Prednisone vs high-dose dexamethasone in newly diagnosed adult primary immune thrombocytopenia: a randomized trial.

ABSTRACT: A debate exists regarding which type of corticosteroids (standard-dose prednisone [PDN] or high-dose dexamethasone [HD-DXM]) is the best first-line treatment for adult patients with newly diagnosed untreated primary immune thrombocytopenia (pITP). An ad hoc study compared PDN with HD-DXM in newly diagnosed untreated patients with pITP (aged ≥18 but ≤80 years, platelet count of ≤20 or >20 but <50 × 109/L, and bleeding score of ≥8). Patients were randomised to receive PDN 1 mg/kg per day from days 0 to 28 (Arm A) or HD-DXM 40 mg per day for 4 days, every 14 days, for 3 consecutive courses (Arm B). Fifty-nine of 113 patients (52.2%) were randomized to Arm A and 54 of 113 (47.8%) to Arm B. In evaluable patients, total initial responses (complete response [CR], partial response [PR], minimal response [MR]) were 44 of 56 (78.57%) in Arm A and 46 of 49 (93.88%) in Arm B at days 42 and 46, respectively (P = 0.0284). Total final responses (at day 180 from initial response) were 26 of 43 (60.47%) in Arm A and 23 of 39 (58.97%) in Arm B (P = 0.8907). Total persistent responses (at 12 months from initial response) were 25 of 31 (80.65%) in Arm A and 20 of 36 (55.56%) in Arm B (P = 0.0292). Seven relapses occurred. Median follow-up was 44.4 months. Overall survival was 100% at 48 months, overall disease-free survival was 81.11% at 48 months from day 180. PDN and pulsed HD-DXM were well tolerated; HD-DXM allows effective initial responses but less long lasting than PDN. This trial was registered at www.clinicaltrials.gov as #NCT00657410.

Evaluating the Use of a Robot in a Hematological Intensive Care Unit: A Pilot Study.

The aim of the SYRIACA project was to test the capability of a social robot to perform specific tasks in healthcare settings, reducing infection risks for patients and caregivers. The robot was piloted in an Intensive Hematological Unit, where the patients' and healthcare operators' acceptability of the robot was evaluated. The robot's functions, including logistics, surveillance, entertainment, and remote visits, were well accepted. Patients expressed interest in having multiple interactions with the robot, which testifies to its engaging potential and that it provides useful services. During remote visits, the robot reduced perceived stress among patients, alleviating feelings of isolation. The successful implementation of the robot suggests its potential to enhance safety and well-being in healthcare settings.

DNA methylation of hematopoietic stem/progenitor cells from donor peripheral blood to patient bone marrow: implications for allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (AHSCT) is a life-saving treatment for selected hematological malignancies. So far, it remains unclear whether transplanted hematopoietic stem/progenitor cells (HSPCs) undergo epigenetic changes upon engraftment in recipient bone marrow (BM) after AHSCT and whether these changes might be useful in the transplant diagnostics. The purpose of this study was to characterize the whole genome methylation profile of HSPCs following AHSCT. Moreover, the relationship between the observed methylation signature and patient outcome was analyzed. Mobilized peripheral blood (mPB)-HSPCs from seven donors and BM-HSPCs longitudinally collected from transplanted patients with hematological malignancies up to one year from AHSCT (a total of twenty-eight samples) were analyzed using DNA methylation based-arrays. The obtained data showed that DNA methylation of mPB-HSPCs differs between young and adult donors and changes following HSPC engraftment in the BM of recipient patients. Looking at methylation in promoter regions, at 30 days post-AHSCT, BM-HSPCs showed a higher number of differentially methylated genes (DMGs) compared to those of mPB-HSPCs, with a prevalent hyper-methylation. These changes were maintained during all the analyzed time points, and methylation became like the donors after one year from transplant. Functional analysis of these DMGs showed an enrichment in cell adhesion, differentiation and cytokine (interleukin-2, -5 and -7) production and signaling pathways. Of note, DNA methylation analysis allowed to identify a potential "cancer/graft methylation signature" of transplant failure. It was evident in the latest available post-transplant BM-HSPC sample (at 160 days) and surprisingly already in early phase (at 30 days) in patients whose transplant was doomed to fail. Overall, the analysis of HSPC methylation profile could offer useful prognostic information to potentially assess engraftment success and predict graft failure in AHSCT.

