Favorable Outcome After Adjuvant Involved-Field Radiotherapy After Autologous Hematopoietic Stem-Cell Transplantation in Patients With High-Risk Relapsed/Refractory Lymphoma: A Single-Center Experience

BackgroundPatients with refractory or relapsed lymphoma diagnosed with bulky disease at relapse or with residual disease after salvage treatment are considered to have a dismal outcome, even after autologous hematopoietic stem-cell transplantation, as a result of disease recurrence. To minimize the risk of relapse after receipt of a transplant, involved-field radiotherapy (IFRT) to sites of either bulky or localized residual disease has been utilized; however, the ideal timing for irradiation remains controversial. The aim of this study was to assess the safety and efficacy of IFRT in the early period after transplantation.Patients and MethodsWe retrospectively evaluated the outcome of 24 autografted patients with relapsed/refractory lymphoma who presented with bulky disease at relapse or who had a persistent localized residual mass after salvage treatment and consolidated with IFRT within 4 months after autografting.ResultsNo significant toxicity was noticed during the early postradiotherapy period, while graft function was not impaired. After a median follow-up of 3 years for survivors, 21 patients were alive, 19 of whom were event free, while 2 patients died of disease recurrence and 1 died of treatment-related myelodysplastic syndrome. The 3-year overall, lymphoma relapse-free, and event-free survival rates were 86%, 86%, and 82%, respectively.ConclusionTaking into consideration the poor-risk features of the study cohort, IFRT provided early after autologous hematopoietic stem-cell transplantation showed a safe and well-tolerated toxicity profile and demonstrated long-term effective tumor control, as reflected in the promising survival rates.     

The Role of Low-dose Anti-thymocyte Globulin as Standard Prophylaxis in Mismatched and Matched Unrelated Hematopoietic Peripheral Stem Cell Transplantation for Hematologic Malignancies

IntroductionAnti-thymocyte globulin (ATG)-based immunosuppressive therapy is often used in allogeneic hematopoietic cell transplantation to reduce incidence and severity of graft-versus-host disease (GVHD).Patients and MethodsIn our observational study, ATG (rabbit, Thymoglobulin; Sanofi, 5 mg/kg) was administered as a standardized part of the conditioning in 97 patients with a median age of 34 years (range, 14-58 years), allotransplanted for hematologic malignancies from matched (8/8; n = 52) and allele or antigen mismatched (7/8; n = 43 and 6/8; n = 2) unrelated donors.ResultsFive-year overall survival (OS) was 46.9%, disease-free survival was 46.5%, and treatment-related mortality was 20.6%, with a median follow-up of 29 months (range, 1-145 months). Acute GVHD (grade ≥ II) cumulative incidence was 26.9% in matched versus 50.5% in mismatched patients (P = .060), whereas extensive chronic GVHD was 45.6% versus 50%, respectively (P = .310). Five-year OS was 62.2% for the matched patients and 27.9% for the mismatched patients (P = .003) owing to a higher treatment-related mortality rate in mismatched patients (P = .032). In multivariate analysis including age, gender, time until transplantation, disease phase, mismatched donor, ABO mismatch, number of CD34+ infused, acute and chronic GVHD, the significant unfavorable factors for OS were HLA mismatch and advanced disease phase.ConclusionA relatively low-dose ATG is effective in acute GVHD prophylaxis, leading to promising survival rates in matched transplants. Further comparative studies with adjusted ATG dose depending on Human leukocyte antigen disparity or alternative donors are warranted.     

含氟达拉滨的预处理行异基因造血干细胞移植治疗恶性血液病的远期疗效

目的：观察含氟达拉滨的预处理方案进行异基因造血干细胞移植治疗恶性血液病的长期疗效。方法：选取2003年2 月至2004年12月间厦门大学附属中山医院收治的15例恶性血液病患者,其中急性髓性白血病3 例,急性淋巴细胞白血病5 例,慢性粒细胞白血病6 例,骨髓增生异常综合症（RAEB）1 例。供受者HLA 配型同胞全相合6 例,同胞或亲缘不相合8 例,非亲缘全相合1 例。预处理方案采用氟达拉滨（Flu 30mg/m2·d,共5d）、马利兰（BU4mg/kg·d,共2～3d）、环磷酰胺（CTX 50mg/kg·d,共2d）,其中8 例加用阿糖胞苷（Ara-c 1.0～2.0g/m2·d,共2d）,9 例HLA 不全相合及非血缘移植者加用兔抗胸腺细胞球蛋白（ATG 3.0～5.0mg/kg·d,共3d）。 预防移植物抗宿主病（GVHD）均采用骁悉（MMF）+ 环孢素（CsA）+ 短程甲氨喋呤（MTX）方案。利用SPSS11.5 统计软件及Kaplan-Meier 方法进行生存分析。结果：15例患者移植后均获得快速完全的植入,无严重的预处理相关毒性。46.7% 发生急性GVHD ,85.7% 发生慢性GVHD ;带状疱疹7.1% 。5 年总生存率为53.5% ,其中移植时处于第一次完全缓解（CR1）和慢性期患者11例,5 年生存率为72.7% ,复发率9.1% ,移植时处于第二次完全缓解（CR2）、复发、加速期及急变期的患者4 例,2 年生存率为0,复发率75,两者有统计学差异（P=0.000 3 和P<0.05）,主要死亡原因为疾病复发和GVHD 。结论：对于移植时处于CR1 和慢性期患者,采用含Flu并适当减低放化疗剂量的预处理方案是有效的移植预处理方案,毒副作用较少,未增加机会性感染,复发率较低;预处理中加入Flu对GVHD 发生率无明显影响。     

