Mild chronic graft‐versus‐host disease may alleviate poor prognosis associated with FLT3 internal tandem duplication for adult acute myeloid leukemia following allogeneic stem cell transplantation with myeloablative conditioning in first complete remission: a retrospective study

Internal tandem duplication (ITD) of the FLT3 gene (Fms‐like tyrosine kinase 3) is the most commonly found mutation in acute myeloid leukemia (AML). The significance of FLT3‐ITD at diagnosis was retrospectively estimated for allo‐HSCT (allogeneic hematopoietic stem cell transplantation) outcomes in 140 patients, median age of 38, undergoing allo‐HSCT after myeloablative conditioning in first complete remission of AML. FLT3‐ITD was detected at AML diagnosis in 42/140 (30%) of included into this study patients. At 3 years, relapse incidence (RI) following allo‐HSCT in AML patients with intermediate or normal karyotype was significantly higher in those FLT3‐ITD positive than FLT3‐ITD negative [52.9 vs. 20.4%, P = 0.002]. Additionally, patients with mild chronic graft‐versus‐host disease (cGvHD) had significantly lower RI compared to patients with moderate or severe grade cGvHD or those not experiencing cGvHD, respectively, 4.8 vs. 36.0 vs. 27.8%, P = 0.032. FLT3‐ITD was harboring a poor prognosis in AML with intermediate or normal karyotype and significantly increased risk of relapse following allo‐HSCT. It appears that allo‐HSCT does not cure patients with FLT3‐ITD, unless they develop symptoms of mild cGvHD and graft versus leukemia, which may decrease RI.     

Role of autologous hematopoietic stem cell transplantation according to the NPM1/FLT3‐ITD molecular status for cytogenetically normal AML patients: A GOELAMS study

The choice of postremission therapy for acute myeloid leukemia (AML) patients is now based on the blasts' cytogenetic and molecular profile. However, the potential benefit of autologous hematopoietic stem cell transplantation (auto‐HSCT) according to the NPM1/FLT3‐ITD status has been poorly studied in AML patients with a normal karyotype (NK). Therefore, we evaluated the NPM1/FLT3‐ITD molecular status in 135 NK‐AML patients treated by allogeneic HSCT (allo‐HSCT), auto‐HSCT, or chemotherapy as consolidation therapy within the GOELAMS LAM‐2001 trial. In univariate analyzes, 4‐year leukemia‐free survival (LFS) and overall survival (OS) were significantly higher for NPM1+/FLT3‐ITD? patients compared with patients presenting another molecular profile (61 vs. 43% and 72 vs. 48%, P = 0.02 and P = 0.01, respectively). In the NPM1+/FLT3‐ITD? subgroup, there was no benefit for allo‐HSCT or auto‐HSCT vs. chemotherapy (4‐year LFS: 71, 56, and 60%; 4‐year OS: 73, 71, and 60%, respectively; P = NS). For patients with other NPM1/FLT3‐ITD molecular profiles, allo‐HSCT was found to be the best consolidation therapy, whereas auto‐HSCT was associated with a better outcome when compared with chemotherapy (allo‐HSCT‐, auto‐HSCT‐, and chemotherapy‐related 4‐year LFS: 68, 44, and 36%, P = 0.004; 4‐year OS: 68, 52, and 29%, respectively, P = 0.02). Our study indicates that allo‐HSCT and auto‐HSCT provide similar outcomes compared with chemotherapy as consolidation for NPM1+/FLT3‐ITD? NK‐AML patients. For NK‐AML patients with an adverse molecular profile, auto‐HSCT could represent an alternative therapeutic approach when no human leukocyte antigen–matched allogeneic donor is available. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.     

Maintenance therapy for FLT3-ITD-mutated acute myeloid leukemia

FLT3-ITD is a constitutively activated variant of the FLT3 tyrosine kinase receptor. Its expression in acute myeloid leukemia (AML) is associated with a poor prognosis. Due to this, the development of tyrosine kinase inhibitors (TKI) blocking FLT3-ITD became a rational therapeutic concept. This review describes key milestones in the clinical development of different FLT3-specific TKI with a particular focus on FLT3-TKI maintenance therapy in remission after allogeneic hematopoietic stem cell transplantation (HCT). Recent evidence from randomized trials using sorafenib in FLT3-ITD mutated AML provided a proof of concept that targeted post-HCT maintenance therapy could become a new treatment paradigm in AML.     

