放疗 环磷酰胺)方案,12例采用改良BuCY(羟基脲、马利兰、阿糖胞苷、环磷酰胺)方案,1例采用MACC(马法兰、阿糖胞苷、环磷酰胺、环已亚硝脲)方案;移植物抗宿主病(GVHD)预防：相关移植采用CsA MTX(环孢素A 甲氨蝶呤)方案,无关移植采用CsA MTX MMF(霉酚酸酯) ATG(抗胸腺细胞球蛋白)方案。此外,移植前加速期和急变期患者单用CsA。Kaplan—Meier生存模型评估移植后无病生存。结果：8例接受激活骨髓(ABM)联合反义寡核苷酸或联合STI571体内外净化auto-HSCT后,除1例死于移植中相关并发症外,其余均获得部分或完全细胞或分子遗传学缓解,其中1例急变期患者血液学完全缓解(CR)后移植获分子遗传学CR达81个月。36例allo—HSCT患者除1例死于肝静脉闭塞综合征(hepatic veno-occlusive disease,VOD)和1例移植前急变患者移植后无效以外,其余患者均获CR。移植中感染发生率为38．6％,VOD发生率为9．1％,出血性膀胱炎(hemorrhagic cystitis,HC)发生率为15．9％,巨细胞病毒(CMV)性肺炎为11．4％,VOD、HC和CMV肺炎均发生在allo-HSCT患者。急性GVHD发生率在相关与无关移植中分别为40．0％与33．3％。在相关移植中慢性GVHD发生率为43．4％。移植相关死亡率在自体与异体HSCT中分别为12．5％与16．7％,auto—HSCT复发率为37．5％,相关allo-HSCT复发率为13．3％。移植后5年无病生存率在自体与相关异体移植中分别为18．7％与53．7％。移植前慢性期与加速期和急变期患者相关allo-HSCT后5年无病生存率分别为66．4％与26．7％。结论：allo—HSCT对CML患者,尤其是慢性期患者具有较高的临床治愈率;CsA MTX MMF ATG四联方案在无关allo-HSCT中应用能降低移植后急性GVHD的发生率及程度;采用净化骨髓自体移植能延长CML患者生存期,甚至少部分患者可获得临床治愈。     

Multicenter randomized phase II trial of idarubicin vs mitoxantrone, combined with VP-16 and cytarabine for induction/consolidation therapy, followed by a feasibility study of autologous peripheral blood stem cell transplantation in elderly patients with acute myeloid leukemia.

To compare the antileukemic efficacy of idarubicin and mitoxantrone in elderly patients with acute myeloid leukemia (AML) and to evaluate the feasibility of autologous transplantation using PBSC after consolidation in those with a good performance status, 160 patients (median age 69 years), with AML at diagnosis, 118 of them with de novo AML and 42 with AML secondary to myelodysplastic syndrome or toxic exposure (sAML), received induction treatment with idarubicin, 8 mg/m2/day or mitoxantrone, 7 mg/m2/day, on days 1, 3, and 5, both combined with VP-16, 100 mg/m2/day on days 1 to 3 and cytarabine (araC), 100 mg/m2/day, on days 1 to 7. G-CSF, 5 microg/kg/day, was administered after chemotherapy in patients aged more than 70 years. Patients in complete remission (CR) received one course of consolidation using the same schedule as for induction except the araC administration was shortened to 5 days. Some patients younger than 70 years were then scheduled for autologous stem cell harvest on days 5 to 7 of G-CSF, 5 microg/kg/day, initiated after hematopoietic recovery from consolidation. Autologous transplantation was performed following an additional chemotherapy conditioning. Ninety-five patients (59%) achieved CR, without significant difference between the idarubicin (56% CR) and mitoxantrone (63% CR) group. There was also no significant difference in CR rate between de novo AML (63%) and secondary AML (55%) (P = 0.12). Patients aged < 70 years had 67% CR, while patients aged > or = 70 years had 49% (P = 0.02). There was no significant difference in the duration of aplasia between the two arms. Median time to neutrophil recovery was 22 days in patients who received G-CSF following induction and 27 days in patients who did not (P = 0.006). Severe extrahematologic toxicities of induction did not differ between the two arms and included sepsis (39%), diarrhea (13%), hyperbilirubinemia (8%), hemorrhage (6%) and vomiting (6%). Overall, 14 patients (9%), died from toxicity of induction. First consolidation was administered in 74 patients of whom seven (9%) died from toxicity. Nineteen patients have received transplantation. Median time to recovery of neutrophils > 0.5 x 10(9)/l was 13 days and of platelets > 50 x 10(9)/l 43 days following consolidation. There were two toxic deaths. Median disease-free survival and survival from time of achieving CR of non transplanted patients are 6 and 7 months respectively without difference between the two arms. Fourteen transplanted patients relapsed at a median of 5 months post-transplant. We conclude that this regimen is well tolerated and has a good efficacy to induce CR, without a significant difference in efficacy and toxicity between idarubicin and mitoxantrone. Intensive postinduction, including transplantation, is feasible; however, this procedure did not seem to prevent early relapse in the majority of patients. Neither the high rate of CR nor consolidation nor transplant procedure in a selected group of patients did translate into improved DFS and/or survival.     

