Dr. Sandeep Soni specializes in stem cell transplant and gene therapy for children with non-malignant disorders e.g , life-threatening genetic disorders, aplastic anemia and hemoglobinopathies,specifically transfusion dependent Thalassemia and severe symptomatic Sickle Cell Disease (SCD). Dr. Soni did his hematopoietic stem cell transplantation (HSCT) training at Hadassah Medical Center in Jerusalem, Israel and at MD Anderson Cancer Center in Houston, TX. He has been treating patients with cellular therapies for over 15 years. The focus of his clinical research is to develop reduced intensity conditioning (RIC) regimens to alleviate the short-term and long-term toxicities associated with HSCT, and to bring innovative gene-therapy treatments to the clinic to treat hemoglobinopathies and other rare genetic disorders. The goal of gene therapy treatments is to correct or edit the defective genes in patients’ own stem cells (autologous) and infuse them back to the patient after adequate conditioning, thereby obviating the need to perform HSCT. Dr. Soni has also worked at bluebird bio, Inc. and Crispr Therapeutics, Inc. to develop their gene therapy programs. He is currently the PI of multiple gene therapy studies being conducted at LPCH, He specializes in translational research, clinical trial design and stem cell manipulations.
Cellular Therapy, Gene Therapy, Stem Cell Transplant
Sickle Cell Disease, Thalassemia
Reduced Intensity Conditioning
- Gene Therapy for rare pediatric disorders
- Stem Cell Transplant and Gene Therapy
- Thalassemia, Sickle Cell Disease, Reduced Intensity Conditioning
Clinical Associate Professor, Pediatrics - Stem Cell Transplantation
Honors & Awards
ASBMT Tandem Meetings Best Abstract Award for Clinical Research, ASBMT/CIBMTR (Feb 2015)
Boards, Advisory Committees, Professional Organizations
Cell Therapy Liaison to FDA, ASBMT (2017 - Present)
Organizing Committee, ISCT (2018 - 2019)
Organizing Committee, ISCT (2019 - Present)
Board Certification: Hematology/Oncology, American Board of Pediatrics (2004)
Fellowship:UT MD Anderson Cancer Center (2003) TX
Residency:Childrens Hospital at Montefiore Pediatric Residency (2002) NY
Medical Education:Maulana Azad Medical College (1988) India
Internship:Maulana Azad Medical College (1987) India
Current Research and Scholarly Interests
Translational Medicine, Cellular/Gene Therapy Clinical Trials, Phase I studies
- Chemistry, manufacturing and controls for gene modified hematopoietic stem cells CYTOTHERAPY 2019; 21 (3): 358–66
A Phase 2 Trial of KIR Mismatched Unrelated Donor Transplantation Using In Vivo T-cell Depletion with ATG in AML: Children's Oncology Group AAML05P1 Study.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
AML patients receiving killer immunoglobulin-like receptor (KIR) mismatched haploidentical HSCT have improved survival. COG AAML05P1 is a prospective phase 2 trial of unrelated donor (URD) HSCT in which KIR typing of donors was available to the treating physician at donor selection, aiming to determine feasibility (defined as the ability to obtain donor samples from unrelated donors and perform and return KIR data before transplant) of prospective selection of KIR mismatched donors and effect on outcomes. The study accrued 90 evaluable patients. Patients ≤ 30 years old with high risk AML at presentation or relapsed AML were eligible. After enrollment as many as 5 potential URD samples were KIR typed (including gene expression) in a central laboratory and results reported to the treating physician, who made the final donor selection. Cases were categorized as KIR matched or mismatched using different published strategies. Overall survival, disease-free survival (DFS), and relapse did not differ significantly by KIR mismatch. Acute GVHD was significantly lower in recipients of KIR mismatched stem cells (35% vs 60%, p= 0.027). We examined DFS according to time to NK-receptor recovery after HSCT. NKp44 recovery was significantly associated with KIR mismatch and with decreased DFS and increased relapse risk in multivariate Cox analysis (p= 0.006 and 0.009, respectively). We show that prospective selection of URD according to KIR type was feasible, acute GVHD was reduced, but survival did not differ using any model of KIR mismatch. The study enrolled mostly matched transplants, however, so ligand-ligand mismatch was rare and therefore sample size was insufficient to determine potential benefit according to this model. Cord blood recipients demonstrated a trend towards improved DFS with KIR mismatch, but the study was not powered to detect a difference in this small subset of patients. Our data suggest that recovery of NK receptor expression might influence DFS after HSCT.
