Myeloablative or reduced-intensity/non-myeloablative hematopoietic cell transplantation for Philadelphia-positive acute lymphoblastic leukemia in adults older than 40 years old - a secondary analysis of a CIBMTR database.

Few studies have addressed the role of reduced-intensity conditioning (RIC) and non-myeloablative (NMA) regimens in older adults with Philadelphia acute lymphoblastic leukemia (Ph + ALL). The objective of this current study was to compare the outcomes of RIC/NMA versus TBI-based myeloablative (MAC) regimens in Ph + ALL patients older than 40 years old who underwent hematopoietic cell transplantation (HCT) in CR1. We used a freely available database from the CIBMTR. Transplants were performed between 2013 and 2017. With a median follow-up of 37.6 months, we have included 629 patients. We used propensity score weighting. Three-year OSs were 64% in the TBI-MAC group and 66% in the RIC/NMA group. OS was not different (HR = 0.92; p = 0.69). Three-year relapse incidences were 21.6% and 27.6% in the TBI-MAC and RIC/NMA groups. RIC/NMA was not associated with an increase in relapse rate (HR 1.02; p = 0.91). Three-year NRMs were 24.3% in the TBI-MAC group and 20.3% in the RIC/NMA group. RIC/NMA was not associated with superior NRM (HR 0.88; p = 0.57). In summary, we have shown that RIC/NMA regimens achieve outcomes comparable to TBI-based MAC in Ph+ ALL older patients in CR1 who may tolerate a TBI-based MAC regimen.

Posttransplant cyclophosphamide beyond haploidentical transplantation.

Posttransplant cyclophosphamide (PTCy) has practically revolutionized haploidentical (Haplo) hematopoietic cell transplantation (HCT). Comparisons between Haplo with PTCy and unrelated donor (URD) with conventional graft-versus-host disease (GVHD) prophylaxis have shown comparable overall survival with lower incidences of GVHD with Haplo/PTCy and led to the following question: is it PTCy so good that can be successfully incorporated into matched related donor (MRD) and URD HCT? In this review, we discuss other ways of doing PTCy, PTCy in peripheral blood haploidentical transplants, PTCy in the context of matched related and matched unrelated donors, PTCy with mismatched unrelated donors, and PTCy following checkpoint inhibitor treatment. PTCy is emerging as a new standard GVHD prophylaxis in haploidentical, HLA-matched, and -mismatched HCT.

Total marrow irradiation in hematopoietic stem cell transplantation for hematologic malignancies.

Total body irradiation (TBI) has been an essential component of the conditioning regimen in hematopoietic cell transplantation for many years. However, higher doses of TBI reduce disease relapse at the expense of more significant toxicities. Therefore, total marrow irradiation and total marrow and lymphoid irradiation have been developed to deliver organ-sparing targeted radiotherapy. Data from different studies show that TMI and TMLI can be safely administered in escalating doses in association with different chemotherapy conditioning regimen protocols, in situations with unmet needs, such as multiple myeloma, high-risk hematologic malignancies, relapsed or refractory leukemias, and elderly or frail patients, with low rates of transplant-related mortality. We reviewed the literature on applying TMI and TMLI techniques in autologous and allogeneic hematopoietic stem cell transplantation in different clinical situations.

Molecular profile of patients with myelofibrosis: a 10-year experience.

OBJECTIVE: To analyze the karyotype test and myeloid panel with next-generation sequencing findings in patients with myelofibrosis, and to compare transplant characteristics in patients referred for bone marrow transplantation. METHODS: Retrospective, single-center study with patients diagnosed with myelofibrosis treated at Hospital Israelita Albert Einstein between 2010 and 2020. RESULTS: A total of 104 patients with myelofibrosis were examined. Patients who had not been submitted to tests in our service were excluded. The final sample comprised 69 patients. Of these 69, 56 were submitted to karyotyping and 22 to myeloid panel with next-generation sequencing. Karyotype was normal in 60% of the patients and altered in 40%. The prevalence of high-risk molecular mutations was higher in patients referred for bone marrow transplantation (100% versus 50%). The median follow-up of transplant patients was 2.4 years and the overall survival at 2 years was 80% (95%CI: 62-100%). CONCLUSION: The molecular analysis enables estimating the patient's risk and thus instituting more aggressive treatment such as bone marrow transplant for patients at higher risk, being a relevant tool to guide therapy. Given the significance of molecular analysis for therapeutic decision-making in myelofibrosis, collection and disclosure of data on the prevalence of cytogenetic changes and findings of next-generation sequencing in affected patients is important.

