Haploidentical Transplant with Post-Transplant Cyclophosphamide for Acute Myeloid Leukaemia and Myelodysplastic Syndromes Patients: The Role of Previous Lines of Therapy.

Background: Allogeneic haematopoietic stem-cell transplant is an option, potentially curative, for high-risk acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients. Post-transplant cyclophosphamide administration allows for the selection of haploidentical donors in patients who are eligible for the procedure but do not have a fully matched donor since it can overcome the HLA barrier. There is still an active debate on whether intensifying the conditioning regimen is necessary with haploidentical donors when peripheral blood stem cells are used as the graft source. Herein, we report our decennial experience of haploidentical stem-cell transplant using peripheral blood stem cells (haplo-PBSC) at King's College Hospital. Objectives: The primary objective was to evaluate overall survival (OS) following haplo-PBSC. Secondary objectives were total OS for patients with less than two previous lines of therapy, OS according to cytomegalovirus (CMV) reactivation, incidence of transplant-related mortality (TRM), graft-versus-host disease (GVHD) and GVHD-relapse-free survival (GRFS). Results: One-year and three-year total OS were 62% and 43%, respectively, with a median OS of 22 months. One-year and three-year OS for patients with ≤2 and those with >2 previous lines of therapy were 72% and 55%, and 60% and 22%, respectively (p-value=0.04). The median OS in patients with >2 previous and ≤2 lines of therapy was 16 and 49 months, respectively. Cumulative incidence (CI) of relapse was 25% with a median time to relapse of 5 months (range 1 - 38 months). Conclusions: Haploidentical haematopoietic stem-cell transplant is potentially curative in chemosensitive AML and MDS and offers a high rate of prolonged remission. Our cohort further confirms the role of consolidative haploidentical transplant in patients in complete remission and highlights that patients with heavily pre-treated disease may not benefit from this strategy.

Relapse and transformation to myelodysplastic syndrome and acute myeloid leukemia following immunosuppressive therapy for aplastic anemia is more common as compared to allogeneic stem cell transplantation with a negative impact on survival.

We studied the incidence of relapse, transformation to myelodysplastic syndrome/acute myeloid leukemia, and survival in patients with aplastic anemia (AA) surviving more than 1 year after ATG/ALG-based immunosuppressive therapy (IST) between 1985 and 2020. Four-hundred seventy patients (413 adults and 57 children) were studied, and data were compared with 223 patients who underwent matched sibling donor transplant (MSD HSCT). Median follow-up is 50 months (12-359). Relapse occurred in 21.9% at a median time of 33.5 months (5-228) post IST. Twenty-six (5.5%) patients progressed to PNH, while 20 (4.3%) evolved to MDS/AML. Ten-year estimated overall survival (OS) is 80.9 ± 3% and was significantly better in patients without an event (85.1 ± 4%) compared to relapse (74.6% ± 6.2%) or clonal evolution (12.8% ± 11.8%) (p = 0.024). While the severity of AA (p = 0.011) and type of ATG (p = 0.028) used predicted relapse, only age at IST administration influenced clonal evolution (p = 0.018). Among HSCT recipients, relapse rates were 4.9% with no clonal evolution, and the 10-year OS was 94.5 ± 2%. In patients who survived 1 year following IST, outcomes were good except with clonal evolution to MDS/AML. These outcomes, however, were still inferior compared to matched sibling donor HSCT.

Haploidentical Natural Killer Cell Therapy as an Adjunct to Stem Cell Transplantation for Treatment of Refractory Acute Myeloid Leukemia.