View details for DOI 10.1016/j.bbmt.2019.12.723
View details for PubMedID 31870931
Unrelated Donor Transplantation in Children with Thalassemia using Reduced-Intensity Conditioning: The URTH Trial
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
2018; 24 (6): 1216–22
Allogeneic hematopoietic stem cell transplantation (HSCT) can cure transfusion-dependent thalassemia (TDT). In a multicenter trial we investigated the efficacy of reduced-intensity conditioning (RIC) before unrelated donor (URD) HSCT in children with TDT. Thirty-three children, ages 1 to 17 years, received bone marrow (BM) or umbilical cord blood (UCB) allografts. Median time to neutrophil engraftment was 13 days (range, 10 to 25) and 24 days (range, 18 to 49) and platelet engraftment 23 days (range, 12 to 46) and 50 days (range, 31 to 234) after BM and UCB allografts, respectively. With a median follow-up of 58 months (range, 7 to 79), overall and thalassemia-free survival was 82% (95% CI, .64% to .92%) and 79% (95% CI, .6% to .9%), respectively. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) after BM and UCB allografts was 24% and 44%; the 2-year cumulative incidence of chronic extensive GVHD was 29% and 21%, respectively; 71% of BM and 91% of UCB recipients discontinued systemic immunosuppression by 2 years. Six patients who had Pesaro risk class 2 (n = 5) and class 3 (n = 1) died of GVHD (n = 3), viral pneumonitis (n = 2) and pulmonary hemorrhage (n = 1). Outcomes after this RIC compared favorably with URD HSCT outcomes for TDT and supported engraftment in 32 of 33 patients. Efforts to reduce GVHD and infectious complications are being pursued further.
View details for PubMedID 29374585
View details for PubMedCentralID PMC5993578
Gene Therapy in Patients with Transfusion-Dependent beta-Thalassemia
NEW ENGLAND JOURNAL OF MEDICINE
2018; 378 (16): 1479–93
Donor availability and transplantation-related risks limit the broad use of allogeneic hematopoietic-cell transplantation in patients with transfusion-dependent β-thalassemia. After previously establishing that lentiviral transfer of a marked β-globin (βA-T87Q) gene could substitute for long-term red-cell transfusions in a patient with β-thalassemia, we wanted to evaluate the safety and efficacy of such gene therapy in patients with transfusion-dependent β-thalassemia.In two phase 1-2 studies, we obtained mobilized autologous CD34+ cells from 22 patients (12 to 35 years of age) with transfusion-dependent β-thalassemia and transduced the cells ex vivo with LentiGlobin BB305 vector, which encodes adult hemoglobin (HbA) with a T87Q amino acid substitution (HbAT87Q). The cells were then reinfused after the patients had undergone myeloablative busulfan conditioning. We subsequently monitored adverse events, vector integration, and levels of replication-competent lentivirus. Efficacy assessments included levels of total hemoglobin and HbAT87Q, transfusion requirements, and average vector copy number.At a median of 26 months (range, 15 to 42) after infusion of the gene-modified cells, all but 1 of the 13 patients who had a non-β0/β0 genotype had stopped receiving red-cell transfusions; the levels of HbAT87Q ranged from 3.4 to 10.0 g per deciliter, and the levels of total hemoglobin ranged from 8.2 to 13.7 g per deciliter. Correction of biologic markers of dyserythropoiesis was achieved in evaluated patients with hemoglobin levels near normal ranges. In 9 patients with a β0/β0 genotype or two copies of the IVS1-110 mutation, the median annualized transfusion volume was decreased by 73%, and red-cell transfusions were discontinued in 3 patients. Treatment-related adverse events were typical of those associated with autologous stem-cell transplantation. No clonal dominance related to vector integration was observed.Gene therapy with autologous CD34+ cells transduced with the BB305 vector reduced or eliminated the need for long-term red-cell transfusions in 22 patients with severe β-thalassemia without serious adverse events related to the drug product. (Funded by Bluebird Bio and others; HGB-204 and HGB-205 ClinicalTrials.gov numbers, NCT01745120 and NCT02151526 .).