ATG in HLA-Matched, Peripheral Blood, Hematopoietic Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Secondary Analysis of a CIBMTR Database.

w?>Peripheral blood stem cells (PBSC) are the preferred grafts for hematopoietic cell transplantation (HCT), according to the CIBMTR. Donor recovery is faster with PBSC harvest, but PBSC is associated with higher chronic graft-versus-host disease (GVHD) and poorer quality of life. Anti-T-cell globulin (ATG) is polyclonal IgG from rabbits or horses immunized with human thymocytes or a human T-cell line, which may reduce GVHD in HCT and improve outcomes. The objective of this study was to analyze the impact of ATG in HLA-matched related (MRD) and matched (HLA 8/8) unrelated donor (MUD) HCT. We used a freely available CIBMTR database published online for secondary analyses. The database included patients ≥ 40 years old who have undergone their first PBSC MRD or MUD HCT for acute myeloid leukemia or myelodysplastic syndrome with or without ATG between 2008 and 2017. Patients who received posttransplant cyclophosphamide or alemtuzumab were excluded. Overall survival was not different with ATG (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 1.00-1.19; P = .06) compared with no ATG. Relapse rate was higher with ATG (HR = 1.29; 95% CI, 1.17-1.43; P < .001) and non-relapse mortality was lower with ATG (HR = 0.84; 95% CI, 0.72-0.98; P = .03). Grades II-IV acute GVHD was significantly lower with ATG (HR = 0.77; 95% CI, 0.69-0.87; P < .001) but not grades III-IV acute GVHD (HR = 0.85; 95% CI, 0.69-1.04; P = .11). Both chronic GVHD (HR = 0.54; 95% CI, 0.48-0.60; P < .001) and moderate/severe chronic GVHD (HR = 0.45; 95% CI, 0.38-0.52; P < .001) were lower with ATG. There was an interaction between ATG and conditioning regimen for relapse rate and overall survival. Relapse rate was higher in those who received reduced-intensity (RIC) or non-myeloablative (NMA) conditioning regimens and ATG, compared with MAC ± ATG or RIC without ATG (interaction test, P = .003). Overall survival was also poorer with ATG and RIC or NMA conditioning regimens (interaction test, P = .03). Our results show that ATG can mitigate the more severe forms of chronic GVHD without impairing overall survival in HLA-matched HCT with PBSC grafts and myeloablative conditioning regimen. ATG should be standard in this population. © 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Molecular profile of patients with myelofibrosis: a 10-year experience

ABSTRACT Objective To analyze the karyotype test and myeloid panel with next-generation sequencing findings in patients with myelofibrosis, and to compare transplant characteristics in patients referred for bone marrow transplantation. Methods Retrospective, single-center study with patients diagnosed with myelofibrosis treated at Hospital Israelita Albert Einstein between 2010 and 2020. Results A total of 104 patients with myelofibrosis were examined. Patients who had not been submitted to tests in our service were excluded. The final sample comprised 69 patients. Of these 69, 56 were submitted to karyotyping and 22 to myeloid panel with next-generation sequencing. Karyotype was normal in 60% of the patients and altered in 40%. The prevalence of high-risk molecular mutations was higher in patients referred for bone marrow transplantation (100% versus 50%). The median follow-up of transplant patients was 2.4 years and the overall survival at 2 years was 80% (95%CI: 62-100%). Conclusion The molecular analysis enables estimating the patient's risk and thus instituting more aggressive treatment such as bone marrow transplant for patients at higher risk, being a relevant tool to guide therapy. Given the significance of molecular analysis for therapeutic decision-making in myelofibrosis, collection and disclosure of data on the prevalence of cytogenetic changes and findings of next-generation sequencing in affected patients is important.

Costs of matched-sibling, unrelated, and haploidentical hematopoietic cell transplantation and risk factors for greater financial burden - a Brazilian FACT-accredited single-center analysis.

