Total Body Irradiation-Based Conditioning Regimen Improved the Survival of Adult Patients With T-Cell Lymphoblastic Lymphoma After Allogeneic Peripheral Blood Stem Cell Transplantation.
ABSTRACT: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the consolidation modalities for adult patients with T-cell lymphoblastic lymphoma (T-LBL). However, the optimal conditioning regimen needs to be explored. In the present study, 40 patients with T-LBL undergoing allo-HSCT were retrospectively analyzed, including 23/40 (57.5%) with total body irradiation (TBI)-based conditioning regimen and 17/40 (42.5%) with busulfan (BU)-based regimen. TBI-based regimen significantly increased the cumulative incidence (CI) of grade II to IV acute graft-versus-host disease (aGvHD) as compared with BU-based regimen (13.0% vs 0%, P = 0.000). The relapse risk was significantly lowered in TBI-based group with a 2-year CI of relapse (CIR) of 9.1% as compared with that of 49.6% in BU-based group (P = 0.008). The 1-year and 2-year non-relapse mortalities (NRMs) for all patients were 5.0% and 10.3%, respectively. The 1-year and 2-year NRMs were 8.9% and 16.0% in TBI-based group, and 0.00% and 0.00% in BU-based group (P = 0.140). The 2-year probabilities of overall survival (OS) and relapse-free survival (RFS) were 83.0% [95% confidence interval, 63.4%-100%] and 74.0% (95% confidence interval, 54.4%-93.6%) in TBI-based group, which were higher than that of 35.0% (95% confidence interval, 0.0%-72.2%) and 50.0% (95% confidence interval, 24.5%-75.4%) in BU-based group, respectively (P = 0.020 for OS and P = 0.081 for RFS). In multivariate analysis, TBI-based regimen significantly reduced the risk of relapse [subdistribution hazard ratio (SHR) = 0.030, 95% CI, 0.002-0.040, P = 0.000] and improved the OS [hazard ratio (HR) 0.121, 95% CI, 0.021-0.683, P = 0.017] as an independent prognostic factor. These results suggested that TBI-based regimen might be an optimal choice for adult patients with T-LBL undergoing allo-HSCT.
Project description:Conventional myeloablative conditioning (MAC) regimens often cause severe regimen-related toxicity (RRT). Furthermore, many patients suffer from poor quality of life in accordance with the increase in long-term survivors. We therefore devised a reduced-toxicity myeloablative conditioning (RTMAC) regimen consisting of 8-Gy total body irradiation (TBI), fludarabine (FLU) and cyclophosphamide (CY) for pediatric hematological malignancies. A retrospective single-center analysis was performed on patients with leukemia or myelodysplastic syndrome (MDS), aged ≤20 years, who had received an 8-Gy TBI/FLU/CY RTMAC regimen followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thirty-one patients underwent first allo-HSCT after an RTMAC regimen. The diagnoses were acute lymphoblastic leukemia (n = 11), acute myeloid leukemia (n = 13), MDS (n = 4), juvenile myelomonocytic leukemia (n = 1) and acute leukemias of ambiguous lineage (n = 2). While 3 patients showed early hematological relapse, the remaining 28 patients achieved engraftments. None of the patients developed grade 4 or 5 toxicities during the study period. The 5-year overall survival and relapse-free survival were 80% [95% confidence interval: CI, 61-91%] and 71% [95% CI, 52-84%], respectively. Our RTMAC regimen would be less toxic and offers a high probability of survival for children with hematological malignancies.