Refractory acute myeloid leukemia (AML), defined as failure of two cycles of induction therapy at diagnosis or of one cycle at relapse, represents a subgroup with poor outcomes. Haploidentical natural killer cell (NK) therapy is a strategy that is being explored in refractory malignancies. Historically, at our center, patients with refractory AML have been treated with cytoreductive therapy (fludarabine + cytosine + granulocyte colony-stimulating factor ± idarubicin or mitoxantrone + etoposide) followed by 1-week rest and then reduced-intensity transplant with fludarabine + melphalan. We used the same backbone for this trial (CTRI/2019/02/017505) with the addition of CD56-positive cells from a family donor infused 1 day after the completion of chemotherapy. CD56-positive selection was done using a CliniMACS Prodigy system (Miltenyi Biotec, Bergisch Gladbach, Germany) followed by overnight incubation in autologous plasma with 2 micromolar arsenic trioxide and 500 U/mL of interleukin-2. From February 2019, 14 patients with a median age of 29 years (interquartile range [IQR]: 16.5-38.5) were enrolled in this trial. Six were females. Six had primary refractory AML while eight had relapsed refractory AML. The median CD56-cell dose infused was 46.16 × 106/kg (IQR: 25.06-70.36). One patient withdrew consent after NK cell infusion. Of the 13 patients who proceeded to transplant, five died of immediate post-transplant complications while two did not engraft but were in morphologic leukemia-free state (both subsequently died of infective complications after the second transplant). Of the remaining six patients who engrafted and survived beyond 1 month of the transplant, two developed disease relapse and died. The remaining four patients are alive and relapse free at the last follow-up (mean follow-up duration of surviving patients is 24 months). The 2-year estimated overall survival for the cohort was 28.6% ± 12.1% while the treatment-related mortality (TRM) with this approach was 38.5% ± 13.5%. Haploidentical NK cell therapy as an adjunct to transplant is safe and needs further exploration in patients with AML. For refractory AML, post-transplant NK infusion and strategies to reduce TRM while using pre-transplant NK infusion merit exploration.

Clinical significance of end of induction measurable residual disease monitoring in B-cell acute lymphoblastic leukemia: A single center experience.

The assessment of measurable residual disease (MRD) has emerged as a powerful prognostic tool for both pediatric and adult acute lymphoblastic leukemia (ALL). This retrospective study aimed to evaluate the prognostic relevance of the end of induction MRD in B-cell acute lymphoblastic leukemia (B ALL) patients. The study included 481 patients who underwent treatment for B ALL between August 2012 and March 2019 and had their MRD at the end of induction assessed by flow cytometry. Baseline demographic characteristics were collected from the patient's clinical records. Event free survival (EFS) and relapse free survival (RFS) were calculated using Kaplan-Meier analysis and survival estimates were compared using the log-rank test. End of induction MRD and baseline karyotype were the strongest predictors of EFS and RFS on multivariate analysis. The EFS was inversely related to the MRD value and the outcomes were similar in patients without morphological remission at the end of induction and patients in remission with MRD ≥1.0%. Even within the subgroups of ALL based on age, karyotype, BCR::ABL1 translocation and the treatment protocol, end of induction MRD positive patients had poor outcomes compared to patients who were MRD negative. The study outcome would help draft end of induction MRD-based treatment guidelines for the management of B ALL patients.

Fludarabine-Based Low-Intensity Conditioning for Fanconi Anemia is Associated with Good Outcomes in Aplastic Anemia but not in MDS - a Single-Center Experience.

Background: Hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with Fanconi Anemia (FA) with hematological abnormalities. Materials and Methods: This is a retrospective analysis of patients with FA who underwent a matched-related donor HSCT. Results: Sixty patients underwent 65 transplants between 1999-2021 using a fludarabine-based low-intensity conditioning regimen. The median age at transplant was 11 years (range: 3-37). Aplastic anemia (AA) was the underlying diagnosis in 55 (84.6%), while 8 (12.4%) had myelodysplastic syndrome (MDS) and 2 (3%) had acute myeloid leukemia (AML). The conditioning regimen used was Fludarabine with low-dose Cyclophosphamide for aplastic anemia and Fludarabine with low-dose Busulfan for MDS/AML. Graft versus host disease (GVHD) prophylaxis consisted of Cyclosporine and methotrexate. Peripheral blood was the predominant stem cell graft source (86.2%). Engraftment occurred in all but one patient. The median time to neutrophil and platelet engraftment was 13 days (range: 9-29) & 13 days (range: 5-31), respectively. Day 28 chimerism analysis showed complete chimerism in 75.4 % and mixed chimerism in 18.5%. Secondary graft failure was encountered in 7.7%. Grade II-IV acute GVHD occurred in 29.2%, while Grade III-IV acute GVHD occurred in 9.2%. Chronic GVHD was seen in 58.5% and was limited in most patients. The median follow-up is 55 months (range: 2-144) & the 5-year estimated overall survival (OS) is 80.2 ± 5.1%. Secondary malignancies were noted in 4 patients. The 5-year OS was significantly higher in patients undergoing HSCT for AA (86.6 + 4.7%) as compared to MDS/AML (45.7+16.6%) (p= 0.001). Conclusion: SCT using a fully matched donor provides good outcomes with low-intensity conditioning regimens in patients with FA who have aplastic marrow.