The complexity and costs of hematopoietic cell transplantation (HCT) have increased over the last decades with the popularization of unrelated donor (URD) transplantation and the introduction of haploidentical transplantation with posttransplant cyclophosphamide. Few studies have addressed this issue. The objective of this study was to analyze HCT costs in a single FACT-accredited private non-profit hospital. We included 79 patients who underwent HCT between 2018 and 2020. We have included all costs from admission day until D + 180. We used a lognormal regression. Median age was 53 y/o and most donors were unrelated (51%). Costs were higher with haploidentical donor (42%, p = 0.017, compared with URD), higher HCT-CI (15% for each point, p = 0.0056), and in patients with liver or gastrointestinal GVHD (45%, p = 0.033), and lower in patients who received CD34 > 2.5 × 10E6/kg (42%, p = 0.0038). We built a score based on the following risk factors: HCT-CI > 3, CD34 ≤ 2.5 × 10E6/kg, haploidentical donor, and donor age > 30 y/o. Patients with 2 + risk factors (N = 53) had a median cost of USD 226,156.00, compared with USD 93,048.00 in patients with zero or 1 point (N = 26, p < 0.0001). In summary, we have shown that HCT costs are higher with lower doses of CD34 cells, haploidentical HCT (provided that the costs of stem cell procurement and ATG are not included), and in patients with higher HCT-CI. Prospective and refined cost analyses comparing haploidentical and URD transplants, as well as effective strategies for patients with higher HCT-CI scores, are warranted. We found no difference in costs between URD and MSD transplantation.

Lower levels of cyclosporine between days 0 and +21 may reduce later relapses without increasing graft-versus-host disease in children and adolescents with acute lymphoblastic leukemia who undergo myeloablative TBI-based allogeneic hematopoietic cell transplantation.

BACKGROUND: The degree of immunosuppression required for adequate graft-versus-host disease (GVHD) prevention, while keeping an adequate graft-versus-leukemia effect, in children with acute leukemia has not been established. We report the results of a retrospective comparison of cyclosporine levels and relapse rate in children and adolescents with acute lymphoblastic leukemia (ALL). METHODS: Patients <21 y/o with ALL in remission who underwent TBI-based hematopoietic cell transplantation from related or unrelated donors between 2008 and 2021 were included. Cyclosporine levels were measured twice a week and we calculated the area under the curve (AUC) from D0 to D + 7, D + 14, and D + 21. RESULTS: We included 76 patients. There was a trend towards a lower incidence of relapse in patients with a mean AUC < 200 ng/ml at D + 21 (HR = 0.41; p = .08). The 5-year relapse rate was 26.9% for patients with a mean AUC < 200 ng/ml at D + 21 and 43.9% for patients with a mean AUC≥200 ng/ml at D + 21. Relapse protection was restricted to relapses happening after D + 120 (HR = 0.21; p = .04). CONCLUSIONS: Our results show evidence that pediatric patients with ALL might benefit from lower cyclosporine levels between D0 and D + 21 without a detectable increase in GVHD. Large prospective studies comparing different cyclosporine levels are awaited.

Risk factors for adverse outcomes following haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide: a two-center analysis.

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for several malignant hematologic diseases and alternative donors, including haploidentical, play a significant role in HCT. Despite the increasing use of haplo-HCT with PTCy, some questions remain open. The objective of the present study was to investigate risk factors for adverse outcomes after haplo-HCT with PTCy. This is a retrospective study conducted at two Brazilian centers. A total of 103 patients with hematologic malignancies who underwent first allogeneic, haploidentical HCT with PTCy were included. Risk factors for death were age at transplant (HR = 1.03 for each year; p = 0.002) and high/very high disease risk index (DRI; HR = 2.77; p = 0.0007) and mother as the donor compared with other donors (HR = 3.53; p = 0.005). In multivariate analysis, PFS was significantly poorer for older patients (HR = 1.02; p = 0.006), high/very high DRI (HR = 2.39; p = 0.003), and mother as the donor compared with other donors (HR = 3.18; p = 0.006). Relapse rate was higher for high/very high DRI (HR = 4.01; p = 0.002) and mother as the donor compared with other donors (HR = 2.52; p = 0.05). NRM was higher for older patients (HR = 1.03 for each year; p = 0.03). Tacrolimus was a protective factor for grades II-IV aGVHD (HR = 0.46; p = 0.04) compared with cyclosporine. Peripheral blood (PBSC) was a risk factor for cGVHD (HR = 3.48; p = 0.006), while tacrolimus was protective (HR = 0.30; p = 0.009). Mother as the donor compared with other donors was also a risk factor for poorer OS, PFS, and relapse, suggesting that this combination should be avoided. Tacrolimus was protective for both grades II-IV aGVHD and cGVHD, suggesting that tacrolimus may be more effective than cyclosporine in preventing GVHD. PBSC was a risk factor for cGVHD without any impact on relapse. Prospective studies comparing tacrolimus with cyclosporine are awaited.