Busulfan or Treosulfan Conditioning Platform for Allogeneic Stem Cell Transplantation in Patients Aged >60 Y With Acute Myeloid Leukemia/Myelodysplastic Syndrome: A Subanalysis of the GITMO AlloEld Study.

The conditioning regimens with different alkylators at different doses can influence the outcome of allogeneic stem cell transplantation (SCT), but conclusive data are missing. Methods: With the aim to analyze real-life allogeneic SCTs performed in Italy between 2006 and 2017 in elderly patients (aged >60 y) with acute myeloid leukemia or myelodysplastic syndrome, we collected 780 first transplants data. For analysis purposes, patients were grouped according to the type of alkylator included in the conditioning (busulfan [BU]-based; n = 618; 79%; treosulfan [TREO]-based; n=162; 21%). Results: No significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival, although in the TREO-based group, we observed a greater proportion of elderly patients (P < 0.001); more active diseases at the time of SCT (P < 0.001); a higher prevalence of patients with either hematopoietic cell transplantation-comorbidity index ≥3 (P < 0.001) or a good Karnofsky performance status (P = 0.025); increased use of peripheral blood stem cells as graft sources (P < 0.001); and greater use of reduced intensity conditioning regimens (P = 0.013) and of haploidentical donors (P < 0.001). Moreover, the 2-y cumulative incidence of relapse with myeloablative doses of BU was significantly lower than that registered with reduced intensity conditioning (21% versus 31%; P = 0.0003). This was not observed in the TREO-based group. Conclusions: Despite a higher number of risk factors in the TREO group, no significant differences were observed in nonrelapse mortality, cumulative incidence of relapse, and overall survival according to the type of alkylator, suggesting that TREO has no advantage over BU in terms of efficacy and toxicity in acute myeloid leukemia and myelodysplastic syndrome.

A real-world analysis of PD1 blockade from the Rete Ematologica Pugliese (REP) in patients with relapse/refractory Hodgkin's lymphoma.

Checkpoint inhibitors have significantly changed the prognosis of patients with relapsing refractory classical Hodgkin's lymphoma (cHL), demonstrating excellent results in heavily pretreated patients. However, there is still limited data on the real-world experience with PD-1 inhibitors in cHL. Within the context of the Apulian hematological network (Rete Ematologica Pugliese, REP), we performed a retrospective, multicenter analysis of 66 patients with relapsing refractory cHL who had received PD-1 inhibitors in the non-trial setting. Forty-three patients (65%) were treated with nivolumab and 23 (35%) with pembrolizumab. Thirty-one (47%) and 8 (12%) patients underwent autologous or allogeneic stem cell transplantation prior to checkpoint inhibitor therapy, respectively. The median number of lines of treatment attempted prior to PD-1 inhibitor therapy was 4 (range, 3 to 7). All patients had received brentuximab vedotin prior to checkpoint inhibitor therapy. The overall response rate to PD-1 inhibitors therapy was 70% (47% complete remission (CR) and 23% partial remission (PR)). Twenty-four immune-related adverse events (19 (80%) grades 1-2; 5 (20%) grades 3-4) were documented (4 gastrointestinal, 4 hepatic, 6 fever, 4 hematological, 3 dermatological, 3 allergic rhinitis). Toxicity resolved in all patients, and there were no deaths attributed to checkpoint inhibitor therapy. After a median follow-up of 26 months (range 3-72 months), 54 patients (82%) are alive, and 12 (18%) died. The cause of death was attributed to disease progression in 9 patients and sepsis in 3 patients. After PD-1 inhibitor therapy, 22 patients (33%) relapsed or progressed. The overall survival and progression-free survival at 5 years were 65% and 54%, respectively. This study confirms the efficacy and tolerability of PD-1 inhibitor therapy in relapsed refractory cHL in a real-world setting, demonstrating similar clinical outcomes and toxicity profiles compared to clinical studies.

Comparison of HLA-mismatched unrelated donor transplantation with post-transplant cyclophosphamide versus HLA-haploidentical transplantation in patients with active acute myeloid leukemia.