Project description:To study the prognostic factors of adult patients with T-lymphoblastic lymphoma (T-LBL) and to evaluate therapeutic effects of acute lymphoblastic leukemia (ALL)-type chemotherapy in combination with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients who achieved overall response (OR) with first line ALL-type chemotherapy.This was a retrospective study of 59 adult patients with T-LBL treated with hyper-fractionated administration of cyclophosphamide, vincristine, doxorubicin and dexamethasone/methotrexate (hyper-CVAD/MA) chemotherapy alone or in combination with allo-HSCT between June 2008 and October 2015. Complete response (CR) and OR rates were evaluated after the initial chemotherapy. Clinical characteristics and the risk factors associated with prognosis and overall survival (OS) were analyzed in all patients and the effects of allo-HSCT on OS were evaluated in patients who had achieved OR after initial chemotherapy.Forty-eight patients (81.4%) achieved OR by hyper-CVAD chemotherapy, among which, 22 patients (45.8%) further received allo-HSCT. The median follow-up was 31.5 months, ranging from 11 to 97 months. The 3-year OS and progression-free survival (PFS) were 45.7% and 45.0% for patients who achieved OR after chemotherapy and both 0 for patients who did not achieve OR (both P?<?.001). Three year OS and PFS were higher in patients who received chemotherapy + allo-HSCT than in patients who received chemotherapy alone (3-year OS: 72.8% vs 17.5%, P?=?.008; PFS: 65.1% vs 27.8%, P?=?0.007). Shorter survival was independently associated with elevated lactic dehydrogenase (LDH), Ki-67?75%, pleural effusion and no OR (all P?<?.05) in all patients. But shorter survival was only associated with elevated LDH level, leukocytosis (>10 G/L), and chemotherapy alone in patients who achieved OR (all P?<?.05).The mid-term outcomes of adult patients with T-LBL are associated with response to chemotherapy (in all patients) and performance of allo-HSCT (in patients who achieved OR). Allo-HSCT could be a feasible and effective consolidation therapy for adult T-LBL.
Project description:A head-to-head comparison of outcomes of unrelated donor allogeneic peripheral blood stem cell transplantation for AML between reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) regimens using thymoglobulin for GVHD prophylaxis is limited. We evaluated outcomes of 122 AML patients who received either busulfan (Bu)/fludarabine (Flu)/low-dose total body irradiation (TBI) as RIC (n = 64, 52%) or Bu/Flu as MAC (n = 58, 48%), and thymoglobulin 4.5 mg/kg total dose between day - 3 to - 1 for GVHD prophylaxis. Grades III-IV acute GVHD (aGVHD) was lower with Bu/Flu/TBI compared with Bu/Flu (6.2% vs 26.1%, p = 0.009). At 1 year, Bu/Flu/TBI was associated with similar chronic GVHD (41.2% vs 44.8%, p = 0.75), OS (61.9% vs 56.9%, p = 0.69), relapse rate (29.9% vs 20.7%, p = 0.24), relapse-free survival (52.8% vs 50%, p = 0.80), non-relapse mortality (17.4% vs 29.3%, p = 0.41), and GVHD-free relapse-free survival (24.2% vs 27.5%, p = 0.80) compared with Bu/Flu. Multivariable analysis did not reveal any difference in outcomes between both regimens. In summary, thymoglobulin at 4.5 mg/kg did not have any adverse impact on survival when used with RIC regimen. Both Bu/Flu/TBI and Bu/Flu conditioning regimens yielded similar survival.
Project description:Relapse is common after hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia (ALL). Although 1200 cGy total body irradiation (TBI) and cyclophosphamide (Cy) is the standard conditioning regimen, attempts to reduce relapse have led to the addition of a second chemotherapeutic agent and/or higher dose of TBI. We examined HSCT outcomes in patients age <18 years with ALL, in second or subsequent remission or in relapse at transplantation. Most transplantations were performed with the patient in remission. Patients received grafts from an HLA-matched sibling or unrelated donor. Four treatment groups were created: (1) Cy + TBI ? 1200 cGy (n = 304), (2) Cy + etoposide + TBI ? 1200 cGy (n = 108), (3) Cy + TBI ? 1300 cGy (n = 327), and (4) Cy + etoposide + TBI ? 1300 cGy (n = 26). Neither TBI > 1200 cGy nor the addition of etoposide resulted in fewer relapses. The 5-year probability of relapse was 30% for group 1, 28% for group 2, 35% for group 3, and 31% for group 4. However, transplantation-related mortality was higher (35% versus 25%, P = .02) and overall survival lower (36% versus 48%, P = .03) in group 4 compared with group 3. Our findings indicate that compared with the standard regimen, neither TBI > 1200 cGy nor the addition of etoposide improves survival after HSCT for ALL.