异基因造血干细胞移植FBC预处理14例

[目的]探讨FBC预处理方案在异基因造血干细胞移植中的可行性.[方法]以FBC预处理对14例恶性血液病患者进行异基因造血干细胞移植.FBC预处理方案组成:磷酸氟达拉滨30mg/(m2·d),静滴,-5d～-1d;白消安0.6mg/(kg·d),口服,q6h,-7d～-4d;环磷酰胺30 mg/(kg·d),静滴,-3d～-2d.[结果]14例患者移植后均安全通过骨髓抑制期,顺利重建造血功能,白细胞升至1×109/L为 11d( 9d～ 15d),血小板上升至20×109/L为 12d( 9d～ 21d).8例(57.1%)出现急性移植物抗宿主病,5例(35.7%)出现慢性移植物抗宿主病.至今仍存活11例(78.6%),3例(21.4%)死亡.[结论]用FBC预处理方案进行异基因造血干细胞移植治疗恶性血液病安全、有效.     

Graft-Versus-Host Disease in Multiple Myeloma Patients Treated With Daratumumab After Allogeneic Transplantation

IntroductionAllogeneic hematopoietic cell transplantation (allo-HCT) represents an adoptive immunotherapy strategy for eliciting a graft-versus-myeloma, the effect for high-risk or relapsed multiple myeloma (MM). Allo-HCT recipients are at risk for graft-versus-host disease (GVHD) as well as associated increases in morbidity and mortality. Daratumumab, an anti-CD38 human immunoglobulin G1 kappa humanized monoclonal antibody, is used for treatment of MM. Daratumumab also affects CD38⁺ nonmyeloma cells, including T cells, which mediate GVHD. The use of daratumumab after allo-HCT has not been well described, and its potential impact on GVHD is unknown.Patients and MethodsIn a multicenter retrospective study, we evaluated incidence of GVHD in 34 patients with relapsed MM treated with daratumumab after allo-HCT.ResultsOverall response to daratumumab (partial response or better) was 41% (95% confidence interval, 24-59). Five patients (15%) developed acute GVHD after daratumumab therapy; no chronic GVHD events were observed after daratumumab therapy. One of these 5 patients had a history of chronic GVHD and developed a flare of acute GVHD during daratumumab therapy. The remaining 4 patients did not have a history of GVHD before daratumumab.ConclusionThe incidence of GVHD after daratumumab was low and did not result in increased exacerbation of GVHD in patients with a history of GVHD.     

Immune Reconstitution of CD4+T Cells after Allogeneic Hematopoietic Stem Cell Transplantation and its Correlation with Invasive Fungal Infection in Patients with Hematological Malignancies

Objective: To explore the immune reconstitution of CD4+T cells after allogeneic hematopoietic stem celltransplantation (Allo-HSCT) and its relationship with invasive fungal infection (IFI) in patients with hematologicalmalignancies. Materials and Methods: Forty-seven patients with hematological malignancies undergoing Allo-HSCT in Binzhou Medical University Hospital from February, 2010 to October, 2014 were selected. At 1, 2and 3 months after transplantation, the immune subpopulations and concentration of cytokines were assessedrespectively using flow cytometry (FCM) and enzyme linked immunosorbent assay (ELISA). The incidenceof IFI after transplantation and its correlation with immune reconstitution of CD4+T cells were investigated.Results: The number of CD4+T cells and immune subpopulations increased progressively after transplantationas time went on, but the subpopulation cell count 3 months after transplantation was still significantly lowerthan in the control group (p<0.01). In comparison to the control group, the levels of interleukin-6 (IL-6) andIL-10 after transplantation rose evidently (p<0.01), while that of transforming growth factor-β (TGF-β) wasdecreased (p<0.01). There was no statistically significant difference level of interferon-γ (IFN-γ) (p>0.05). Theincidence of IFI was 19.2% (9/47), and multivariate logistic regression revealed that IFI might be related toTh17 cell count (p<0.05), instead of Th1, Th2 and Treg cell counts as well as IL-6, IL-10, TGF-β and IFN-γlevels (p>0.05). Conclusions: After Allo-HSCT, the immune reconstitution of CD4+T cells is delayed and Th17cell count decreases obviously, which may be related to occurrence of IFI.     