Profile and Predictors of Infection Following Anti-thymocyte Globulin or Anti-lymphocyte Globulin with Cyclosporine in Aplastic Anemia.

Immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG) and Cyclosporine (CSA) in aplastic anaemia (AA) results in improvement of blood counts between 3 and 6 months for the majority of patients. Infection is the most lethal complication in aplastic anemia and may arise due to several factors. We performed this study to determine the prevalence and predictors of specific infection types before and after IST. Six hundred and seventy-seven (546 adults; 434 males) transplant ineligible patients received ATG and CSA between 1995 and 2017. All patients who were transplant ineligible and received IST in this period were included. Infections before IST was seen in 209 (30.9%) and in 430 (63.5%) patients post IST. There were 700 infective episodes in the six months post-IST, including 216 bacterial, 78 fungal, 33 viral, and 373 culture-negative febrile episodes. Infections were highest (98, 77.8%) in very severe aplastic anaemia as compared to Severe AA (SAA) and Non-Severe AA (NSAA) (p < 0.001). Infections were also significantly higher in those who did not respond to ATG (71.1% vs. 56.8%, p = 0.003). At six months post-IST were 545 (80.5%) alive, and there were 54 (7.9%) deaths due to infection. Significant predictors of mortality were paediatric AA, very severe aplastic anaemia, pre or post ATG infections, and lack of response to ATG. Mortality was highest in those with combined bacterial and fungal infections post IST (p < 0.001). We conclude that infections are a common complication (63.5%) of IST. Mortality was highest when both bacterial and fungal infections were present. Routine use of growth factors and prophylactic antifungal and antibacterial agents was not part of our protocol, despite which 80.5% of the cohort was alive at the end of six months.

Total marrow lymphoid irradiation and cyclophosphamide is associated with low toxicity and good outcomes in patients undergoing hematopoietic stem cell transplantation for acute lymphoblastic leukemia and chronic myeloid leukemia in lymphoid blast crises - A phase I study.

INTRODUCTION: Total marrow lymphoid irradiation (TMLI) can deliver higher doses of irradiation without increasing toxicity compared to Total body irradiation (TBI). METHODS: Twenty adult patients undergoing hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia with lymphoid blast crises (CML-LBC) received TMLI and cyclophosphamide for conditioning. Ten patients each received 13.5 or 15 Gy of TMLI. The graft source was peripheral blood stem cells in all, and donors included matched related (n = 15), haplo-identical (n = 3) or matched unrelated donors (n = 2). RESULTS: The median cell dose infused was 9 × 106 CD34/kg (range 4.8-12.4). Engraftment occurred in all (100%) at a median of 15 days (range: 14-17). Toxicity was low with hemorrhagic cystitis seen in two but no sinusoidal obstruction syndrome. Acute GVHD occurred in 40% while chronic GVHD was seen in 70.5%. Viral infections were seen in 55% while blood stream bacterial infections occurred in 20% and invasive fungal disease (IFD) in 10%. The Day 100 non-relapse mortality (NRM) was 10%. At a median follow up of 25 months (range 2-48), two patients have relapsed. Overall survival at 2 years is 80% while the disease-free survival is 75%. CONCLUSIONS: The combination of TMLI and cyclophosphamide for myeloablative conditioning is associated with low toxicity and favorable early outcomes in patients undergoing HSCT for ALL and CML-LBC.