Outcomes after Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide: A Systematic Review and Meta-Analysis Comparing Myeloablative with Reduced-Intensity Conditioning Regimens and Bone Marrow with Peripheral Blood Stem Cell Grafts.

Haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplantation cyclophosphamide (PTCy) may be the sole available curative option for several hematologic malignancies. However, the best choice of conditioning regimen and graft source has not been established. This study was conducted to compare myeloablative conditioning (MAC) regimens with reduced-intensity conditioning (RIC) regimens and peripheral blood stem cell (PBSC) grafts with bone marrow (BM) grafts in the haplo-HCT setting with PTCy. We performed a systematic review and meta-analysis of studies comparing MAC with RIC and PBSC with BM in the haplo-HCT. The search was conducted in PubMed and TRIALS on February 2, 2021, without a date limit. We excluded studies with >30% non-PTCy graft-versus-host disease (GVHD) prophylaxis and >30% nonmalignant diseases. We screened 570 abstracts from PubMed and TRIALS and selected 20 for full-text review and 17 for inclusion in the qualitative and quantitative analyses. For PBSC versus BM grafts, we found no difference in overall survival (OS; hazard ratio [HR], 1.05; P = .61; nPBSC = 1983; nBM = 2124), progression-free survival (PFS; HR, 0.95; P = .52; nPBSC = 2663, nBM = 2769), graft-versus-host disease (GVHD)-free relapse-free survival (GRFS; HR, 1.16; P = .07; nPBSC = 1454; pBM = 1647), or nonrelapse mortality (HR, 1.14; P = .13; nPBSC = 1664; nBM = 1862). Relapse was lower with the use of PBSC grafts (HR, 0.84; P = .001; nPBSC = 2663; nBM = 2769). The rates of acute GVHD (aGVHD) and chronic GVHD (cGVHD) were higher with PBSC grafts (aGVHD grade II-IV: HR, 1.67; P < .001; nPBSC = 2663; nBM = 2802; aGVHD grade III-IV: HR, 1.82; P < .001; nPBSC = 1826; nBM = 2000; cGVHD: HR, 1.46; P = .002; nPBSC = 2686; nBM = 2815). Engraftment was higher with PBSC grafts (HR, 1.27; P < .001; nPBSC = 1461; nBM = 1717). Comparing MAC and RIC, the use of MAC was associated with less relapse (HR, 0.70; P < .001; nMAC = 1929; nRIC = 2662), higher nonrelapse mortality (HR, 1.24; P = .002; nMAC = 2016; nRIC = 2790), but better PFS (HR, 0.86; P = .002; nMAC = 1929; nRIC = 2662). There were no differences between the 2 conditioning regimens in OS (HR, .95; P = .32; nMAC = 2123; nRIC = 3155), GRFS (HR, 0.97; P = .67; nMAC = 1182; nRIC = 1330), grade II-IV aGVHD (HR, 1.01; P = .81; nMAC = 2099; nRIC = 3090), or cGVHD (HR, 1.05; P = .44; nMAC=1929; nRIC = 2662). This analysis shows that the use of BM grafts is associated with comparable outcomes as seen with PBSC grafts despite a lower incidence of GVHD and a higher relapse rate. The use of MAC regimens is associated with improved PFS. These results suggest that for fit patients, MAC remains the optimal conditioning regimen in terms of mortality, and that the use of PBSC grafts may further decrease relapse risk and hasten engraftment, provided that further strategies can be incorporated to decrease GVHD. Prospective comparisons are awaited.