异基因造血干细胞移植治疗Fms样酪氨酸激酶3基因内部串联重复(FLT3-ITD)阳性的急性髓性白血病的疗效分析

 目的 分析异基因造血干细胞移植(allo-HSCT)治疗伴有Fms样酪氨酸激酶3基因内部串联重复(FLT3-ITD)阳性的急性髓性白血病(AML)的疗效,探讨不同移植方式及疾病状态对该类患者预后的影响。方法 2006年10月至2012年10月在苏州大学附属第一医院行allo-HSCT的AML患者共314例,其中FLT3-ITD阳性54例,回顾性分析allo-HSCT对FLT3-ITD阳性AML患者的临床疗效。结果 54例FLT3-ITD阳性患者3年总生存(OS)率为56%, 3年无白血病生存(LFS)率为47%。其中同胞人类白细胞抗原(HLA)全相合及亲缘HLA单倍型相合造血干细胞移植的患者3年OS率分别为56%和60%,3年LFS率为45%和54%。两组在OS时间及LFS时间方面的差异均无统计学意义(χ²=0.074,P=0.786; χ²=0.006,P=0.941)。47例(87.0%)患者移植前本病处于首次完全缓解(CR1),7例(13.0%)患者移植前本病处于非CR1期。处于CR1期的患者的生存显著优于非CR1期患者。结论 allo-HSCT是FLT3-ITD阳性AML患者的有效治疗方法,亲缘HLA单倍型相合造血干细胞移植与同胞HLA全相合移植疗效相似。疾病复发是影响其疗效的主要因素。
        

Is FLT3 internal tandem duplication significant indicator for allogeneic transplantation in acute myeloid leukemia? An analysis of patients from the Czech Acute Leukemia Clinical Register (ALERT)

To assess the prognostic relevance of activating mutations of FLT3 gene on outcome of allogeneic transplantations in AML patients, we performed an analysis of all patients with FLT3 mutations registered in the Czech Acute Leukemia Clinical Register (ALERT) from 2003 till the end of 2005. Within the mentioned period 170 patients with AML of median age 56 years (23-77) were investigated for FLT3 mutation, within them 36 cases (21%) with FLT3 mutations (32 FLT3 ITD and 4 FLT3 D835) were found.Out of FLT3 ITD positive patients 13 had allogeneic transplantation, 20 patients with mutations of FLT3 were treated with chemotherapy without transplantation. Results of the treatment of these patients were compared with the results of the group of patients without FLT3 mutation, which was according to other characteristics identical with the group of patients with FLT3 mutations (n=134). Median overall survival (OS) was significantly shorter for patients with FLT3 ITD (34.8 weeks) than for those without FLT3 mutations (67.7 weeks; P=0.028). Median OS of patients with FLT3 ITD who had allogeneic transplantation was 42.5 weeks; median OS of patients with FLT3 ITD treated only with chemotherapy was 29.6 weeks (P=0.362). After allogeneic transplantation, median OS of FLT3 mutations negative patients was similar to FLT3 ITD positive patients (46.7 versus 42.5 weeks; P=0.443). Our results suggest that at present there is no strong evidence that FLT3 status alone should influence the decision to proceed to allogeneic transplantation in AML patients. Decision to proceed to alogeneic transplantation should not be based on the FLT3 status only, but it should also consider other prognostic factors.     

Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3‐ITD acute myeloid leukaemia in first complete remission