Decentralized manufacturing of anti CD19 CAR-T cells using CliniMACS Prodigy®: real-world experience and cost analysis in India.

Chimeric Antigen Receptor (CAR) T cell therapy is an accepted standard of care for relapsed/refractory B cell malignancies. However, the high cost of existing industry-driven centralized production makes this therapy unaffordable in low and middle-income countries. Decentralized or point of care manufacturing has the potential to overcome some of these challenges. Here we demonstrate a decentralized manufacturing process for anti-CD19-CAR-T cells using a fully automated closed system (Miltenyi CliniMACS Prodigy®) is feasible in a developing country setting. Validation run data, as part of a pre-clinical trial safety evaluation, demonstrates the successful and robust manufacturing of anti-CD19 CAR-T cells with T cell expansion of 25 to 47-fold. The median transduction efficiency was 48.8%, with a median viability of 98% and fulfillment of all standard release criteria assays for clinical application. Evaluation of production costs in an academic, not for profit setting in India provide a benchmark for low and middle-income pricing which could greatly increase access to this therapy. Based on our analysis, the cost per product would be approximately $35,107 US dollars. Our data highlights the safety, efficacy, and reproducibility of the process for use in planned future clinical trials.

Haemodynamic stroke in a rare adult presentation of osteopetrosis.

Osteopetrosis refers to a collection of metabolic bone diseases with impaired osteoclastic activity resulting in abnormally dense and dysplastic bone. Cranial involvement results in severe complications, including compressive nerve palsies, hydrocephalus and tonsillar herniation. Ischaemic stroke is very rarely reported in osteopetrosis, resulting from vascular impingement. We report a young adult woman with CLCN7 (Chloride Voltage-Gated Channel 7) gene-related osteopetrosis and ischaemic stroke resulting from diffuse and focal arterial stenosis and severe myelophthisic anaemia. Acute management included blood transfusions, lay-flat positioning and fever treatment, which resulted in partial recovery of her initial neurological deficits. Our case highlights this very rare stroke syndrome's unique mechanisms and treatment challenges.

Molecular characterization of triple-negative myeloproliferative neoplasms by next-generation sequencing.

The role of next-generation sequencing (NGS) in identifying mutations in the driver, epigenetic regulator, RNA splicing, and signaling pathway genes in myeloproliferative neoplasms (MPNs) has contributed substantially to our understanding of the disease pathogenesis as well as disease evolution. NGS aids in determining the clonal nature of the disease in a subset of these disorders where mutations in the driver genes are not detected. There is a paucity of real-world data on the utility of this test in the characterization of triple-negative myeloproliferative neoplasms (TN-MPN). In this study, 46 samples of TN-MPN (essential thrombocythemia (ET) = 17; primary myelofibrosis (PMF) = 23; & myeloproliferative neoplasm unclassified (MPN-u) = 6) were screened for markers of clonality using targeted NGS. Among these, 25 (54.3%) patients had mutations that would help determine the clonal nature of the disease. Eight of the 17 TN-ET (47%) and 13 of the 23 TN-PMF (56.5%) patients had noncanonical mutations in the driver genes and mutations in the genes involved in epigenetic regulation. Identification of mutations categorized as high molecular markers (HMR) in 2 patients helped classify them as PMF with high risk according to the MIPSS 70 scoring system. A novel mutation in the MPIG6B (C6orf25) gene associated with childhood myelofibrosis was detected in a 14-year-old girl. The presence of clonal hematopoiesis could be confirmed in four of the six MPN-u patients in this cohort. This study demonstrates the utility of NGS in improving the characterization of TN-MPN by establishing clonality and detecting noncanonical mutations in driver genes, thereby aiding in clinical decision-making.

Single Dose of Ivermectin is not Useful in Patients with Hematological Disorders and COVID-19 Illness: A Phase II B Open Labelled Randomized Controlled Trial.

