Clinical spectrum, outcome and management of immune thrombocytopenia associated with myelodysplastic syndromes and chronic myelomonocytic leukemia.

Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are associated with systemic inflammatory or autoimmune diseases in 10-20 % of cases. Among them, immune thrombocytopenia (ITP) has been reported but large studies assessing this association are missing. Whether such patients have a particular phenotype and require particular management is unclear. This study analyzes the clinical spectrum, outcome and therapeutic management of patients with ITP associated with MDS or CMML, in comparison (i) to patients with primary ITP without MDS/CMML and (ii) to patients with MDS/CMML without ITP. Forty-one MDS/CMML-associated ITP patients were included, with chronic ITP in 26 (63%) patients, low-risk myelodysplasia in 30 (73%) patients and CMML in 24 (59%) patients. An associated autoimmune disease was noted in 10 (24%) patients. In comparison to primary ITP patients, MDS/CMML-associated ITP patients had a higher occurrence of severe bleeding despite similar platelet counts at diagnosis. First-line treatment consisted of glucocorticoids (98%) and intravenous immunoglobulin (IVIg) (56%). Response achievement with IVIg was more frequent in primary ITP than in MDS/CMML-associated ITP patients. Response rates to second-line therapies were not statistically different between primary ITP and MDS/CMMLassociated ITP patients. Ten percent (n=4) of patients with MDS/CMML-associated ITP had multirefractory ITP versus none in primary ITP controls. After a median follow-up of 60 months, there was no difference in overall survival between MDS/CMML-associated ITP and primary ITP patients. Leukemia-free-survival was significantly better in MDS/CMMLassociated ITP patients than in MDS/CMML without ITP MDS/CMML-associated ITP have a particular outcome with more severe bleeding and multirefractory profile than primary ITP, similar response profile to primary ITP therapy except for IVIg, and less progression toward acute myeloid leukemia than MDS/CMML without ITP.

Thiotepa, Busulfan, and Fludarabine Conditioning Regimen in T Cell-Replete HLA-Haploidentical Hematopoietic Stem Cell Transplantation.

We report the outcomes of 51 patients who underwent unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide (PT-Cy) and antithymocyte globulin (ATG), from peripheral blood stem cells (PBSCs) or bone marrow, after receipt of a TBF (thiotepa, busulfan, and fludarabine) conditioning regimen. Their median age was 55 years (range, 16 to 72 years). Hematologic diagnoses included acute leukemias (n = 31), lymphoid neoplasm (n = 12), myeloproliferative neoplasm (n = 5), and myelodysplastic syndromes (n = 3). Thirty-seven patients (73%) were in complete remission. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate for all patients, associated with ATG in 39 patients (76.5%). The median time to neutrophil engraftment was 17 days (range, 12 to 34 days). The cumulative incidences of grade II-IV and grade III-IV acute GVHD were 27.5% and 14%, respectively. In patients receiving a PBSC graft and ATG prophylaxis, grade II-IV aGVHD occurred in 16% of patients. The use of ATG and a lower thiotepa dose (5 mg/kg versus 10 mg/kg) were associated with a reduced cumulative incidence of grade II-IV acute GVHD (P = .03 and .005, respectively). The 2-year cumulative incidence of chronic GVHD was 29% and was significantly reduced to 13% with the lower thiotepa dose (P = .002). After a median follow-up of 25 months (range, 12 to 62 months), the cumulative incidences of nonrelapse mortality, relapse, overall survival (OS), disease-free survival (DFS), and GVHD-free, relapse-free survival (GFRFS) were 20%, 22.5%, 67%, 58%, and 51%, respectively. Pretransplantation disease status (complete remission versus others) was the main factor associated with OS, DFS, and GFRFS. In conclusion, the TBF conditioning regimen is an appealing platform in the haplo-HSCT setting with PT-Cy in terms of engraftment rate, toxicity, and disease control. We found no benefit of a thiotepa dose of 10 mg/kg compared with a dose of 5 mg/kg. ATG reduced the risk of acute GVHD without comprising outcomes.

Defibrotide for Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease Prophylaxis in High-Risk Adult Patients: A Single-Center Experience Study.

Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a serious complication after hematopoietic stem cell transplantation (HSCT). SOS/VOD usually occurs within 3 weeks of HSCT, but the 2016 European Society for Blood and Marrow Transplantation diagnosis criteria have been revised to include late forms. Prophylactic use of defibrotide is recommended in the pediatric setting, but its value remains uncertain in the adult population. We report here a single-center series of 63 adult patients considered at high risk for SOS/VOD who received defibrotide prophylaxis in combination with ursodeoxycholic acid between May 2012 and August 2016. The median duration of defibrotide therapy was 23 days. Bleeding occurred in 14 patients (21.5%). Defibrotide prophylaxis was discontinued in 7 patients (10.8%): 4 cases (6.3%) due to bleeding and 3 cases (4.6%) because of the need for antithrombotic therapy. Overall, SOS/VOD occurred in 4 cases (6.3%) within 21 days after HSCT (days 13 and 14) in 2 cases and late-onset SOS/VOD (days 57 and 58) in the other 2 cases. SOS/VOD was moderate in 1 case, very severe in 3 cases, with 2 deaths related to SOS/VOD. Cumulative incidence of grades II to IV acute graft-versus-host disease and transplant-associated thrombotic microangiopathy were 22.2% and 3.2%, respectively. With a median follow-up of 31 months (range, 10.7 to 60.3), the rates of 2-year overall survival, progression-free survival, incidence of relapse, and nonrelapse mortality were 56.5%, 49%, 28.7%, and 22.3%, respectively. In our experience defibrotide prophylaxis is associated with a low incidence of SOS/VOD after allogeneic HSCT in a high-risk adult population with an acceptable safety profile.

Azacitidine improves outcome in higher-risk MDS patients with chromosome 7 abnormalities: a retrospective comparison of GESMD and GFM registries.

Treatment with azacitidine (AZA) has been suggested to be of benefit for higher-risk myelodysplastic syndrome (HR-MDS) patients with chromosome 7 abnormalities (Abn 7). This retrospective study of 235 HR-MDS patients with Abn 7 treated with AZA (n = 115) versus best supportive care (BSC; n = 120), assessed AZA treatment as a time-varying variable in multivariable analysis. A Cox Regression model with time-interaction terms of overall survival (OS) at different time points confirmed that, while chromosome 7 cytogenetic categories (complex karyotype [CK] versus non-CK) and International Prognostic Scoring System risk (high versus intermediate-2) retained poor prognosis over time, AZA treatment had a favourable impact on OS during the first 3 years of treatment compared to BSC (Hazard ratio [HR] 0·5 P < 0·001 at 1 year, 0·7 P = 0·019 at 2 years; 0·73 P = 0·029 at 3 years). This benefit was present in all chromosome 7 categories, but tended to be greater in patients with CK (risk reduction of 82%, 68% and 53% at 1, 3 and 6 months in CK patients; 79% at 1 month in non-CK patients, P < 0·05 for all). AZA also significantly improved progression-free survival (P < 0·01). This study confirms a time-dependent benefit of AZA on outcome in patients with HR-MDS and cytogenetic abnormalities involving chromosome 7, especially for those with CK.

Efficacy and feasibility of sorafenib as a maintenance agent after allogeneic hematopoietic stem cell transplantation for Fms-like tyrosine kinase 3-mutated acute myeloid leukemia.

BACKGROUND: Sorafenib has shown encouraging results in patients with Fms-like tyrosine kinase 3 (FLT3)-positive acute myeloid leukemia. Its role after allogeneic stem cell transplantation (HSCT) has been reported in a few cases with encouraging results. METHODS: The authors describe the use of sorafenib as a maintenance agent after HSCT in 27 patients with FLT3-positive acute myeloid leukemia. RESULTS: The median age of the patients was 46 years (range, 15-57 years). Sorafenib was introduced at a median of 70 days (range, 29-337 days) after HSCT. The median treatment duration was 8.4 months (range, 0.2-46 months). Eleven patients experienced treatment toxicities, mainly of grade 1 to 2 (graded according to the National Cancer Institute Common Toxicity Criteria [version 4.0]). Dose reduction or withdrawal was required in 4 patients and 4 patients, respectively. The persistence of toxicity prompted treatment withdrawal in 1 patient. Clinical improvement followed dose modifications. Thirteen patients experienced chronic graft-versus-host disease (limited in 9 patients and extensive in 4 patients), resulting in dose reduction in 5 patients followed by withdrawal in 1 of these individuals. At a median follow-up of 18 months (range, 4-48 months), 25 patients were alive (all of whom were in complete molecular remission) and 18 were still receiving treatment, with 1-year overall survival and progression-free survival rates of 92% ± 6% and 92% ± 5%, respectively. CONCLUSIONS: Sorafenib treatment after HSCT appears to be feasible and highly effective with dose individualization according to patient tolerability. Further analysis is needed to evaluate the immunomodulating role of sorafenib after HSCT. The data from the current support prospective controlled trials of sorafenib after HSCT. Cancer 2017;123:2867-74. © 2017 American Cancer Society.