We performed a retrospective study analysing the effect of sorafenib, an oral fms‐Like Tyrosine Kinase 3 (FLT3)/multikinase inhibitor, as post‐transplant maintenance in adult patients with FLT3‐internal tandem duplication (ITD) acute myeloid leukaemia (AML). We identified consecutive patients with FLT3‐ITD AML diagnosed between 2008 and 2014 who received haematopoietic cell transplantation (HCT) in first complete remission (CR1). Post‐HCT initiation of sorafenib (yes/no) was evaluated as a time‐varying covariate in the overall survival/progression‐free survival (OS/PFS) analysis and we performed a landmark analysis of controls alive without relapse at the median date of sorafenib initiation. We identified 26 sorafenib patients and 55 controls. Median follow‐up was 27·2 months post‐HCT for sorafenib survivors, and 38·4 months for controls (P = 0·021). The median time to initiating sorafenib was 68 days post‐HCT; 43 controls were alive without relapse at this cut‐off. Sorafenib patients had improved 2‐year OS in the d+68 landmark analysis (81% vs. 62%, P = 0·029). Sorafenib was associated with improved 2‐year PFS (82% vs. 53%, P = 0·0081) and lower 2‐year cumulative incidence of relapse (8·2% vs. 37·7%, P = 0·0077). In multivariate analysis, sorafenib significantly improved OS [Hazard ratio (HR) 0·26, P = 0·021] and PFS (HR 0·25, P = 0·016). There was no difference in 2‐year non‐relapse mortality (9·8% vs. 9·3%, P = 0·82) or 1‐year chronic graft‐versus‐host disease (55·5% vs. 37·2%, P = 0·28). These findings suggest potential benefit of post‐HCT sorafenib in FLT3‐ITD AML, and support further evaluation of post‐HCT FLT3 inhibition.     

The Successful Complete Remission Induction by Sorafenib Monotherapy in a FLT3-D835Y-Positive Patient with Refractory Acute Monocytic Leukemia

Sorafenib has been shown to be active in AML patients with FLT3-ITD. However, the effect of sorafenib in AML patients with FLT-TKD has never been well determined. Moreover, acquisition of secondary FLT3 TKD mutations, mainly at D835 (D835F/H/V/Y), are recognized as the major mechanisms of resistance of AML patients with FLT3-ITD to sorafenib. It has been reported that sorafenib induced death of cells that expressed the FLT3-ITD or FLT3-D835G but not cells that expressed the FLT3-D835Y point mutant or wild-type FLT3 in vitro. Here, we report the successful complete remission induction by sorafenib monotherapy in a FLT3-D835Y-positive patient with refractory AML-M5 followed by allogeneic stem cell transplantation.     

A critical review of which children with acute myeloid leukaemia need stem cell procedures

The last decades have seen parallel improvements in chemotherapy‐based and haematopoietic stem cell transplantation (HSCT) regimens for acute myeloid leukaemia (AML) in children. There has been no consensus on indication for HSCT. Reserving HSCT for high‐risk and relapsed patients spare many patients from the long‐term toxicity of this treatment. The results of matched unrelated donor HSCT equal family donor transplantation and the presence of a matched sibling should no longer be a transplant indication. Minimal residual disease measured by flow cytometry may identify poor responders benefitting from HSCT in first complete remission (CR1) and those with a favourable response to induction therapy who do not need HSCT even with adverse cytogenetic aberrations. FLT3‐internal tandem duplication without NPM1 mutation has a very high relapse rate despite favourable response and HSCT is indicated in CR1 in these cases. Finding the optimal indications for HSCT is a delicate balance between risk of relapse and late effects.     

Fludarabine/intermediate-dose cytarabine with or without allogeneic hematopoietic stem cell transplantation in poor-risk leukemia: a single center experience

Disease recurrence has been and remains the leading cause of treatment failure in patients with high-risk leukemia.We retrospectively analyzed outcome in 61 patients with high-risk leukemia receiving a combination of fludarabine and intermediate-dose cytarabine as induction (n = 11) or salvage therapy (n = 35). Thirty-six patients having a suitable stem cell donor proceeded to allogeneic hematopoietic stem cell transplantation (HSCT). Ten patients received fludarabine-based salvage therapy without consecutive allogeneic transplantation and 15 patients received fludarabine/intermediate-dose cytarabine because of disease relapse following allogeneic stem cell transplantation. In patients without prior allogeneic HSCT (n = 46) the complete remission rate (CR) was 41% with a CR rate of 46 and 14% in patients with acute myeloid leukemia (AML) and with acute lymphoblastic leukemia (ALL), respectively. Overall survival for patients achieving a CR was 41 versus 0% for patients not achieving CR (P < 0.0001). The best outcome was observed in patients receiving an allogeneic HSCT in CR following fludarabine/intermediate-dose cytarabine (47 vs. 0% for patients not in CR at the time of allografting, P = 0.01). All 10 patients receiving fludarabine/intermediate-dose cytarabine without subsequent allogeneic HSCT died within 3 years either of disease relapse/progression or infection. Only 1/15 (7%) patients receiving fludarabine/intermediate-dose cytarabine because of relapse following allogeneic HSCT became a long-term survivor. By multivariate analysis achieving CR, receiving an allogeneic HSCT, and being in first relapse or untreated were the only parameters that significantly determine the outcome. Although preliminary only high-risk AML patients having a stem cell donor are candidates for fludarabine/intermediate-dose cytarabine and only those achieving a CR should be referred to subsequent allogeneic HSCT. All other patients with high-risk leukemia are candidates for experimental therapies within controlled trials.     