Impact of Blood Count Recovery-based Complete Remission Before Allogeneic Hematopoietic Stem Cell Transplantation on Survival in Patients With Acute Myeloid Leukemia

BackgroundPatients who achieve complete remission (CR) with incomplete blood count recovery (CRi) in acute myeloid leukemia (AML) have inferior overall survival and lower progression-free survival. The aim of this study was to define whether blood count recovery-based CR before allogeneic hematopoietic stem cell transplantation (alloHSCT) had an impact on survival in patients with AML.Materials and MethodsThis study has been performed in a retrospective manner. One hundred one patients with AML who received an alloHSCT in our transplant center at Hacettepe University Hospital between the years 2001 and 2018 were evaluated. CRi were defined as bone marrow CR with absolute neutrophil count < 1000/mm³ and/or platelet count < 100.000/mm³. CR and CRi were confirmed just before alloHSCT in bone marrow and peripheral blood, respectively.ResultsA total of 101 patients were entered into the study between 2001 and 2018. Median follow-up for all survivors was 38 months (range, 6-220 months). The 5-year overall survival for patients who were in CRi and patients who were in CR before transplantation were 58% and 67%, respectively (P = .68). The 5-year progression-free survival for patients who were in CRi and patients who were in CR before transplantation were 68% and 64%, respectively (P = .99).ConclusionIn conclusion, we observed equivalent posttransplant outcomes between patients who were in CR and patients who were in CRi before alloHSCT. We assume that alloHSCT eliminated the negative effect of pre-transplant blood count levels.     

Clinical Outcomes of Fludarabine and Melphalan With an 800 cGy Total Body Irradiation Conditioning Regimen in Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

IntroductionAllogeneic hematopoietic stem cell transplant with reduced-intensity conditioning is an effective therapeutic option for patients with refractory or relapsed aggressive non-Hodgkin lymphoma (NHL).Patients and MethodsWe retrospectively evaluated survival outcomes and the efficacy of our fludarabine/melphalan/total body irradiation (TBI) (FMT) regimen. A total of 89 patients had received the FMT regimen from 2007 to 2017.ResultsThe majority of patients (n = 81; 91%) belonged to the histologic subtype of aggressive NHL. The estimated 3-year overall survival and disease-free survival for the entire cohort during a median follow-up of 31 months were 47.1% (95% confidence interval, 36%-57%) and 45.4% (95% confidence interval, 35%-56%), respectively. The cumulative incidence rates of relapse and non-relapse mortality at 3 years were 33.1% and 13.8%, respectively. In analyses of risk factors affecting survival outcomes, chemosensitive disease status at transplant (hazard ratio [HR], 2.45; P = .010), delayed relapse after first-line chemotherapy (HR, 2.101; P = .009), no grade III to IV acute graft-versus-host disease (HR, 11.212; P < .001), and mild chronic graft-versus-host disease (HR, 0.448; P = .016) were independent significant predictors of favorable overall survival. Also, similar parameters were related to favorable disease-free survival. All non-hematologic toxicities occurred within 50 days after allogeneic hematopoietic stem cell transplant, and most of the adverse events were tolerable and manageable with a < 30% incidence.ConclusionOur FMT regimen shows favorable transplant outcomes with relatively low-risk toxicities, so it may be a promising strategy for patients with relapsed or refractory aggressive NHL.     

A Comparison of Long-Term Outcomes of Donor Lymphocyte Infusions and Tyrosine Kinase Inhibitors in Patients With Relapsed CML After Allogeneic Hematopoietic Cell Transplantation

BackgroundDonor lymphocyte infusion (DLI) and tyrosine kinase inhibitors (TKIs) are the 2 standard treatment options in chronic myeloid leukemia (CML) that relapses after hematopoietic cell transplantation (HCT), but reports comparing long-term outcomes of these modalities are rare.Patients and MethodsA total of 46 patients were treated with either DLI (n = 28) or TKIs (n = 18) during a first relapse of CML after HCT between 1993 and 2012. The stage of relapse was the chronic phase in 37 patients and the advanced phase in 9 patients. All patients had myeloablative conditioning without T-cell depletion during HCT. The median interval between HCT and treatment for relapse was 34 (range, 2-197) months.ResultsAt a median follow-up of 146 and 70 months, respectively, 32% of the DLI group and 33% of the TKI group had died. Six (21%) patients initially treated with DLI received TKIs during a second relapse. In multivariable analyses, DLI was associated with inferior overall survival (OS) (hazard ratio [HR], 37.4; 95% confidence interval [CI], 2.2-625.4; P = .01), shorter failure-free survival (FFS) (HR, 21.15; 95% CI, 1.8-251; P = .02), higher cumulative incidence of failure (CIF) (HR, 19.5; 95% CI, 1.6-236.5; P = .02), and increased incidence of treatment-induced graft vs. host disease (GVHD) (68% vs. 6%; P = .001).ConclusionTKIs appear better than DLI in chronic-phase relapses after myeloablative non–T-cell-depleted HCT. Outcomes were poor in advanced-phase relapses irrespective of treatment modality.