Precision and prognostic value of clone-specific minimal residual disease in acute myeloid leukemia.

The genetic landscape of adult acute myeloid leukemias (AML) has been recently unraveled. However, due to their genetic heterogeneity, only a handful of markers are currently used for the evaluation of minimal residual disease (MRD). Recent studies using multi-target strategies indicate that detection of residual mutations in less than 5% of cells in complete remission is associated with a better survival. Here, in a series of 69 AMLs with known clonal architecture, we design a clone-specific strategy based on fluorescent in situ hybridization and high-sensitivity next generation sequencing to detect chromosomal aberrations and mutations, respectively, in follow-up samples. The combination of these techniques allows tracking chromosomal and genomic lesions down to 0.5-0.4% of the cell population in remission samples. By testing all lesions in follow-up samples from 65 of 69 evaluable patients, we find that initiating events often persist and appear to be, on their own, inappropriate markers to predict short-term relapse. In contrast, the persistence of two or more lesions in more than 0.4% of the cells from remission samples is strongly associated with lower leukemia-free and overall survivals in univariate and multivariate analyses. Although larger prospective studies are needed to extend these results, our data show that a personalized, clone-specific, MRD follow up strategy is feasible in the vast majority of AML cases.

The strategy for the diagnosis of invasive pulmonary aspergillosis should depend on both the underlying condition and the leukocyte count of patients with hematologic malignancies.

The identification of the causative organism in invasive pulmonary aspergillosis (IPA) is recommended. We investigated whether a mycologic diagnostic strategy could be optimized based on patient characteristics. Fifty-five patients were enrolled in a prospective study. The presence of Aspergillus in respiratory samples occurred more frequently in non-acute leukemia (AL) patients than in AL patients (P = .0003), and in patients with leukocyte counts more than 100/mm(3) (P = .002). In a logistic regression model, these 2 factors appeared to be independent, with an adjusted odds ratio of 7.14 (95% confidence interval, 1.40-36.5) for non-AL patients and an adjusted odds ratio of 6.97 (95% confidence interval, 1.33-36.5) for patients with leukocyte counts more than 100/mm(3). A positive mycologic result was also more frequent among patients with lung CT scan signs of airway-invasive disease than among other patients (P = .043). Airway-invasive signs were more frequent among non-AL patients (P = .049), whereas angioinvasive disease was more frequent among both AL patients (P = .01) and patients with leukocyte counts less than 100/mm(3) (P = .001). A concomitant pulmonary infection was identified more frequently among non-AL patients (P = .005 vs allogeneic hematopoietic stem cell transplant and P = .048 vs others). Our results suggest that different strategies for diagnosing IPA should be considered based on the underlying condition.

Azacitidine in untreated acute myeloid leukemia: a report on 149 patients.

Limited data are available on azacitidine (AZA) treatment and its prognostic factors in acute myeloid leukemia (AML). One hundred and forty-nine previously untreated AML patients considered ineligible for intensive chemotherapy received AZA in a compassionate patient-named program. AML diagnosis was de novo, post-myelodysplastic syndromes (MDS), post-MPN, and therapy-related AML in 51, 55, 13, and 30 patients, respectively. Median age was 74 years, median white blood cell count (WBC) was 3.2 × 109 /L and 58% of the patients had ≥ 30% marrow blasts. Cytogenetics was adverse in 60 patients. Patients received AZA for a median of five cycles (range 1-31). Response rate (including complete remission/CR with incomplete recovery/partial remission) was 27.5% after a median of three cycles (initial response), and 33% at any time (best response). Only adverse cytogenetics predicted poorer response. Median overall survival (OS) was 9.4 months. Two-year OS was 51% in responders and 10% in non-responders (P<0.0001). Adverse cytogenetics, WBC >15 × 109 /L and ECOG-PS ≥ 2 predicted poorer OS, while age and marrow blast percentage had no impact. Using MDS IWG 2006 response criteria, among patients with stable disease, those with hematological improvement had no significant survival benefit in a 7 months landmark analysis. Outcomes observed in this high-risk AML population treated with AZA deserve comparison with those of patients treated intensively in prospective studies.

Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine.

Prognostic factors for response and survival in higher-risk myelodysplastic syndrome patients treated with azacitidine (AZA) remain largely unknown. Two hundred eighty-two consecutive high or intermediate-2 risk myelodysplastic syndrome patients received AZA in a compassionate, patient-named program. Diagnosis was RA/RARS/RCMD in 4%, RAEB-1 in 20%, RAEB-2 in 54%, and RAEB-t (AML with 21%-30% marrow blasts) in 22%. Cytogenetic risk was good in 31%, intermediate in 17%, and poor in 47%. Patients received AZA for a median of 6 cycles (1-52). Previous low-dose cytosine arabinoside treatment (P = .009), bone marrow blasts > 15% (P = .004), and abnormal karyotype (P = .03) independently predicted lower response rates. Complex karyotype predicted shorter responses (P = .0003). Performance status ≥ 2, intermediate- and poor-risk cytogenetics, presence of circulating blasts, and red blood cell transfusion dependency ≥ 4 units/8 weeks (all P < 10(-4)) independently predicted poorer overall survival (OS). A prognostic score based on those factors discriminated 3 risk groups with median OS not reached, 15.0 and 6.1 months, respectively (P < 10(-4)). This prognostic score was validated in an independent set of patients receiving AZA in the AZA-001 trial (P = .003). Achievement of hematological improvement in patients who did not obtain complete or partial remission was associated with improved OS (P < 10(-4)). In conclusion, routine tests can identify subgroups of patients with distinct prognosis with AZA treatment.

Administration of alemtuzumab and G-CSF to adults with relapsed or refractory acute lymphoblastic leukemia: results of a phase II study.

The outlook for adults with refractory and relapsed acute lymphocytic leukemia (ALL) is poor. CD52 is expressed in most patients with ALL. Alemtuzumab is an anti-CD52 humanized monoclonal antibody. This phase II study assessed the efficacy of alemtuzumab combined with granulocyte-colony stimulating factor (G-CSF) to boost antibody-dependent cell cytotoxicity mediated by neutrophils. Twelve patients with relapsed (n = 11) or refractory (n = 1) ALL, including four relapses postallogeneic stem cell transplantation, were treated and monitored between October 2006 and January 2011. Patients received 1 wk of alemtuzumab every other day at increasing doses of 3, 10, and 30 mg to test tolerance and 30 mg three times a week for 12-18 infusions. If in complete remission (CR), patients received maintenance therapy for 1 wk, every 2 months. G-CSF was administered at 5 µg/kg per day during alemtuzumab administration. The primary endpoint was disappearance of blast cells on a marrow aspirate. CD52 was expressed in all patients. Four patients reached CR. In one additional patient, clearance of blast cells was observed in peripheral blood but not in the marrow. The most frequent adverse events during course 1 of treatment were fever and chills (n = 3), skin rash (n = 3), and bronchospasm (n = 2). Tumor lysis syndrome was observed at treatment initiation in one patient who reached CR. All patients progressed within a few months and all but one died. The surviving patient is still alive after relapse and a second allogeneic stem cell transplantation. This study shows that in relapse/refractory ALL, alemtuzumab with G-CSF can produce good responses of short duration.

Prospective evaluation of clinical and biological markers to predict the outcome of invasive pulmonary aspergillosis in hematological patients.

Early evaluation of treatment efficacy in invasive aspergillosis (IA), a leading cause of morbidity and mortality in hematological patients, remains a challenge. We conducted a prospective study to evaluate the performance of different markers in predicting the outcome of patients with IA. Both clinical and biological criteria were assessed 7, 14, 21, and 45 days after inclusion in the study, and mortality was assessed at day 60. The association between baseline data and their evolution and the day 45 response to treatment was analyzed. A total of 57 patients (4 with proven, 44 with probable, and 9 with possible aspergillosis according to the revised EORTC/MSG [European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group] definitions) were included. At day 45, 30 patients (53%) were determined to be responders, 25 (44%) were nonresponders, and 2 were not able to be evaluated. Twenty patients died within the 60 days of follow-up. We found that a poor day 45 outcome was associated with patients who had high baseline serum galactomannan (GM) antigen levels and those receiving steroids at the time of IA. A consistently negative serum GM index was associated with a good outcome, and the day 14 clinical evaluation was predictive of the day 45 outcome. No association was found between Aspergillus antibodies or DNA detection and patients' outcome. We conclude that the GM index value at diagnosis of IA, GM index kinetics, and clinical evaluation at day 14 are good markers for predicting the outcome of patients with IA and should be taken into account for adapting antifungal treatment.