Donor cell‐derived acute promyelocytic leukemia after allogeneic hematopoietic stem cell transplantation

Donor cell leukemia (DCL) is an infrequent complication after allogeneic hematopoietic stem cell transplantation (HSCT). Its true incidence is difficult to assess, although improvements in chimerism studies contributed to a better diagnosis of DCL. We report two rare cases of donor cell‐derived acute promyelocytic leukemia (APL). To our knowledge, only two cases have been described in the literature. Here, we report one male and one female patients with acute myeloid leukemia (AML), who developed an APL in donor cells after HSCT. The latency between HSCT and DCL was 279 and 43 months, respectively. Fluorescent in situ hybridation and chimerism monitoring analysis proved the donor origin of APL. Surprisingly, donor lymphocyte infusion provided a hematological response during 19 months in the female patient. The mechanisms associated with pathogenesis of DCL are unclear and seem to be multifactorial. Increasing worldwide allogeneic hematopoietic stem cell transplantation activity and potentially the age of donor could explain the increasing incidence of DCL in the future. It is highlighted that long‐term follow up of recipients will allow to report all cases of DCL, to clarify the genetic landscape and factors which contribute to DCL, to understand the response to DLI.     

Vascular endothelial growth factor receptor 3 is a novel marker differing CD138‐positive and CD138‐negative multiple myeloma cells

Considering the unsatisfactory results of salvage therapies for patients with relapsed/refractory acute myeloid leukaemia (R/R‐AML), their value before allogeneic haematopoietic stem cell transplantation (HSCT) remains questionable. However, direct allogeneic HSCT following established conditioning regimens applied in patients with R/R‐AML during active disease has been equally disappointing. In this retrospective observational study, high‐dose melphalan, as part of a sequential preparative regimen, followed by a total body irradiation (4 × 2 Gy)‐based or a treosulfan‐based dose‐adapted conditioning therapy for allogeneic HSCT was administered to 292 adult patients (median age 56 years, range 17–74) with primary refractory (144 patients), secondary refractory (97 patients) or relapsed AML (51 patients). Overall survival rates at 3 years were 34%, 29% and 41%, respectively. Risk factors associated with an inferior survival were higher age, transplantation from a human leucocyte antigen‐mismatched donor and high disease burden. Patients transplanted with blast infiltration <20% showed a notable survival rate of 51% at 3 years. In particular, patients with primary refractory AML showed a more favourable outcome when transplanted early during their disease course. Thus, high‐dose melphalan‐based sequential conditioning chemotherapy followed by an allogeneic HSCT is feasible and enables long‐term remission to be achieved in a substantial proportion of patients with active R/R‐AML.     

Allogeneic stem cell transplantation in second rather than first complete remission in selected patients with good-risk acute myeloid leukemia

Through two consecutive trials, a policy that considered allogeneic stem cell transplantation (SCT) from a sibling donor in second rather than first complete remission (CR) in selected younger patients with acute myeloid leukemia (AML) with t(8;21)/inv(16) (core binding factor (CBF) group) or a normal karyotype (NN group) was followed by Acute Leukemia French Association (ALFA) centers. The outcome of 92 of these patients in first relapse (32 CBF, 60 NN) was reviewed with the aim of validating this strategy. The presence of an FLT3 internal tandem duplication (ITD) was retrospectively assessed in 50 patients. A total of 61 patients (66%) reached a second CR. Donor availability was an independent prognostic factor for survival in the whole patient population as well as in the CBF subset, but not in NN patients, further supporting this strategy for CBF-AMLs. In NN patients, FLT3-ITD was the main bad-prognosis factor for second CR achievement and survival, leading to consider SCT earlier, at least in FLT3-ITD patients with a donor.     