Repurposed drugs may reduce morbidity and mortality in patients with hematological disorders who develop COVID-19 illness. 112 patients with predominantly hematological illnesses were randomized to receive standard of care, ivermectin 12 mg [Iv 12] or 24 mg [Iv24] for asymptomatic, mild, or moderate COVID 19 illness. Serial respiratory samples for rRT-PCR samples were sent on Day 3, 5 and 7. rRT-PCR negativity and ≥ 2 log10 reduction in viral loads on day 3, 5 and 7 were similar between the 3 treatment groups across all disease categories. Symptom progression occurred in 26 patients [21.6%] with no difference across 3 treatment groups. Twenty-two patients [18.3%] have expired while 98 [81.7%] survived. Survival rates were similar across treatment groups [controls-80.5%, Iv12-77.5%, Iv24-87.2% respectively]. Overall, poorer survival was seen with moderate illness compared to others [51.6% vs 92.1%; p = 0.000] and was the only significant risk factor identified on multivariate analysis. In this Phase II randomised trial, single dose of 12 or 24 mg of ivermectin did not reduce viral loads, prevent symptom progression, or reduce mortality in patients with predominantly haematological illnesses who develop mild to moderate COVID 19 illness.

Endothelial Activation and Stress Index-Measured Pretransplantation Predicts Transplantation-Related Mortality in Patients with Thalassemia Major Undergoing Transplantation with Thiotepa, Treosulfan, and Fludarabine Conditioning.

The use of thiotepa-treosulfan-fludarabine conditioning regimen and peripheral blood stem cell grafts is associated with improved outcomes of hematopoietic stem cell transplantation (HCT) in patients with high-risk thalassemia major. However, there remains a need to identify predictors of poor outcomes in this cohort to further optimize outcomes. The Endothelial Activation and Stress Index (EASIX) is a biomarker shown to predict survival in various settings, including graft-versus-host disease, veno-occlusive disease, and nonrelapse mortality following allogeneic HCT. In this retrospective analysis, we evaluated the role of EASIX-PreTx (measured before conditioning therapy) as a biomarker in predicting day +100 transplantation-related mortality (TRM+100) in 281 patients with thalassemia major who underwent HCT with a uniform conditioning regimen using thiotepa-treosulfan-fludarabine at our center between January 2012 and December 2019. The median patient age was 9 years (range, 1 to 25 years), and 109 (38.8%) were females. According to the Pesaro classification (with Vellore modification), 3 patients (1.1%) were class I, 34 (12.1%) were class II, 134 (47.7%) were class III low risk, and 110 (39.1%) were class III high risk. Stem cell donors were matched sibling (n = 218; 77.6%), matched related nonsibling (n = 23; 8.2%), or matched unrelated (n = 40; 14.2%). Five patients (1.8%) received a bone marrow graft, and the others received a peripheral blood stem cell graft. Thirty-eight patients (13.5%) had TRM+100. EASIX-PreTx was available for 184 patients (65.5%). The median EASIX-PreTx was significantly higher in patients with TRM+100 compared with those without TRM+100 (1.09 versus .75; P = .008). An EASIX-PreTx cutoff of .85 had 70.4% sensitivity and 62% specificity for predicting TRM+100. The TRM+100 for patients with EASIX-PreTx >.85 was significantly higher than those with EASIX <.85 (24.4% versus 7.5%; P = .003). In a uniform subgroup of class III patients undergoing allogeneic HCT (n = 156), EASIX-PreTx was an independent predictor of TRM+100.

Disease Status at Transplant has a Significant Impact on Outcomes of Autologous Transplantation (ASCT) in Patients with Hodgkin Lymphoma-A Single Center Experience.