Germline ATG2B/GSKIP-containing 14q32 duplication predisposes to early clonal hematopoiesis leading to myeloid neoplasms.

The germline predisposition associated with the autosomal dominant inheritance of the 14q32 duplication implicating ATG2B/GSKIP genes is characterized by a wide clinical spectrum of myeloid neoplasms. We analyzed 12 asymptomatic carriers and 52 patients aged 18-74 years from six families, by targeted sequencing of 41 genes commonly mutated in myeloid malignancies. We found that 75% of healthy carriers displayed early clonal hematopoiesis mainly driven by TET2 mutations. Molecular landscapes of patients revealed two distinct routes of clonal expansion and leukemogenesis. The first route is characterized by the clonal dominance of myeloproliferative neoplasms (MPN)-driver events associated with TET2 mutations in half of cases and mutations affecting splicing and/or the RAS pathway in one-third of cases, leading to the early development of MPN, mostly essential thrombocythemia, with a high risk of transformation (50% after 10 years). The second route is distinguished by the absence of MPN-driver mutations and leads to AML without prior MPN. These patients mostly harbored a genomic landscape specific to acute myeloid leukemia secondary to myelodysplastic syndrome. An unexpected result was the total absence of DNMT3A mutations in this cohort. Our results suggest that the germline duplication constitutively mimics hematopoiesis aging by favoring TET2 clonal hematopoiesis.

Analysis of the ten-eleven translocation 2 (TET2) gene in familial myeloproliferative neoplasms.

The JAK2(V617F) mutation does not elucidate the phenotypic variability observed in myeloproliferative neoplasm (MPN) families. A putative tumor suppressor gene, TET2, was recently implicated in MPN and myelodysplastic syndromes through the identification of acquired mutations affecting hematopoietic stem cells. The present study analyzed the TET2 gene in 61 MPN cases from 42 families. Fifteen distinct mutations were identified in 12 (20%) JAK2(V617F)-positive or -negative patients. In a patient with 2 TET2 mutations, the analysis of 5 blood samples at different phases of her disease showed the sequential occurrence of JAK2(V617F) and TET2 mutations concomitantly to the disease evolution. Analysis of familial segregation confirmed that TET2 mutations were not inherited but somatically acquired. TET2 mutations were mainly observed (10 of 12) in patients with primary myelofibrosis or patients with polycythemia vera or essential thrombocythemia who secondarily evolved toward myelofibrosis or acute myeloid leukemia.

Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients.

Acute myeloid leukemia (AML) intensive chemotherapy combined with broad-spectrum antibiotics, leads to gut microbiota dysbiosis promoting pathological conditions and an increased incidence of complications. Here we report findings from a phase II single-arm, multicenter study evaluating autologous fecal microbiota transfer (AFMT) in 25 AML patients treated with intensive chemotherapy and antibiotics (ClinicalTrials.gov number: NCT02928523). The co-primary outcomes of the study are to evaluate the efficacy of AFMT in dysbiosis correction and multidrug-resistant bacteria eradication. The main secondary outcomes are to define a dysbiosis biosignature, to evaluate the effect of dysbiosis correction on patient clinical status, to assess the short and mid-term safety of AFMT in this immunocompromised population, and to evaluate the feasibility of the AFMT procedure and acceptability by the patient. Intensive induction chemotherapy induces a dramatic decrease of α-diversity indices, and a microbial dysbiosis with a significant shift of the microbial communities and domination of pro-inflammatory families. After AFMT treatment, α-diversity indices return to their initial mean levels and the similarity index shows the restoration of microbial communities. The trial meets pre-specified endpoints. AFMT appears to be safe and may be effective for gut microbiota restoration in AML patients receiving intensive chemotherapy and antibiotics, with an excellent gut microbiota reconstruction based on both richness and diversity indices at the species level.

Early Cardiac Toxicity Associated With Post-Transplant Cyclophosphamide in Allogeneic Stem Cell Transplantation.