Hepatitis B serological changes following allogeneic bone marrow transplantation

Hepatitis B (HBV) reverse seroconversion (RS) in immunocompromised patients with serological evidence of past HBV infection (hepatitis B surface antigen [sAg] negative, core antibody [cAb] positive) has been reported with increasing frequency following allogeneic hematopoietic stem cell transplant (allo‐HSCT). We performed a retrospective review of serial HBV serological testing in patients who had undergone allo‐HSCT at our center between 2000 and 2006. We identified 12 patients with serological evidence of past HBV, including 1 case of RS. Although 7 of these 12 patients had no changes in serological markers detected after transplantation, 5 of them had declining levels of hepatitis B surface antibodies [sAb], with 2 to < 10 IU/mL. The remaining 4 patients with past HBV had loss of antiHBcAb. An additional 14 patients developed isolated antiHBcAb post allo‐HSCT in the setting of receiving HBV screened (HBsAg, antiHBcAb) negative donor stem cells. Monitoring of HBV serological markers (including antiHBsAb) and HBV DNA levels pre allo‐HSCT in recipients and donors, and post allo‐SCT in recipients, would allow early detection and treatment of RS and identify new acquisition of HBV.     

Allogeneic haematopoietic stem cell transplantation in relapsed or refractory anaplastic large cell lymphoma of children and adolescents--a Berlin-Frankfurt-Münster group report

Patients with refractory or early relapsed anaplastic large cell lymphoma (ALCL) have a poor chance of survival. We report 20 children and adolescents with high-risk relapsed or refractory ALCL who underwent allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively analysed 20 patients who relapsed between December 1991 and April 2003 during (six patients) or soon after first-line Berlin-Frankfurt-Münster-type chemotherapy (14 patients) and underwent allogeneic HSCT. Nine patients received allogeneic HSCT after the first relapse and 11 after multiple relapses. Eight patients received their transplants from matched sibling donors, eight from unrelated donors and four from haploidentical family donors. The conditioning regimen was based on total body irradiation in 15 patients. Two patients relapsed after allogeneic HSCT and died. Three patients died of transplant-related toxicity. Event-free survival at 3 years after allogeneic transplant was 75 +/- 10%. There was no influence of donor type or conditioning regimen on outcome. Two of six patients with progressive disease during frontline therapy survived compared with 13/14 patients with a first relapse after frontline therapy. Two of three patients who were transplanted with active lymphoma and all five patients who received allogeneic HSCT for relapse following autologous HSCT survived disease-free. Allogeneic HSCT is effective and has acceptable toxicity as rescue therapy for high-risk ALCL relapse. It even offers cure for patients refractory to chemotherapy, suggesting a graft-versus-ALCL effect.     

Treatment of lymphoma relapses after allogeneic hematopoietic stem cell transplantation with intensive chemotherapy followed by infusion of hematopoietic stem cell from the original donor

Five lymphoma patients relapsed from allogeneic hematopoietic stem cell transplantation (HSCT). Three patients who received myeloablative conditioning had full donor chimerism at relapse, whereas two who received nonmyeloablative conditioning had partially or completely lost the graft. All received mini-BEAM [carmustine (BCNU), etoposide, cytarabine (AraC), melphalan], followed by infusion of HSC (four peripheral blood, one marrow) from the initial donor. Neutropenia and thrombocytopenia were brief, and full donor chimerism was established in all cases. There were four complete and one partial remissions. Graft-versus-host disease occurred in three cases, all with full donor chimerism at relapse. Two patients died subsequently of disease relapse or progression. Another two patients died from fungal infection, one of whom was still in remission at death. One patient had remained in remission 47 months after treatment. Mini-BEAM/HSC is an effective treatment for lymphoma relapses after allogeneic HSCT, but optimal strategies of remission consolidation and prevention of treatment-related complications are needed to improve outcome.     