Treatment of relapsed/refractory multiple myeloma in the bortezomib and lenalidomide era: a systematic review and network meta-analysis.

Multiple myeloma (MM) is an incurable disease, and patients usually receive multiple lines of therapy. Due to the abundance of novel treatments for MM, we conducted a network meta-analysis to identify combinations that could fare better than others in relapsed/refractory MM, in the setting of novel drugs. We searched PubMed and Cochrane databases for phase III trials in previously treated MM that had lenalidomide or bortezomib in the control arm. The primary endpoint was progression-free survival (PFS), extracted as hazard-ratio. We used the P score to rank treatments. Thirteen studies were included. All but two studies compared one novel agent against two, with or without dexamethasone. Based on the P score, daratumumab and pegylated liposomal doxorubicin had a higher probability of achieving better PFS, followed by isatuximab, carfilzomib, pomalidomide, and panobinostat. Although most overall survival data were not mature enough, the addition of a second or third novel agent to either immunomodulatory (IMID) or proteasome inhibitor (PI) backbone seemed to improve survival (HR = 0.84, 95CI 0.77-0.92). Severe adverse events were more frequent with isatuximab, panobinostat, and pomalidomide. In summary, in the absence of trials directly comparing two novel agents-based therapies, we provide a tool that indirectly compares these newer therapies and that can help physicians to prioritize some regimens over others.

Impact of CD34 Cell Dose and Conditioning Regimen on Outcomes after Haploidentical Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Relapsed/Refractory Severe Aplastic Anemia.

Severe aplastic anemia (SAA) is a life-threatening disease that can be cured with allogeneic cell transplantation (HCT). Haploidentical donor transplantation with post-transplantation cyclophosphamide (haplo-PTCy) is an option for patients lacking an HLA-matched donor. We analyzed 87 patients who underwent haplo-PTCy between 2010 and 2019. The median patient age was 14 years (range, 1 to 69 years), most were heavily transfused, and all received previous immunosuppression (25% without antithymocyte globulin). Almost two-thirds (63%) received standard fludarabine (Flu)/cyclophosphamide (Cy) 29/total body irradiation (TBI) 200 cGy conditioning, and the remaining patients received an augmented conditioning: Flu/Cy29/TBI 300-400 (16%), Flu/Cy50/TBI 200 (10%), or Flu/Cy50/TBI 400 (10%). All patients received PTCy-based graft-versus-host disease (GVHD) prophylaxis. Most grafts (93%) were bone marrow (BM). The median duration of follow-up was 2 years and 2 months. The median time to neutrophil recovery was 17 days. Primary graft failure occurred in 15% of the patients, and secondary or poor graft function occurred in 5%. The incidences of grade II-IV acute GVHD was 14%, and that of chronic GVHD was 9%. Two-year overall survival and event-free survival (EFS) were 79% and 70%, respectively. EFS was higher for patients who received augmented Flu/Cy/TBI (hazard ratio [HR], .28; P = .02), and those who received higher BM CD34 cell doses (>3.2 × 10E6/kg) (HR, .29; P = .004). The presence of donor-specific antibodies before HSCT was associated with lower EFS (HR, 3.92; P = .01). Graft failure (HR, 7.20; P < .0001) was associated with an elevated risk of death. Cytomegalovirus reactivation was frequent (62%). Haploidentical HCT for SAA is a feasible procedure; outcomes are improved with augmented conditioning regimens and BM grafts with higher CD34 cell doses.

Impact of Anti-CMV IgG Titers and CD34 Count Prior to Hematopoietic Stem Cell Transplantation from Alternative Donors on CMV reactivation.