HLA-haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) is frequently used as treatment for patients with active acute myeloid leukemia (AML). Here, we investigated whether 9/10 HLA-mismatched unrelated donor transplantation (MMUD-HCT) with post-transplant cyclophosphamide (PTCy) is an adequate alternative. Inclusion criteria in this retrospective registry study consisted of adult patients, first HCT with a Haplo donor or MMUD between 2010 and 2020 using PTCy as graft-versus-host disease (GVHD) prophylaxis, and primary refractory or relapsed disease. MMUD patients were pair-matched 1 to 2 with Haplo-recipients. A total of 73 MMUD patients met the inclusion criteria. Their data were compared to those of 146 Haplo patients in a matched-pair analysis. Median follow-up was 27 months in MMUD patients and 36 months in Haplo recipients. Two-year incidences of relapse and non-relapse mortality (NRM) were 40% and 18% in MMUD patients, respectively, versus 50% (P = 0.23) and 24% (P = 0.18) in Haplo recipients. Two-year leukemia-free survival (LFS) and overall survival (OS) was 42% and 46% in MMUD recipients, respectively, versus 26% (P = 0.1) and 28% (P = 0.061) in Haplo-patients. In conclusions, in AML patients with active disease at transplantation, MMUD-HCT results in at least comparable outcomes to Haplo-HCT when PTCy is applied.

Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol.

IDH1/2 mutations are common in acute myeloid leukemia (AML) and represent a therapeutic target. The GIMEMA AML1516 observational protocol was designed to study the prevalence of IDH1/2 mutations and associations with clinico-biological parameters in a cohort of Italian AML patients. We analyzed a cohort of 284 AML consecutive patients at diagnosis, 139 females and 145 males, of a median age of 65 years (range: 19−86). Of these, 38 (14%) harbored IDH1 and 51 (18%) IDH2 mutations. IDH1/2 mutations were significantly associated with WHO PS >2 (p < 0.001) and non-complex karyotype (p = 0.021) when compared to IDH1/2-WT. Furthermore, patients with IDH1 mutations were more frequently NPM1-mutated (p = 0.007) and had a higher platelet count (p = 0.036). At relapse, IDH1/2 mutations were detected in 6 (25%) patients. As per the outcome, 60.5% of IDH1/2-mutated patients achieved complete remission; overall survival and event-free survival at 2 years were 44.5% and 36.1%, respectively: these rates were similar to IDH1/2-WT. In IDH1/2-mutated patients, high WBC proved to be an independent prognostic factor for survival. In conclusion, the GIMEMA AML1516 confirms that IDH1/2 mutations are frequently detected at diagnosis and underlines the importance of recognizing IDH1/2-mutated cases up-front to offer the most appropriate therapeutic strategy, given the availability of IDH1/2 inhibitors.

Therapeutic Management of Patients with FLT3 + Acute Myeloid Leukemia: Case Reports and Focus on Gilteritinib Monotherapy.

Acute myeloid leukemia is a malignant disorder of the bone marrow, characterized by differentiation, clonal expansion, and uncontrolled proliferation of malignant myeloid progenitor cells and by several molecular and genetic abnormalities. A mutation of FMS-like tyrosine kinase 3 gene can be observed in about one-third of cases of acute myeloid leukemia. Two FLT3 inhibitors are actually approved for FLT3 mutated acute myeloid leukemia: midostaurin, a multikinase first generation inhibitor with lower affinity for FLT3 binding, and gilteritinib fumarate, a potent second-generation inhibitor of both FLT3-ITD and TKD. Gilteritinib is a new effective and well-tolerated drug for patients with relapsing or refractory FLT3-positive acute myeloid leukemia. Thanks to its efficacy, low toxicity, its good manageability (oral formulation), this drug is suitable for all the patients, including elderly frail patient with concomitant therapies or pre-existing or underlying diseases, and can be used also in the outpatient setting, reducing risks and costs related to the hospitalization. We report and discuss seven cases of different patients with FLT3 positive acute myeloid leukemia successfully managed with gilteritinib in the real clinical practice.

Myeloablative conditioning with thiotepa-busulfan-fludarabine does not improve the outcome of patients transplanted with active leukemia: final results of the GITMO prospective trial GANDALF-01.