Project description:Cyclophosphamide (Cy) in combination with busulfan (Bu) or total body irradiation (TBI) is the most commonly used myeloablative conditioning regimen in patients with chronic myeloid leukemia (CML). We used data from the Center for International Bone Marrow Transplantation Research to compare outcomes in adults who underwent hematopoietic cell transplantation for CML in first chronic phase after myeloablative conditioning with Cy in combination with TBI, oral Bu, or intravenous (i.v.) Bu. Four hundred thirty-eight adults received human leukocyte antigen (HLA)-matched sibling grafts and 235 received well-matched grafts from unrelated donors (URD) from 2000 through 2006. Important differences existed between the groups in distribution of donor relation, exposure to tyrosine kinase inhibitors, and year of transplantation. In multivariate analysis, relapse occurred less frequently among patients receiving i.v. Bu compared with TBI (relative risk [RR], .36; P = .022) or oral Bu (RR, .39; P = .028), but nonrelapse mortality and survival were similar. A significant interaction was detected between donor relation and the main effect in leukemia-free survival (LFS). Among recipients of HLA-identical sibling grafts, but not URD grafts, LFS was better in patients receiving i.v. Bu (RR, .53; P = .025) or oral Bu (RR, .64; P = .017) compared with TBI. In CML in first chronic phase, Cy in combination with i.v. Bu was associated with less relapse than TBI or oral Bu. LFS was better after i.v. or oral Bu compared with TBI.
Project description:Reduced-intensity conditioning (RIC) allogeneic haematopoietic cell transplantation (allo-HCT) is a curative option for select relapsed/refractory Hodgkin lymphoma (HL) patients; however, there are sparse data to support superiority of any particular conditioning regimen. We analyzed 492 adult patients undergoing human leucocyte antigen (HLA)-matched sibling or unrelated donor allo-HCT for HL between 2008 and 2016, utilizing RIC with either fludarabine/busulfan (Flu/Bu), fludarabine/melphalan (Flu/Mel140) or fludarabine/cyclophosphamide (Flu/Cy). Multivariable regression analysis was performed using a significance level of <0·01. There were no significant differences between regimens in risk for non-relapse mortality (NRM) (P = 0·54), relapse/progression (P = 0·02) or progression-free survival (PFS) (P = 0·14). Flu/Cy conditioning was associated with decreased risk of mortality in the first 11 months after allo-HCT (HR = 0·28; 95% CI = 0·10-0·73; P = 0·009), but beyond 11 months post allo-HCT it was associated with a significantly higher risk of mortality, (HR = 2·46; 95% CI = 0·1.32-4·61; P = 0·005). Four-year adjusted overall survival (OS) was similar across regimens at 62% for Flu/Bu, 59% for Flu/Mel140 and 55% for Flu/Cy (P = 0·64), respectively. These data confirm the choice of RIC for allo-HCT in HL does not influence risk of relapse, NRM or PFS. Although no OS benefit was seen between Flu/Bu and Flu/Mel 140; Flu/Cy was associated with a significantly higher risk of mortality beyond 11 months from allo-HCT (possibly due to late NRM events).