High dose chemotherapy followed by autologous stem cell transplantation is the treatment of choice for relapsed Hodgkin lymphoma (HL). We analyzed 100 consecutive patients who underwent ASCT at our center between January 1999 and June 2019 for relapsed or refractory disease with a median age of 28 years (range: 9-65). At ASCT, 59 were in complete remission (CR) while 31 achieved partial remission (PR) and 10 had refractory disease (RD). Most had BEAM conditioning with a median infused cell dose of 4.84 × 106 CD 34 cells/kg. Prompt engraftment occurred in 97 patients at a median of 11 days. The day 100 transplant related mortality (TRM) was 5%. At a median of 37 months follow up, 79 patients are alive while 34 have relapsed. The 3-year event free survival (EFS) and overall survival (OS) are 62.3 ± 0.5% and 77.9 ± 4.4% respectively. The 3-year OS for patients in CR, PR and RD were 83.0 ± 5.2%, 78.4 ± 8.1% and 38.9 ± 1.7 respectively [p = 0.007] while the 3-year EFS for CR, PR and RD were 73.1 ± 6.2%, 61.3 ± 9.2% and 25.0 ± 1.5 respectively [p = 0.005]. Only disease status at time of ASCT was found to correlate with both OS and EFS. ASCT for HL is associated with good outcomes and low TRM. Disease status at ASCT impacted both OS and EFS and strategies to improve outcomes in patients with refractory disease needs to be explored.

BK Polyomavirus Hemorrhagic Cystitis in Hematopoietic Cell Transplant Recipients.

Introduction: BK polyomavirus-associated hemorrhagic cystitis (BKPyV-HC) is a well-recognized infective complication of hematopoietic cell transplant (HCT) with increased organ dysfunction and mortality. This study was performed to describe the local incidence, risk factors, and outcomes of BKPyV infection. Methods: This retrospective case-control study was conducted between 2007 and 2016 from a tertiary hospital in South India. We identified HCT recipients diagnosed with BKPyV-HC and compared them with recipients over the same period who did not develop BK virus infection matched for age, sex, diagnosis, and donor type. We collected data from central electronic medical records and databases maintained in the departments of hematology and virology. Results: Over the study period, 1276 transplants were performed, of which 262 patients (20.5%) developed HC and 105 (8.2%) were BKPyV-positive. Grade 3 HC was most commonly (57.1%) seen, and the median time to develop BKPyV-HC was 35 (range 0-858) days. Survival was significantly lower in the cases (42.9% vs. 61%, P < 0.05). On univariate analysis, the protective effect of nonmyeloablative conditioning (P = 0.04), residual disease at the time of transplant in malignant conditions (P = 0.001), lower CD34 dose (P = 0.006), presence of acute graft versus host disease (GVHD, P < 0.001), reactivation of cytomegalovirus infection (P < 0.001), and presence of bacterial urinary tract infection (UTI) (P < 0.001) were significant factors. Multivariate logistic regression confirmed the presence of acute GVHD (P = 0.041), bacterial UTI (P < 0.001), and residual disease (P = 0.009) at HCT as significant risk factors for BKPyV-HC. Conclusions: Our study affirms the homogeneity of BKPyV-HC disease in low- and middle-income HCT settings with prior reports and the need for therapeutic strategies to reduce its resultant mortality.

Mutation Profile in BCR-ABL1-Negative Myeloproliferative Neoplasms: A Single-Center Experience From India.

OBJECTIVE/BACKGROUND: Recurrent somatic mutations in the JAK2, calreticulin (CALR), and the MPL genes are described as drivers of BCR-ABL1-negative myeloproliferative neoplasms (MPN) that includes polycythemia vera (PV), essential thrombocytosis (ET), primary myelofibrosis (PMF), and MPN unclassified (MPN-U). METHODS: We describe the mutation profile and clinical features of MPN cases diagnosed at a tertiary care center. JAK2V617F and MPL (S505/W515) mutations were screened by allele-specific polymerase chain reaction, while CALR exon 9 and JAK2 exon 12 mutations were screened by fragment analysis/Sanger sequencing. Among the 1,570 patients tested for these mutations during the study period, 407 were classified as MPN with a diagnosis of PV, ET, PMF, and MPN-U seen in 30%, 17%, 36%, and 17%, respectively, screened. RESULTS: Similar to previous reports from Asian countries, the incidence of PMF was the highest among the classic MPN. JAK2V617F mutation was detected in 90% of PV, 38% of ET, 48% of PMF, and 65% of MPN-U. JAK2 exon 12 mutations were seen in 5.7% of PV and 1.4% of PMF. CALR exon 9 mutations were seen in 33% of ET, 33% of PMF, and 12% of MPN-U. MPL mutations were detected in 2.8%, 2.7%, and 2.9% of ET, PMF, and MPN-U, respectively. Fifteen % of PMF, 26% of ET, and 22% of MPN-U were triple negative. CONCLUSION: There was a significantly higher incidence of CALR mutation in PMF and ET cases. Our study highlights the challenges in the diagnosis of JAK2-negative PV and the need for harmonization of criteria for the same.