The outcome of refractory/relapsed (R/R) acute leukemias is still dismal and their treatment represents an unmet clinical need. However, allogeneic transplantation (allo-HSCT) remains the only potentially curative approach in this setting. A prospective study (GANDALF-01, NCT01814488; EUDRACT:2012-004008-37) on transplantation with alternative donors had been run by GITMO using a homogeneous myeloablative conditioning regimen with busulfan, thiotepa and fludarabine while GVHD prophylaxis was stratified by donor type. The study enrolled 101 patients; 90 found an alternative donor and 87 ultimately underwent allo-HSCT. Two-year overall survival of the entire and of the transplant population (primary endpoint) were 19% and 22%, without significant differences according to disease, donor type and disease history (relapsed vs refractory patients). Two-year progression-free survival was 19% and 17% respectively. The cumulative incidences of relapse and non-relapse mortality were 49% and 33% at two years. Acute grade II-IV and chronic GVHD occurred in 23 and 10 patients. Dose intensification with a myeloablative two-alkylating regimen as sole strategy for transplanting R/R acute leukemia does seem neither to improve the outcome nor to control disease relapse. A pre-planned relapse prevention should be included in the transplant strategy in this patient population.

GITMO Registry Study on Allogeneic Transplantation in Patients Aged ≥60 Years from 2000 to 2017: Improvements and Criticisms.

Today, allogeneic stem cell transplantation (allo-SCT) can be offered to patients up to age 70 to 72 years and represents one of the most effective curative treatments for many hematologic malignancies. The primary objective of the study was to collect data from the allo-SCTs performed in Italy between 2000 and 2017 in patients aged ≥60 years to evaluate the changes in safety and efficacy outcomes, as well as their distribution and characteristics over time. The Italian Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO) AlloEld study (ClinicalTrials.gov identifier NCT04469985) is a retrospective analysis of allo-SCTs performed at 30 Italian transplantation centers in older patients (age ≥60 years) between 2000 and 2017 (n = 1996). For the purpose of this analysis, patients were grouped into 3 time periods: time A, 2000 to 2005 (n = 256; 12%); time B, 2006 to 2011 (n = 584; 29%); and time C, 2012 to 2017 (n = 1156; 59%). After a median follow-up of 5.6 years, the 5-year nonrelapse mortality (NRM) remained stable (time A, 32.8%; time B, 36.2%; and time C, 35.0%; P = .5), overall survival improved (time A, 28.4%; time B, 31.8%; and time C, 37.3%; P = .012), and the cumulative incidence of relapse was reduced (time A, 45.3%; time B, 38.2%; time C, 30.0%; P < .0001). The 2-year incidence of extensive chronic graft-versus-host disease was reduced significantly (time A, 17.2%; time B, 15.8%; time C, 12.2%; P = .004). Considering times A and B together (2000 to 2011), the 2-year NRM was positively correlated with the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score; NRM was 25.2% in patients with an HCT-CI score of 0, 33.9% in those with a score of 1 or 2, and 36.1% in those with a score of 3 (P < .001). However, after 2012, the HCT-CI score was not significantly predictive of NRM. This study shows that the transplantation procedure in elderly patients became more effective over time. Relapse incidence remains the major problem, and strategies to prevent it are currently under investigation (eg, post-transplantation maintenance). The selection of patients aged ≥60 could be improved by combining HCT-CI and frailty assessment to better predict NRM.

Letermovir Prophylaxis for Cytomegalovirus Infection in Allogeneic Stem Cell Transplantation: A Real-World Experience.

Despite effective treatments, cytomegalovirus (CMV) continues to have a significant impact on morbidity and mortality in allogeneic stem cell transplant (allo-SCT) recipients. This multicenter, retrospective, cohort study aimed to evaluate the reproducibility of the safety and efficacy of commercially available letermovir for CMV prophylaxis in a real-world setting. Endpoints were rates of clinically significant CMV infection (CSCI), defined as CMV disease or CMV viremia reactivation within day +100-+168. 204 adult CMV-seropositive allo-SCT recipients from 17 Italian centres (median age 52 years) were treated with LET 240 mg/day between day 0 and day +28. Overall, 28.9% of patients underwent a haploidentical, 32.4% a matched related, and 27.5% a matched unrelated donor (MUD) transplant. 65.7% were considered at high risk of CSCI and 65.2% had a CMV seropositive donor. Low to mild severe adverse events were observed in 40.7% of patients during treatment [gastrointestinal toxicity (36.3%) and skin rash (10.3%)]. Cumulative incidence of CSCI at day +100 and day +168 was 5.4% and 18.1%, respectively, whereas the Kaplan-Meier event rate was 5.8% (95% CI: 2.4-9.1) and 23.3% (95% CI: 16.3-29.7), respectively. Overall mortality was 6.4% at day +100 and 7.3% at day +168. This real-world experience confirms the efficacy and safety of CMV.