Hematopoietic Stem Cell Transplantation for Patients with Chronic Myeloid Leukemia

OBJECTIVE To evaluate the effects of autologous and allogeneic hematopoietic stem cell transplantation (HSCT) for patients with chronic myeloid leukemia(CML).METHODS Fifty-seven patients with CML were treated by HSCT, including 8 cases treated with autologous transplantation purged in vivo and in vitro of minimal residual disease (MRD), 39 cases with related donor allogeneic HSCT (allo-HSCT) and 10 cases with unrelated donor alIo-HSCT. The conditioning regimen was a TBI (total-body irradiation) CY (cyclophosphamide, CTX) protocol in 32 patients, a modified BuCY (hydroxyurea, busulfan, Ara-C, CTX) protocal in 24 patients, and a MACC ( Melphalan, Ara-C, CTX and chlorethyl cyclohexyl nitrosourea ) protocol in one patient. Cyclosporine (CsA) and methotrexate (MTX) were used in patients with related-donor allo-HSCT, and CsA and MTX were added to mycophenolate mofetil (MMF) and antithymocyte globulin (ATG) in unrelated donor allo-HSCT for graft versus host disease (GVHD) prophylaxis. Otherwise, CsA was only used for GVHD prophylaxis in patients with accelerated phase (AP) and blast crisis (BC). The Kaplan-Meier survival analysis model was used to estimate the overall survival (OS) and the disease-free survival (DSF) at 5 years after transplantation.RESULTS Eight patients with autologous transplantation, except for 1 case who died of transplantation-related complications, obtained cytogenetic part or complete remission (CR) within 3 months after transplantation. One patient, who was in BC and obtained CR in hematology before transplantation, had been in molecular CR for 92 months after autologous transplantation. Among the 49 patients treated with alIo-HSCT, all obtained CR, except for one patient who died of hepatic veno-occlusive disease (VOD) and one who had not obtained CR. The incidence of infection and VOD was 33.3% and 7.0%, respectively, during transplantation. After transplantation the incidence of hemorrhagic cystitis (HC) and cytomegalovirus (CMV) interstitial pneumonia (IP) was 22.8% and 8.8%, respectively. VOD, HC and CMV IP did not occur in patients with autologous transplantation. The incidence of acute GVHD and the frequency of chronic GVHD was 41.0% and 48.6%, respectively, in patients with related and unrelated transplantation. The rate of relapse in patients with autologous and allogeneic transplantation was 57.1% and 12.8%, respectively. The DFS at 5 years after transplantation was 25.0% and 61.7%, respectively, in patients with autologous and related donor transplantation. The DFS at 5 years was 70.7% and 34.1%, respectively, in patients with CP (chronic phase) or AP and BC before transplantation.CONCLUSION AIIo-HSCT may have a higher clinical cure rate for CML patients with CP. The CsA MTX MMF ATG protocol is more effective for acute GVHD prophylaxis and can decrease the incidence and degree of GVHD in patients with unrelated donor transplantation, Autologous transplantation with purged bone marrow can prolong the survival time of CML patients and some may be cured with transplants of this type.     