Tetramer monitoring to assess risk factors for recurrent cytomegalovirus reactivation and reconstitution of antiviral immunity post allogeneic hematopoietic stem cell transplantation

S. Borchers, S. Luther, U. Lips, N. Hahn, J. Kontsendorn, M. Stadler, S. Buchholz, H. Diedrich, M. Eder, U. Koehl, A. Ganser, E. Mischak‐ Weissinger. Tetramer monitoring to assess risk factors for recurrent cytomegalovirus reactivation and reconstitution of antiviral immunity post allogeneic hematopoietic stem cell transplantation.
Transpl Infect Dis 2011: 13: 222–236. All rights reserved Background. Reactivation of cytomegalovirus (CMV) is a major cause of morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). In healthy individuals, virus‐specific T cells (CMV‐CTL) control the reactivation of latent CMV. The monitoring of virus‐epitope‐binding CD8⁺ T cells using major histocompatibility complex‐I‐peptide complexes (tetramers) has recently been established, allowing assessment of the reconstitution of CMV‐CTL post HSCT. Patients and methods. In order to study immune reconstitution and reactivation control through CMV‐CTL, we regularly monitored all patients undergoing allogeneic HSCT in our department for 2 years, who matched at least 1 of 6 commercially available tetramers for common human leukocyte antigen (HLA) types. To verify risk factors for CMV reactivations in our cohorts, clinical characteristics of all patients transplanted within the last 10 years were included in statistical analyses determining the relative risk for single and recurrent CMV reactivations. Results. As expected, CMV serostatus, HLA match, and donor source significantly influenced the risk of recurrent CMV reactivation. Applying CMV‐CTL tetramer monitoring for 2 years allowed the monitoring of 114 (85%) of 134 patients, by testing a set of tetramers representing 6 epitopes from 3 different CMV proteins. The presence of CMV‐CTL before day +50 and their expansion post reactivation seem to protect against recurrent CMV reactivations. The mean number of CMV‐CTL by day +100 was >5‐fold higher in the recipient CMV‐positive/donor‐positive (R+/D+) group (91/μL) compared with the R+/D? (13/μL) and the R?/D+(2/μL) group. Seventy‐nine percent of patients from the R+/D+ setting recovered >10 CMV‐CTL per μL by day +100, while almost 50% of the other groups failed to mount a CMV‐specific response by that time (R+/D?: 58%; R?/D+: 43%). Conclusion. Tetramer monitoring can help to predict (recurrent) CMV reactivation and is a useful approach to monitor individual patients with increased risk for recurrent reactivation post HSCT; thus, it could help to identify patients in need of adoptive transfer of CMV‐CTL or to optimize the use of antiviral drugs.     

A fast and simple approach for the simultaneous detection of hematopoietic chimerism, NPM1, and FLT3-ITD mutations after allogeneic stem cell transplantation

Hematopoietic chimerism can be used as a tool for patient management after allogeneic hematopoietic stem cell transplantation (HSCT). An increase in the proportion of recipient cells after transplantation is strongly associated with relapse in chronic myeloid leukemia. However, in acute myeloid leukemia (AML) the significance of increasing mixed chimerism (MC) as a predictive marker for relapse is less clear. Several mutations frequently found in AML have been employed for minimal residual disease detection and relapse prediction. Therefore, a combined analysis of hematopoietic chimerism and of the molecular aberrations found in AML could be used to improve MC characterization. We developed a multiplex PCR for use in the simultaneous detection of hematopoietic chimerism and mutations in nucleophosmin (NPM1) and fms-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD). A total of 303 samples from 20 AML patients were analyzed after HSCT. The microsatellite markers used for hematopoietic chimerism detection were D1S80, D7S1517, D4S2366, THO1, and SE33. A total of 149 samples from 18 patients showed MC with a mean detection time of 9.7 months. From the 18 patients with MC, in 6 of the patients, no FLT3-ITD or NPM1 mutation was found at any time point tested, and these patients remained in complete hematological remission. In 12 patients with MC, FLT3-ITD and NPM1 mutations were found, and these patients showed signs of hematological relapse. Our combined analysis of NPM1/FLT3-ITD mutations and hematopoietic chimerism improved the characterization of patients with MC after HSCT. The present approach may be further expanded by combining additional mutations found in AML with hematopoietic chimerism detection.     