Second allogeneic transplants for multiple myeloma: a report from the EBMT Chronic Malignancies Working Party.

The EBMT Chronic Malignancies Working Party performed a retrospective analysis of 215 patients who underwent a second allo-HCT for myeloma between 1994 and 2017, 159 for relapse and 56 for graft failure. In the relapse group, overall survival (OS) was 38% (30-46%) at 2 years and 25% (17-32%) at 5 years. Patients who had a HLA-identical sibling (HLAid-Sib) donor for their first and second transplants had superior OS (5 year OS: HLAid-Sib/HLAid-Sib: 35% (24-46%); Others 9% (0-17%), p < 0.001). There was a significantly higher incidence of acute grade II-IV GvHD in those patients who had also developed GvHD following their initial HLA-identical sibling allo-HCT (HLAid-Sib/HLAid-Sib: 50% (33-67%); Other 22% (8-36%), p = 0.03). More as opposed to fewer than 2 years between transplants was associated with superior 5-yr OS (31% (21-40%) vs. 10% (1-20%), P = 0.005). On multivariate analysis, consecutive HLA-identical sibling donor transplants conferred a significant OS advantage (0.4 (0.24-0.67), p < 0.001). In the graft failure group, OS was 41% at 2 years. In summary, a second allo-HCT using a HLA-identical sibling donor, if available, provides the best transplant outcomes for relapsed myeloma in this setting.

End-of-treatment PET/CT predicts PFS and OS in DLBCL after first-line treatment: results from GOYA.

GOYA was a randomized phase 3 study comparing obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) vs standard-of-care rituximab plus CHOP in patients with previously untreated diffuse large B-cell lymphoma (DLBCL). This retrospective analysis of GOYA aimed to assess the association between progression-free survival (PFS) and overall survival (OS) with positron emission tomography (PET)-based complete response (CR) status. Overall, 1418 patients were randomly assigned to receive 8 21-day cycles of obinutuzumab (n = 706) or rituximab (n = 712) plus 6 or 8 cycles of CHOP. Patients received a mandatory fluoro-2-deoxy-d-glucose-PET/computed tomography scan at baseline and end of treatment. After a median follow-up of 29 months, the numbers of independent review committee-assessed PFS and OS events in the entire cohort were 416 (29.3%) and 252 (17.8%), respectively. End-of-treatment PET CR was highly prognostic for PFS and OS according to Lugano 2014 criteria (PFS: hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.19-0.38; P < .0001; OS: HR, 0.12; 95% CI, 0.08-0.17; P < .0001), irrespective of international prognostic index score and cell of origin. In conclusion, the results from this prospectively acquired large cohort corroborated previously published data from smaller sample sizes showing that end-of-treatment PET CR is an independent predictor of PFS and OS and a promising prognostic marker in DLBCL. Long-term survival analysis confirmed the robustness of these data over time. Additional meta-analyses including other prospective studies are necessary to support the substitution of PET CR for PFS as an effective and practical surrogate end point. This trial was registered at www.clinicaltrials.gov as #NCT01287741.

Veno-occlusive Disease in HSCT Patients: Consensus-based Recommendations for Risk Assessment, Diagnosis, and Management by the GITMO Group.