Project description:Given age-related differences in drug metabolism and indications for hematopoietic SCT (HSCT), personalized drug dosing of the conditioning regimen and post-transplant immunosuppression may reduce graft rejection, relapse rates and toxicity in pediatric HSCT recipients. This manuscript summarizes the pharmacokinetic/dynamic data of HSCT conditioning and post-grafting immunosuppression, presented at the First Annual Pediatric Bone Marrow Transplant Consortium (PBMTC) meeting in April 2013. Personalized dosing of BU to a target plasma exposure reduces graft rejection in children and improves relapse/toxicity rates in adults. Current weight-based dosing achieves the target BU exposure in only a minority (24.3%) of children. The initial BU dose should be based on the European Medicines Agency nomogram or population pharmacokinetic models to improve the numbers of children achieving the target exposure. There are limited pharmacokinetic data for treosulfan, CY, fludarabine and alemtuzumab as HSCT conditioning in children. For post-grafting immunosuppression, mycophenolic acid (MPA) clearance may be increased in younger children (<12 years). The preferred MPA pharmacokinetic monitoring parameters and target range are still evolving in HSCT recipients. Multi-institutional trials incorporating properly powered pharmacokinetic/dynamic studies are needed to assess the effect of variability in the plasma exposure of drugs/metabolites on clinical outcomes in pediatric HSCT recipients.
Project description:Intestinal microbiota (IM) diversity and composition regulates host immunity and affects outcomes after allogeneic stem cell transplantation (allo-HSCT). We evaluated if the oral mucosa microbiota (OM) could impact the outcomes in patients who underwent allo-HSCT. Samples from the oral mucosa of 30 patients were collected at three time points: before the conditioning regimen, at aplasia, and at engraftment. We analyzed the associations of OM diversity and composition with allo-HSCT outcomes. Lower OM diversity at preconditioning was associated with a higher risk of relapse at 3 years (68% versus 33%, respectively; P = 0.04). Dominance (relative abundance ≥ 30%) by a single genus at preconditioning was also associated with a higher risk of relapse (63% versus 36% at 3 years, respectively; P = 0.04), as well as worse progression-free survival (PFS; 19% versus 55%, respectively; P = 0.01), and overall survival (OS) at 3 years (38% versus 81%, respectively; P = 0.02). In our study we observed that OM dysbiosis is associated with a higher risk of relapse and worse survival after allo-HSCT.
Project description:<h4>Background</h4>There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.<h4>Methods</h4>From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n = 72) or allo-HSCT (n = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.<h4>Results</h4>Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).<h4>Conclusions</h4>Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.
Project description:Tyrosine kinase inhibitors (TKIs) have changed the indications for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia (CML). Therefore, we aimed to evaluate the effect of TKIs on allo-HSCT in CML.In this quasi-experimental study, we compared patient, disease, and transplantation characteristics as well as allo-HSCT outcomes between the pre-TKI era (before 2002) and the post-TKI era (2002 and later) in patients with CML. A total of 193 allo-HSCTs were performed between 1989 and 2012.Patients in the post-TKI era had more advanced disease (>chronic phase 1) at the time of transplant and more frequently received reduced-intensity conditioning compared to patients in the pre-TKI era. Relapse/progression occurred more frequently in the year ≥2002 group than in the year <2002 group (48% vs. 32% at 5 years, p=0.01); however, overall survival (OS) was similar in these two groups (5-year survival was 50.8% vs. 59.5%, respectively; p=0.3). TKIs (with donor lymphocyte infusions or alone) for treatment of relapse after allo-HSCT were available in the post-TKI era and were associated with improved OS. While the rates of hematologic remission at 3 months after allo-HSCT were similar between TKI eras, patients having remission had better disease-free survival (DFS) [relative risk (RR): 0.15, confidence interval (CI) 95%: 0.09-0.24, p<0.001] and OS (RR: 0.14, CI 95%: 0.09-0.23, p<0.001). Male allo-HSCT recipients had worse DFS (RR: 1.7, CI 95%: 1.2-2.5, p=0.007) and OS (RR: 1.7, CI 95%: 1.1-2.6, p=0.02) than females.TKIs are an effective option for the treatment of relapse after allo-HSCT in CML. Hematologic remission after allo-HSCT is also an important factor for survival in CML patients.