Successful cell‐mediated cytokine‐activated immunotherapy for relapsed acute myeloid leukemia after hematopoietic stem cell transplantation

Acute myeloid leukemia (AML) is an extremely aggressive disease with a high relapse rate even after allogeneic hematopoietic stem cell transplantation (HSCT). We report the successful outcome of cell‐mediated cytokine‐activated immunotherapy in a high‐risk pediatric AML patient who relapsed shortly after allogeneic HSCT. Donor lymphocyte infusion along with interferon induced a graft‐versus‐leukemia effect, presenting as a reversible episode of graft‐versus‐host disease, which led to stable complete donor chimerism and total eradication of AML for over 24 months, at the time of this report. The curative potential of immunotherapy in hematological malignancies is discussed. Am. J. Hematol., 2009. © 2008 Wiley‐Liss, Inc.     

异基因造血干细胞移植治疗NK／T细胞淋巴瘤

目的：探讨异基因造血干细胞移植（allo—HSCT）治疗NK／T细胞淋巴瘤的疗效。方法：对1例NK／T细胞淋巴瘤患者进行allo-HSCT,采用改良马利兰（Bu）／环磷酰胺（Bu／Cy）预处理方案进行了亲缘HLA全相合的外周血干细胞移植,移植物抗宿主病（GVHD）的预防采用环孢素A联合短疗程甲氨蝶呤的方案。移植后予鼻窦及颈部淋巴结区局部放疗,早期减停环孢素A和供者淋巴细胞输注防治复发。结果：患者移植后造血恢复顺利,中性粒细胞绝对数（ANC）〉0．5×10 9／L时间为＋13d,血小板〉20×10 9／L时间为＋15d。移植后未发生急性GVHD,发生肝脏及口腔的慢性GVHD,使用小剂量甲氨蝶呤和泼尼松后控制。随访至移植后8月余,造血功能恢复良好,病情处于持续完全缓解状态,仍在继续随访中。结论：allo-HSCT对NK／T细胞淋巴瘤可能是一种有效的根治方法,移植后的局部放疗及供者淋巴细胞输注能预防复发。

Abstract：

Objective： To explore the therapeutic effect of allogeneic hematopoietic stem cell transplantation （allo HSCT） for NK/T cell lymphoma. Methods： One patient with NK/T-cell lymphoma received allo-HSCT. The patient received conditioning regimens of improved busulfan/cyclophosphamide and relative HLA-identical peripheral blood stem cell transplantation. Graft versus host disease （GVHD） prophylaxis consisted of cyclosporin-A （CsA） and short course of methotrerate. The sinus and cervical lymph node area were received local ra diotherapy, and it followed by early cyclosporine tapering and donor lymphocyte infusion to prevent relapse after allo HSCT. Results： The hematopoietic stem cell was transplanted successfully. The ANC and PLT were grafted respectively in ＋ 13d and ＋ 15d. None of the acute GVHD was observed. The chronic GVHD involved liver and oral after transplantation, and it was controlled by low dose of methotrerate and prednisone. The patient was followed up for 8 months after allo-HSCT, and the state of illness retained continuous complete remission. Conclusions： Treatment of allo-HSCT was an effective radical cure for NK/T-cell lymphoma, and local radio therapy and donor lymphocyte infusion were used to prevent relapse post transplant.     

Outcome of allogeneic hematopoietic stem cell transplantation in adult patients with acute myeloid leukemia harboring trisomy 8

Trisomy 8 (+8) is one of the most common cytogenetic abnormalities in adult patients with acute myeloid leukemia (AML). However, the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in adult patients with AML harboring +8 remains unclear. To evaluate, the outcome and prognostic factors in patients with AML harboring +8 as the only chromosomal abnormality or in association with other abnormalities, we retrospectively analyzed the Japanese registration data of 631 adult patients with AML harboring +8 treated with allogeneic HSCT between 1990 and 2013. In total, 388 (61%) patients were not in remission at the time of HSCT. With a median follow-up of 38.5 months, the probability of overall survival and the cumulative incidence of relapse at 3 years were 40 and 34%, respectively. In the multivariate analysis, two or more additional cytogenetic abnormalities and not being in remission at the time of HSCT were significantly associated with a higher overall mortality and relapse. Nevertheless, no significant impact on the outcome was observed in cases with one cytogenetic abnormality in addition to +8. Although more than 60% of the patients received HSCT when not in remission, allogeneic HSCT offered a curative option for adult patients with AML harboring +8.