Variation in clinical practice affects veno-occlusive disease management, mainly in patients who undergo allogeneic hematopoietic stem cell transplantation. Disputes about diagnostic criteria, treatment, and prophylaxis, due to the lack of high-quality data, are at the base of this variability. With the aim of limiting inconsistency in clinical care, thus improving both patient outcomes and data collection reliability, the Italian Society of Stem cell transplant (Gruppo Italiano Trapianto Midollo Osseo e Terapia Cellulare) launched a collaborative effort to formulate recommendations based on integration of available evidence and expert's consensus. A systematic method, according to US National Institute of Health guidelines and Italian National System for Guidelines, was used. Twenty-nine recommendations were approved with a strong (20) or weak (9) level of agreement, while 26 were rejected. In particular, the panel pointed out the need to achieve an early diagnosis, encouraging the adoption of European Society for Blood and Marrow Transplantation criteria and the prompt use of ultrasonography. Moreover, our experts strongly recommended in favor of prophylactic use of ursodeoxycholic acid. As soon as a veno-occlusive disease diagnosis is established, treatment with defibrotide should be started for at least 21 days. A number of areas of uncertainty, particularly concerning risk stratification and use of diagnostic tools such as elastography has been identified and discussed.

Impact of donor age and kinship on clinical outcomes after T-cell-replete haploidentical transplantation with PT-Cy.

Donor selection contributes to improve clinical outcomes of T-cell-replete haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-Cy). The impact of donor age and other non-HLA donor characteristics remains a matter of debate. We performed a multicenter retrospective analysis on 990 haplo-SCTs with PT-Cy. By multivariable analysis, after adjusting for donor/recipient kinship, increasing donor age and peripheral blood stem cell graft were associated with a higher risk of grade 2 to 4 acute graft-versus-host-disease (aGVHD), whereas 2-year cumulative incidence of moderate-to-severe chronic GVHD was higher for transplants from female donors into male recipients and after myeloablative conditioning. Increasing donor age was associated with a trend for higher nonrelapse mortality (NRM) (hazard ratio [HR], 1.05; P = .057) but with a significant reduced risk of disease relapse (HR, 0.92; P = .001) and improved progression-free survival (PFS) (HR, 0.97; P = .036). Increasing recipient age was a predictor of worse overall survival (OS). Risk of relapse was higher (HR, 1.39; P < .001) in patients aged ≤40 years receiving a transplant from a parent as compared with a sibling. Moreover, OS and PFS were lower when the donor was the mother rather than the father. Pretransplant active disease status was an invariably independent predictor of worse clinical outcomes, while recipient positive cytomegalovirus serostatus and hematopoietic cell transplant comorbidity index >3 were associated with worse OS and PFS. Our results suggest that younger donors may reduce the incidence of aGVHD and NRM, though at higher risk of relapse. A parent donor, particularly the mother, is not recommended in recipients ≤40 years.

Impact of total body irradiation- vs chemotherapy-based myeloablative conditioning on outcomes of haploidentical hematopoietic cell transplantation for acute myelogenous leukemia.

The optimal myeloablative conditioning (MAC) for patients undergoing haploidentical hematopoietic cell transplantation (haplo-HCT) is unknown. We studied the outcomes of total body irradiation (TBI) vs chemotherapy (CT) based MAC regimens in acute myeloid leukemia (AML) patients. The study included 1008 patients who underwent first haplo-HCT with post-transplant cyclophosphamide, following TBI (N = 89, 9%) or CT (n = 919, 91%) based MAC. Patients in the TBI cohort were younger (median age, 38 vs 47 years, P < .01) and more likely to receive BM graft (57% vs 43%, P = .01). Two-year overall chronic GVHD (cGVHD) incidence was 42% vs 27% (P < .01) and extensive cGVHD incidence was 9% vs 12% (P = .33) in TBI and CT cohorts, respectively. Graft failure was reported in two (2%) TBI- and 65 (7%) CT-MAC recipients (P = .08). Death from veno-occlusive disease was reported in one (3%) TBI and 11 (3%) CT patients who died during the study period. In the multivariate analysis, TBI was associated with increased risk for overall cGVHD (hazard ratio = 1.95, 95% confidence interval:1.2-3.1, P < .01) compared to CT-based MAC. The choice of conditioning regimen did not impact relapse incidence, leukemia-free survival, non-relapse mortality, overall survival or GVHD-relapse-free survival in multivariate analysis. In conclusion, major transplant outcomes were not statistically different between TBI-based MAC and CT-based MAC in patients with AML after haplo-HCT/PTCy.