BACKGROUND: Post-transplant cyclophosphamide (PT-Cy) has become a standard of care in haploidentical hematopoietic stem cell transplantation (HSCT) to reduce the risk of graft-versus-host disease. However, data on cardiac events associated with PT-Cy are scarce. OBJECTIVES: This study sought to assess the incidence and clinical features of cardiac events associated with PT-Cy. METHODS: The study compared clinical outcomes between patients who received PT-Cy (n = 136) and patients who did not (n = 195), with a focus on early cardiac events (ECE) occurring within the first 100 days after HSCT. All patients had the same systematic cardiac monitoring. RESULTS: The cumulative incidence of ECE was 19% in the PT-Cy group and 6% in the no-PT-Cy group (p < 0.001). The main ECE occurring after PT-Cy were left ventricular systolic dysfunction (13%), acute pulmonary edema (7%), pericarditis (4%), arrhythmia (3%), and acute coronary syndrome (2%). Cardiovascular risk factors were not associated with ECE. In multivariable analysis, the use of PT-Cy was associated with ECE (hazard ratio: 2.7; 95% confidence interval: 1.4 to 4.9; p = 0.002]. Older age, sequential conditioning regimen, and Cy exposure before HSCT were also associated with a higher incidence of ECE. Finally, a history of cardiac events before HSCT and ECE had a detrimental impact on overall survival. CONCLUSIONS: PT-Cy is associated with a higher incidence of ECE occurring within the first 100 days after HSCT. Patients who have a cardiac event after HSCT have lower overall survival. These results may help to improve the selection of patients who are eligible to undergo HSCT with PT-Cy, especially older adult patients and patients with previous exposure to Cy.

Fractionated gemtuzumab ozogamicin in association with high dose chemotherapy: a bridge to allogeneic stem cell transplantation in refractory and relapsed acute myeloid leukemia.

Optimization of the salvage regimen is required to improve prognosis in primary refractory or relapsed acute myeloid leukemia (AML). In fit patients, a bridge to allogeneic transplant is the primary purpose of salvage. We tested the combination of fractionated gemtuzumab ozogamicin with cytarabine and mitoxantrone (MYLODAM schema) with primary endpoint of efficacy and safety. We also attempted to define predictive factors for survival and response after salvage. We included 58 patients with a median age at salvage of 56 years. The overall response rate was 67%. Leukemia-free survival (LFS) and overall survival (OS) at 2 years was 36% (95% CI: 23-49) and 54% (95% CI: 39-68), respectively. Treatment-related mortality was 7%. Three veno-occlusive diseases (SOS/VOD) occurred during salvage. In the allogeneic group of 28 patients (48%), LFS and OS at 2 years was 57 % (95% CI: 36.3-77.5) and 69 % (95% CI: 49.3-88.7), respectively. Incidences of nonrelapse mortality, grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD were 16%, 40%, and 45%, respectively. A GO-based intensive regimen is a viable option for salvage therapy and a feasible schedule as a bridge to allogeneic transplant.

Thiotepa and antithymocyte globulin-based conditioning prior to haploidentical transplantation with posttransplant cyclophosphamide in high-risk hematological malignancies.

We report results of a thiotepa-based conditioning in haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-CY) and antithymocyte globulin (ATG), for unmanipulated peripheral blood stem cell (PBSC) transplants, in 80 patients with hematological malignancies. Patients in complete remission (CR) received a thiotepa-busulfan-fludarabine (TBF) regimen, while patients with relapsed/refractory (R/R) malignancies received a sequential regimen consisting of thiotepa-etoposide-cyclophosphamide (TEC) and reduced-intensity conditioning (RIC). The median age was 52 (range, 17-72) years, 44% patients had R/R disease at transplant, and the median follow-up was 417 (range, 180-1595) days. The median days to neutrophil engraftment was 17 (range, 12-34). The cumulative incidences (CI) of acute graft-versus-host disease (GVHD) grade III to IV, severe chronic GVHD, nonrelapse mortality (NRM), and relapse were 16%, 16%, 26, and 26%, respectively. The 2-year overall survival (OS) and disease-free survival (DFS) were 53% and 47%, respectively. There were no significant differences between the patients in CR and R/R patients in terms of engraftment, GVHD, NRM, relapse, OS, or DFS. We conclude that thiotepa-based regimen with PT-CY can be modified with PBSC and ATG, still providing low toxicity, protection against GVHD, and low relapse incidence. Particularly encouraging are the results with the modification to sequential regimen in R/R patients.