View details for DOI 10.1056/NEJMoa1705342
View details for Web of Science ID 000430312500004
View details for PubMedID 29669226
Outcomes of Unrelated Donor Stem Cell Transplantion with Post-Transplant Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Patients with Severe Sickle Cell Disease
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
2018; 24 (2): 413–17
Unrelated donor (URD) hematopoietic cell transplantation (HCT) in children with sickle cell disease (SCD) is associated with a high incidence of rejection and graft-versus-host disease (GVHD). We report on the first 4 patients with severe SCD who underwent URD HCT using a novel myeloablative and immunosuppressive regimen composed of busulfan, fludarabine, and antithymocyte globulin with a single dose of post-transplant cyclophosphamide along with tacrolimus and mycophenolate mofetil for GVHD prophylaxis. Three patients engrafted and remain disease-free after a median follow-up period of 2.5 years. One patient had primary graft failure attributed to low stem cell content of the graft. Of interest, none of the engrafted patients developed acute or chronic GVHD. This preparative regimen along with the use of post-transplant cyclophosphamide offers a promising approach for unrelated donor transplants in patients with SCD and needs further corroboration in larger number of patients.
View details for PubMedID 29061531
Veno-occlusive disease after high-dose busulfan-melphalan in neuroblastoma.
Bone marrow transplantation
Survival for high-risk neuroblastoma patients is still suboptimal. Although stem cell transplantation (SCT) is used, there is no consensus as to which conditioning regimen has the greatest efficacy and fewest toxicities. We assessed the incidence of and risk for hepatic veno-occlusive disease (VOD) for neuroblastoma patients who underwent autologous SCT with busulfan and melphalan (BuMel) at eight centers following Children's Oncology Group (COG)-based induction chemotherapy. Data regarding the patients, SCT characteristics, busulfan steady-state concentrations, incidence of VOD, and survival were evaluated. VOD was defined using the modified Seattle criteria. Possible factors associated with VOD (age, busulfan-pharmacokinetic parameters, history of hepatic dysfunction, and day of neutrophil engraftment) were evaluated. Seventy five patients were included and 23 children (31%) developed VOD at a median of 19 days after SCT (range 14-27 days). VOD was the cause of death in 4 patients (5%). In a multivariable analysis, young age (OR 1.7 (95% CI: 1.16-2.56; p = 0.012)) and early day of neutrophil engraftment (OR 1.4 (95% CI: 1.08-2.14; p = 0.041) were associated with the development of VOD. Initial or cumulative busulfan steady-state concentration were not associated with VOD. We found that despite the use of intravenous busulfan with adjusted serum levels, the incidence of VOD remains high in pediatric neuroblastoma patients.
View details for PubMedID 30181580
Phase I Study of Clofarabine and 2-Gy Total Body Irradiation as a Nonmyeloablative Preparative Regimen for Hematopoietic Stem Cell Transplantation in Pediatric Patients with Hematologic Malignancies: A Therapeutic Advances in Childhood Leukemia Consortium Study.
Biology of blood and marrow transplantation
Clofarabine is a purine nucleoside analog with immunosuppressive and antileukemic activity and its inclusion in reduced-intensity regimens could potentially improve outcomes. We performed a prospective phase I study of clofarabine combined with 2 Gy total body irradiation (TBI) as a nonmyeloablative preparative regimen for allogeneic stem cell transplantation in pediatric patients who were considered at high risk of mortality from standard myeloablative regimens. The main goal of the study was to delineate the maximum feasible dose (MFD) of clofarabine in combination with 2 Gy TBI. Eighteen patients, 1 to 21 years of age and in complete remission, were enrolled in 2 strata (matched related donor and unrelated donor) and evaluated for day100 dose-limiting events (DLE) (nonengraftment, nonrelapse mortality [NRM], and severe renal insufficiency) after receiving clofarabine at the starting dose level of 40 mg/m(2). All 6 patients (3 in each stratum) engrafted with no day 100 DLE seen in the first cohort. The dose was increased to 52 mg/m(2) in the next and an expanded cohort (total of 12 patients) and no DLE were observed at day 100 and at the 1-year study endpoint. The regimen was well tolerated with transient transaminitis and gastrointestinal and skin reactions as the common reversible toxicities observed with clofarabine. The dose of 52 mg/m(2) of clofarabine was deemed the MFD. Disease relapse led to mortality in 6 (33%) patients during follow-up with 1-year event-free survival and overall survival of 60% (95% confidence interval [CI], 34 to 79) and 71% (95% CI, 44 to 87), respectively. This regimen leads to successful engraftment using both related and unrelated donors with exceptionally low rates of NRM.