Cytomegalovirus (CMV) reactivation remains one of the main infectious complications following hematopoietic stem cell transplantation (HSCT). In this study, we explored the role of anti-CMV antibody titers in HSCT from alternative donors and to compare the risk of CMV reactivation between posttransplant cyclophosphamide-based haploidentical HSCT and antithymocyte globulin-based unrelated donor (URD) HSCT. We included 98 CMV-positive patients, 30 undergoing haploidentical HSCT and 68 undergoing URD HSCT. The majority of patients had a malignant disease (84%), received a myeloablative conditioning regimen (78%), and received a bone marrow graft (90%). The median pretransplantation anti-CMV IgG level was 109 U/mL. With median follow-up of 2.2 years, a total of 72 CMV reactivations occurred in 50 patients. There was no difference in CMV reactivation pattern between haploidentical HSCT recipients and URD HSCT recipients. In multivariable analysis until the first event, the incidence of CMV reactivation was higher in patients with anti-CMV IgG levels >100 U/mL (hazard ratio [HR], 2.38; P = .005) and in patients diagnosed with grade II-IV acute graft-versus-host disease (GVHD) (HR, 10.8; P = .003) after day +50 and lower in patients who received higher doses of CD34 cells (HR, .44; P = .006). In multivariable analysis for recurring events, the incidence of CMV reactivation was higher in patients receiving reduced-intensity conditioning (HR, 1.69: P = .04) and in patients with acute GVHD (HR, 1.88; P = .02), and lower in those who received higher doses of CD34 cells (HR, .55; P = .01). In summary, we have shown that pretransplantation anti-CMV IgG titers are correlated with CMV reactivation risk. More studies are needed to assess how this information can be incorporated in HSCT. The use of high-dose cellular grafts, a modifiable risk factor, also protects against CMV reactivation.

Hematopoietic cell transplantation in pediatric patients with acute leukemias or myelodysplastic syndrome using unrelated adult or umbilical cord blood donors in Brazil.

The choice of alternative donors for HCT for patients without an HLA-matched related donor depends on several factors. We compared major HCT outcomes in 212 consecutive children transplanted at 11 centers in Brazil for acute leukemia or MDS from an HLA-matched unrelated donor (MUD, n = 95), mismatched unrelated donor (MMUD, n = 47) or unrelated umbilical cord blood (UCB, n = 70). Most had ALL (61%), bone marrow (57%) as the graft source and 95% received a MAC regimen. The 3-year OS probability were 57, 55, and 37% after HCT from MUD, MMUD, and UCB, respectively (HR 1.68, 95%CI 1.07-2.63; P = .02). In comparison with MUD, OS was similar after transplantation of a ≥ 6/8 HLA-matched or a high cell dose (>5 × 107 TNC/kg) CB unit (HR 1.41, 95%CI 0.88-2.27; P = .15). NRM was higher for UCB (HR 3.90, 95%CI 1.43-10.7; P = .01) but not for MMUD (HR 1.03, 95%CI 0.53-2.00; P > .20). Advanced disease (HR 2.05, 95%CI 1.26-3.33; P < .001) and UCB with high probability of being < 6/8 HLA-matched (HR 5.34, 95%CI 2.0-13.9; P < .001) were associated with higher mortality. Relapse and acute GVHD were similar among groups, while PGF was higher among UCB transplants (P = .002) and chronic GVHD among MMUD group (HR 2.88, 95% CI 1.05-7.88; P = .04). Our results suggest that in Brazil HCT outcomes performed with MMUD and MUD donors were comparable, while with UCB units < 6/8 HLA-matched were associated with higher NRM for children with acute leukemia or MDS.

Outcomes after Haploidentical Stem Cell Transplantation with Post-Transplantation Cyclophosphamide in Patients with Primary Immunodeficiency Diseases.