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     

Targeting complete response with upfront bortezomib consolidation versus observation after the achievement of complete response following autologous transplantation for multiple myeloma (TUBA study)

Complete response (CR) after treatment for multiple myeloma is associated with superior progression‐free survival (PFS). Multiple myeloma patients were prospectively recruited for induction treatment with bortezomib and dexamethasone (BD) followed by autologous hematopoietic cell transplantation (auto‐HCT) between 2010 and 2012. If patients did not achieve CR after auto‐HCT, BD consolidation therapy was added to target CR. After the BD induction phase (n = 46), greater than or equal to CR was achieved in 4 patients (8%). After auto‐HCT (n = 34), greater than or equal to CR was achieved in 9 patients (20%) and very good partial response (VGPR) was achieved in 11 (24%). Of the 24 patients who received auto‐HCT and whose response was less than CR, 21 received BD consolidation therapy for a median of 4 courses. Finally, the maximum response with or without BD consolidation was greater than or equal to CR in 19 (41%), VGPR in 7 (15%), and PR in 6 (13%). Through BD consolidation, CR was achieved in 8 of 11 patients with post‐HCT VGPR and in 2 of 12 patients with post‐HCT PR. In total, 4 year PFS and overall survival were 43 and 80%, respectively. After adjusting for clinical factors, there was no difference in PFS between CR patients after auto‐HCT and BD consolidation, while patients with less than or equal to VGPR after consolidation had a significantly lower PFS. Patients with post‐HCT CR showed good PFS, and targeting CR through BD consolidation could improve the CR rate. It would be worthwhile to prospectively compare the efficacy of consolidation only for patients who failed to achieve CR to a universal consolidation strategy.     

Haploidentical hematopoietic stem cell transplantation in adults with Philadelphia‐negative acute lymphoblastic leukemia: No difference in the high‐ and low‐risk groups

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective post‐consolidation therapy and curative option for adult patients with Philadelphia chromosome‐negative (Ph‐negative) acute lymphoblastic leukemia (ALL) in first complete remission (CR1). A human leukocyte antigen (HLA)‐haploidentical related donor (haplo‐RD) is one of the most important alternative sources for those without HLA‐identical sibling donor (ISD). The present study aimed to evaluate the outcomes of haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) in adult Ph‐negative ALL CR1 patients (n = 183). We produced an unmanipulated haplo‐HSCT protocol including granulocyte colony stimulating factor (G‐CSF) for all donors, intensive immune suppression, anti‐thymocyte globulin, and combination of G‐CSF‐primed bone marrow harvest and G‐CSF‐mobilized peripheral blood stem cells harvest as the source of stem cell grafts. The median age for high‐risk versus low‐risk groups were 29 versus 23 years. Three‐year incidences of relapse mortality and nonrelapse mortality for high‐risk versus low‐risk groups were 7.1% versus 11.1% (p = 0.498) and 18.0% versus 16.2% (p = 0.717), respectively. Three‐year probabilities of disease‐free survival and overall survival for high‐risk versus low‐risk groups were 67.6% versus 68.2% (p = 0.896) and 74.9% versus 72.7% (p = 0.981), respectively. Multivariate analysis showed that limited cGVHD and a lower pre‐HSCT comorbidity burden were associated with better outcomes. In summary, comparable outcomes were observed among high‐ and low‐risk Ph‐negative ALL CR1 patients after haplo‐HSCT. Haplo‐RD could be considered for adults with Ph‐negative ALL in CR1 as an important alternative source of donors in cases when no ISD is available.     

Treatment of advanced neuroblastoma with high-dose melphalan and autologous bone marrow transplantation

Summary Fifteen children with advanced neuroblastoma according to Evans' classification (1 with stage III and 14 with stage IV) were treated with high-dose melphalan (HDM) followed by autologous bone marrow transplantation. Before HDM, all patients had been extensively treated with multimodality therapy for a median duration of 9 months. At the time of HDM, seven children were in partial remission (PR) with measurable residual tumor and 8 were in complete remission (CR) or good partial remission (GPR). No reduction in measurable tumor size was observed in any of the PR patients. However, when HDM was used as consolidation therapy (CR and GPR patients) survival appeared encouraging, since five of eight patients are alive with no evidence of disease at (NED) 29⁺ to 54⁺ mouths after HDM. Tolerance of this high-dose chemotherapy was satisfactory; gastrointestinal toxicity appeared to be the most important limiting factor. These results suggest that chemotherapy including high-dose melphalan is promising when used as consolidation therapy in patients who have already attained CR with conventional therapies.This study was presented in part at the workshop on high-dose chemotherapy with autologous bone marrow transplant. (Cancer Therapy evaluation program, NCI, Bethesda, March 1984)     

Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study.