Effect of the Thiotepa Dose in the TBF Conditioning Regimen in Patients Undergoing Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in Complete Remission: A Report From the EBMT Acute Leukemia Working Party.

BACKGROUND: Allogeneic stem cell transplantation is a potentially curative therapy for patients with acute myeloid leukemia (AML) after achieving complete remission (CR). The aim of this study is to evaluate the optimal dose of thiotepa, administered as part of the thiotepa-busulfan-fludarabine (TBF) conditioning regimen for allogeneic stem cell transplantation in adults with AML in CR. PATIENTS AND METHODS: In a retrospective multicenter analysis, we identified 240 patients allotransplanted from matched related or unrelated donors or T replete haplo-identical donors. We compared the transplantation outcomes of patients who received 5 mg/kg thiotepa and 2 days of intravenous busulfan at 6.4 mg/kg (T1B2F) versus those who received 10 mg/kg thiotepa with 2 days of intravenous busulfan at 6.4 mg/kg (T2B2F). The median follow-up was 20 months. RESULTS: On univariate analysis, the incidence of acute graft versus host disease (GVHD) grade II to IV was significantly lower in the T1B2F group (19%) versus 32% in the T2B2F group (P = .029). This result was confirmed on multivariate analysis; acute GVHD was higher for patients receiving T2B2F (hazard ratio, 2.22; P = .024). No significant change in non-relapse mortality, progression-free survival, or overall survival was observed between the 2 groups. CONCLUSION: T2B2F is associated with a higher incidence of acute GVHD compared with T1B2F. These results suggest that a lower dose-intensity of thiotepa and busulfan in the TBF regimen may yield better results in patients with AML in CR.

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors: A Registry-Based Study of the Italian Blood and Marrow Transplantation Society (GITMO).

We performed a nationwide registry-based analysis to describe the clinical outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who underwent an allogeneic hematopoietic stem cell transplantation (HSCT) after a tyrosine kinase inhibitor (TKI)-based treatment A total of 441 patients were included in the study. The median age at HSCT was 44 years (range, 18 to 70 years). All 441 patients (100%) received TKI before HSCT (performed between 2005 and 2016). Of these 441 patients, 404 (92%) were in cytologic complete remission (CR), whereas the remaining 37 (8%) had active disease at the time of HSCT. Molecular minimal residual disease (MRD) was negative in 147 patients (36%) at the time of HSCT. The donor was unrelated in 46% of patients. The most prevalent source of stem cells was peripheral blood (70%). The conditioning regimen was myeloablative in 82% of cases (total body irradiation-based in 50%) and included antithymocyte globulin in 51% of patients. With a median follow-up after HSCT of 39.4 months (range, 1 to 145 months), the probability of overall survival (OS) at 1, 2, and 5 years was 69.6%, 61.1% and 50.3%, respectively, with a median OS of 62 months. Progression-free survival (PFS) at 1, 2, and 5 years was 60.2%, 52.1% and 43.7%, respectively. OS and PFS were significantly better in patients who were in CR and MRD-negative at the time of HSCT compared with patients who were in CR but MRD-positive (50% OS not reached versus 36 months; P = .015; 50% PFS not reached versus 26 months, P = .003). The subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT had a better outcome (5-year OS, 70%). Conversely, the 37 patients who underwent a HSCT with active Ph+ ALL had a median OS of 7 months and a median PFS of 5 months. The 5-year cumulative incidence of relapse was significantly lower in MRD-negative patients (19.5% versus 35.4%; P = .001). Nonrelapse mortality (NRM) after 1, 2, and 5 years was 19.1% (95% confidence interval [CI], 15.5% to 22.9%), 20.7% (95% CI, 17% to 24.7%), and 24.1% (95% CI, 20% to 28.5%), respectively. NRM was significantly lower with a modified European Society for Blood and Marrow Transplantation (mEBMT) risk score of 0 to 2 compared with ≥3 (15% versus 25%; P = .016). The median OS for Ph+ ALL patients who underwent a TKI-based treatment followed by an allogeneic HSCT, in recent years at the GITMO centers, was 62 months. Evaluation of the mEBMT risk score can be useful to predict NRM. Our data confirm that HSCT is a potentially curative treatment for Ph+ ALL with an excellent outcome for the subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT (5-year OS, 70%).