Allogeneic hematopoietic stem cell transplantation (HCT) can cure primary immunodeficiency diseases (PID). When a HLA-matched donor is not available, a haploidentical family donor may be considered. The use of T cell-replete haploidentical HCT with post-transplantation cyclophosphamide (haplo-PTCy) in children with PID has been reported in few case series. A donor is usually readily available, and haplo-PTCy can be used in urgent cases. We studied the outcomes of 73 patients with PID who underwent haplo-PTCy, including 55 patients who did so as a first transplantation and 18 who did so as a salvage transplantation after graft failure of previous HCT. The median patient age was 1.6 years. Most of the children were male (n = 54) and had active infection at the time of transplantation (n = 50); 10 children had severe organ damage. The diagnosis was severe combined immunodeficiency (SCID) in 34 patients and non-SCID in 39 (Wiskott-Aldrich syndrome; n = 14; chronic granulomatous disease, n = 10; other PID, n = 15). The median duration of follow-up of survivors was 2 years. The cumulative incidence of neutrophil recovery was 88% in the SCID group and 84% in non-SCID group and was 81% for first transplantations and 83% after a salvage graft. At 100 days, the cumulative incidence of acute GVHD grade II-IV and III-IV was 33% and 14%, respectively. The majority of patients reached 200/µL CD4+ and 1000/µL CD3+ cell counts between 3 and 6 months. The estimated 2-year overall survival was 66%; it was 64% for SCID patients and 65% for non-SCID patients and 63% for first HCT and 77% for salvage transplantations. Twenty-five patients died, most of them due to infection early after transplantation (before 100 days). In conclusion, haplo-PTCy is a feasible procedure, can cure two-thirds of children with PID, and can be used as rescue treatment for previous graft failure. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

A Case Series of Post-Transplantation Cyclophosphamide in Unrelated Donor Hematopoietic Cell Transplantation for Aplastic Anemia.

Patients with severe aplastic anemia (SAA) who fail immunosuppressive therapy have a dismal prognosis. Hematopoietic stem cell transplantation (HSCT) from an unrelated donor (URD) is one of the most effective treatment options. Two institutions have independently adopted a post-transplantation cyclophosphamide (PTCy) approach for patients with SAA undergoing HSCT from a URD. Thirteen patients were included, 11 of whom had been treated with immunosuppressive therapy. Eight patients had a mismatched URD. All patients were conditioned with fludarabine, cyclophosphamide, and total body irradiation, in various dosage combinations. PTCy was given at a dose of 100 mg/kg. Two patients died, and overall survival was 85% at 2 years. All patients engrafted, but 1 patient developed secondary graft failure. Of the 11 patients alive after 2 years, 9 had complete donor chimerism. All surviving patients were transfusion-independent. Ten patients (77%) had cytomegalovirus reactivation, and 2 patients had more than 1 reactivation. No Epstein-Barr virus reactivation or post-transplantation lymphoproliferative disease was observed. Four patients had mild hemorrhagic cystitis. In summary, our findings show that PTCy is a promising treatment for patients with SAA undergoing URD HSCT.

Haploidentical Transplantation with Post-Transplant Cyclophosphamide versus Unrelated Donor Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

Hematopoietic stem cell transplantation (HSCT) is the standard treatment for patients with high-risk hematologic malignancies. Only approximately 25% of siblings are HLA-matched, and thus alternative donors-unrelated or haploidentical-are usually the only options available. This meta-analysis aimed to compare haploidentical HSCT with post-transplantation cyclophosphamide and unrelated donor (URD) HSCT. We searched the PubMed and Cochrane databases for pertinent studies indexed between 2008 and 2018. Twenty observational studies (with a total of 1783 haploidentical HSCT recipients and 6077 URD HSCT recipients) were included. Results for overall survival, graft-versus-host disease (GVHD), nonrelapse mortality (NRM), and relapse incidence were pooled. Measures of association used were hazard ratios and risk differences. The median age was 51 years for haploidentical transplant recipients and 52 years for URD transplant recipients. Peripheral blood stem cell (PBSC) grafts were more frequent in the URD transplant recipients (85%) than in the haploidentical transplant recipients (31%). Overall survival was not different between the 2 groups. NRM was lower for haploidentical transplantation. All forms of GVHD (acute grades II-IV and III-IV and moderate, severe, and extensive chronic) were lower with haploidentical donor HSCT. The risk of chronic GVHD was fairly proportional to the differential use of PBSC grafts across studies, however. All included studies were retrospective, representing the major limitation of this meta-analysis. In conclusion, haploidentical HSCT for hematologic malignancies achieved the same overall survival as URD HSCT, with a lower incidence of GVHD and NRM. The increased frequency of PBSC use in the unrelated donor group could partially explain the higher cGVHD rate. Haploidentical transplantation with post-transplantation cyclophosphamide should strongly be considered as the first option for adult patients with hematologic malignancies who do not have matched sibling donors in experienced centers. This systematic review has been registered at PROSPERO (65790).