Mantle cell lymphoma (MCL) is a distinct clinico-pathological entity with a poor prognosis. We have conducted a prospective study in patients with MCL to evaluate a therapeutic strategy in which CHOP polychemotherapy was followed by DHAP if CHOP failed to induce complete remission. Responding patients then proceeded to an intensification therapy with autologous peripheral blood stem cell transplantation (APBSCT). Twenty-eight consecutive patients with newly diagnosed aggressive MCL were included. After four cycles of CHOP regimen, two complete responses (CR) were obtained (7%) and 14 (50%), five (18%) and seven (25%) patients achieved partial (PR), minor (MR) and no response, respectively (one patient died from septic complications during CHOP induction). The two patients in CR after CHOP underwent intensification with TBI, high-dose cyclophosphamide-etoposide and APBSCT. The other twenty-five patients received DHAP and in this group a response rate of 92% (21 CR (84%), two PR (8%)) was observed. Two patients had progressive disease. The twenty-three responding patients received high-dose therapy (TAM8 regimen: TBI-cytarabine-melphalan) followed by APBSCT. One of the two partial responding patients achieved CR after TAM8. After a median follow-up of 47.6 months (range, 14-70), seven patients have relapsed. Our data confirm that: (1) CHOP regimen induces a low CR rate in MCL; (2) CHOP plus DHAP appears to be much more efficient and allows a large proportion of patients to proceed to high-dose therapy in CR; (3) consolidation therapy including TBI and high-dose Arac-C followed by APBSCT may improve event-free survival.     

Autologous stem cell transplantation for nasal NK/T-cell lymphoma: a progress report on its value.

Nasal NK/T-cell lymphoma is an Epstein-Barr virus-related, highly aggressive but localized disease in Orientals. The median survival is <1 year. Here, we update our experience on 18 patients treated with autologous stem cell transplantation (ASCT). Two patients died of mucositis and septicemia during ASCT. Relapse occurred in nine cases, including six local relapses. Compared with patients treated in remission, all patients treated in active or disseminated disease died of early relapse. Within this cohort, there was no significant survival difference between patients treated in first (CR1, n = 7) or second (CR2, n = 5) complete remissions. However, among consecutive cases analyzed, the patients receiving ASCT at CR1 showed a trend towards better overall survival compared with historical matched controls (P = 0.064). Disease relapse beyond 6 months was not seen after ASCT. Our retrospective data suggest that ASCT in CR1 is a viable consolidation therapy for local-stage NK/T lymphoma, but a randomized trial is needed to prove any definite survival benefit. For patients with relapsed, refractory or extranasal disease, early consideration for allogeneic transplantation and alternative therapy may be warranted.     

Combination therapy with arsenic trioxide, all-trans retinoic acid, and gemtuzumab ozogamicin in recurrent acute promyelocytic leukemia

BACKGROUND: From 20% to 30% of patients with acute promyelocytic leukemia (APL) who are treated with all-trans retinoic acid (ATRA) develop recurrent disease. Arsenic trioxide (ATO) is an effective agent for the salvage of patients with recurrent APL, and gemtuzumab ozogamicin (GO) has shown activity in patients with APL. METHODS: The authors investigated the efficacy of a combination of ATO, ATRA, and GO in 8 patients with APL in first recurrence (7 patients with hematologic recurrences and 1 patient with a molecular recurrence). All patients had received previous treatment with ATRA either alone or in combination with other agents. Patients received ATO 0.15 mg/kg intravenously until they achieved a bone marrow complete remission (CR). Once in CR, patients received consolidation with ATO, ATRA, and GO for 10 months. Patients then received maintenance with idarubicin, ATRA, 6-marcaptopurine, and oral methotrexate for 11 months. RESULTS: All 7 patients who had hematologic recurrences achieved CR after a median of 39 days (range, 21-56 days). After a median follow-up of >/=36 months (range, 4-55 months), 6 patients remained alive in CR, and 2 patients died in CR. Six of 8 patients remained in second CR that was longer than their first CR. All 7 evaluable patients achieved molecular remission. There were no grade 3 or 4 extramedullary toxicities. Two patients died, 1 secondary to a complication of metastatic lung adenocarcinoma, and the other of sepsis. CONCLUSIONS: The combination of ATO, ATRA, and GO was effective and may achieve durable remissions in patients with APL in first recurrence. It should be considered as an effective alternative to allogeneic or autologous transplantation.