Haploidentical transplantation is feasible and associated with reasonable outcomes despite major infective complications-A single center experience from India.

Haploidentical stem cell transplantation (SCT) using post-transplantation cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis is a reasonable therapeutic option for patients who do not have a matched sibling donor. Between 2010 and June 2020, 257 patients underwent 269 Haploidentical transplantations, including 122 children. Indications included both malignant (56.8%) and non-malignant (43.2%) diseases. Conditioning regimens included both myeloablative (57.6%) and nonmyeloablative regimens (42.4%). Peripheral blood stem cells were the predominant graft source (96.2%). Based on the disease risk index, patients were classified into early-, intermediate-, and late-stage disease. Engraftment was seen in 205 patients (76.2%) whereas 39 (14.4%) died before engraftment and 23 (8.6%) had primary graft failure. The cumulative incidence of grade II-IV acute GVHD was 47.8% with a 23.9% incidence of grade III-IV acute GVHD. Chronic GVHD was seen in 41.9% with a 15.4% incidence of extensive chronic GVHD. More than 90% had at least 1 documented infection with a 44% incidence of bacterial, 71% viral, and 38% fungal infection. The 2-year overall survival is 40.5% ± 3.2% with a higher survival among children (48.2% ± 3.4%) compared to adults (34.2% ± 4.1%). Survival was poor with late-stage disease (23.6% ± 4.3%) compared to early- (62.5% ± 7.5%) and intermediate-stage (50.3% ± 4.3%). Factors adversely affecting survival included older age of patient (P = .007), late disease status (P = .000), nonmyeloablative conditioning regimen (P = .003), bone marrow as graft source (P = .006), presence of acute GVHD (P = .069), primary graft failure (P = .000), and presence of a documented bacterial (P = .000) and fungal infection (P = .000). On multivariate analysis, older age (P = .027), presence of acute GVHD (P = .033), documented bacterial infection (P = .000), documented fungal infection (P = .000) and primary graft failure (P = .012) continued to remain significant. Haploidentical SCT offers a reasonable chance of cure for patients with both malignant and nonmalignant hematological diseases. Strategies to reduce aGVHD and infection related mortality needs to be explored further. © 20XX American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Hematopoietic Stem Cell Transplantation is a cost-effective alternative to enzyme replacement therapy in Gaucher Disease.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a feasible treatment option for Gaucher disease (GD). Among 60 patients diagnosed with GD over 15 years (2004-2019), three children who underwent HSCT (January-November 2017) were analyzed. Two boys (cases 1 and 2) and one girl (case 3) received HSCT at 3, 7, and 10 years of age, respectively. Cases 1 and 3 received haplo-HSCT, while case 2 received HLA-identical related-donor transplantation. The CD 34 cell dose was 5-10×106/kg. Neutrophil and platelet engraftment were between days +14 to +21 and days +15 to +76. Post-HSCT chimerism was a 100% donor. None of the patients developed acute or significant chronic graft versus host disease (GVHD). All patients had febrile episodes with negative blood cultures. Major post-HSCT complications included EBV-viremia and recurrent lobar pneumonia in case 1, delayed engraftment and pure red cell aplasia (PRCA) in case 2, and pericardial effusion with tamponade in case 3. At a median of 49 months post-HSCT, all patients were stable with improved growth, absent organomegaly, and had completed immunization. The median cost of treatment was $23,038.96, which is 10.7%-13% of the yearly enzyme replacement therapy (ERT) cost. In a resource-limited setting like India, ERT is a financial burden and not a sustainable option. With improved treatment outcomes, haplo-HSCT is now a possible option for almost every patient, even if no HLA-identical donor is identified.