View details for DOI 10.1016/j.bbmt.2017.03.037
View details for PubMedID 28396162
Gene Therapy in a Patient with Sickle Cell Disease.
The New England journal of medicine
2017; 376 (9): 848–55
Sickle cell disease results from a homozygous missense mutation in the β-globin gene that causes polymerization of hemoglobin S. Gene therapy for patients with this disorder is complicated by the complex cellular abnormalities and challenges in achieving effective, persistent inhibition of polymerization of hemoglobin S. We describe our first patient treated with lentiviral vector-mediated addition of an antisickling β-globin gene into autologous hematopoietic stem cells. Adverse events were consistent with busulfan conditioning. Fifteen months after treatment, the level of therapeutic antisickling β-globin remained high (approximately 50% of β-like-globin chains) without recurrence of sickle crises and with correction of the biologic hallmarks of the disease. (Funded by Bluebird Bio and others; HGB-205 ClinicalTrials.gov number, NCT02151526 .).
View details for DOI 10.1056/NEJMoa1609677
View details for PubMedID 28249145
Combined Umbilical Cord Blood and Bone Marrow from HLA-Identical Sibling Donors for Hematopoietic Stem Cell Transplantation in Children With Hemoglobinopathies
PEDIATRIC BLOOD & CANCER
2014; 61 (9): 1690-1694
It is well established that umbilical cord blood and bone marrow are biologically different stem cell sources.We analyzed the feasibility and outcome of hematopoietic stem cell transplantation (HSCT) in 13 children (median age 5.9 years) with hemoglobinopathies after the co- infusion of cord blood (CB) and bone marrow (BM) from the same human leucocyte antigen (HLA) identical sibling donor. We also compared outcomes of children with co-transplantation to outcomes in children with hemoglobinopathies who had received a BM (n = 21) or CB (n = 22) transplant alone.Compared to CB transplant (CBT) recipients, the co-transplant group had more rapid neutrophil (17 vs. 25 days, P = 0.013) and platelet (29 vs. 48 days, P = 0.009) recovery and less transplant related mortality. Patients who received a co-transplant had a lower incidence of ≥ grade II acute (0% vs. 26.3%) and chronic (0% vs. 21%) graft versus host disease (GVHD) compared to BM transplant (BMT) recipients (P = 0.055 and 0.045, respectively). With a median follow-up of >60 months in each treatment group, the 5-year probability of event free survival (EFS) was 100% in the co-transplant group, 90% after BMT and 86% after CBT (P = 0.42).Co-transplantation of CB and BM from HLA-identical sibling donors appears to be a feasible and effective strategy to further optimize outcomes of HSCT for hemoglobinopathies.
View details for DOI 10.1002/pbc.25085
View details for Web of Science ID 000340540600026
View details for PubMedID 24803091
Outcomes of Matched Sibling Donor Hematopoietic Stem Cell Transplantation for Severe Sickle Cell Disease with Myeloablative Conditioning and Intermediate-Dose of Rabbit Anti-Thymocyte Globulin
PEDIATRIC BLOOD & CANCER
2014; 61 (9): 1685-1689
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for sickle cell disease (SCD) in children. Despite excellent outcomes of matched sibling donor (MSD) HSCT, there is still 5-10% chance of rejection and transplant related mortality (TRM) with 12-23% incidence of graft versus host disease (GVHD). We postulated that an intermediate dose of rabbit anti-thymocyte globulin (r-ATG, 10 mg/kg cumulative) would be effective in preventing both rejection and GVHD.Fifteen patients, median age 5 (range 1.5-18) years, underwent MSD HSCT using busulfan (≥ 12.8 mg/kg with first dose pharmacokinetics), cyclophosphamide (total 200 mg/kg) and r-ATG. Bone marrow was the stem cell source; tacrolimus and methotrexate were given for GVHD prophylaxis.All patients achieved donor engraftment and there was no TRM. One patient rejected donor cells at 2 months post-transplant. Majority of the patients had high and sustained level of donor chimerism. None of the patients developed ≥ Grade II GVHD. Incidence of CMV (10%) and EBV (9%) reactivations was low with rapid immune-reconstitution. Overall survival was 100% with event free survival of 93%.Eliminating the risks of TRM and GVHD by optimizing the regimen may lead to further acceptance of HSCT for SCD.
View details for DOI 10.1002/pbc.25059
View details for Web of Science ID 000340540600025
View details for PubMedID 24740582
Successful unrelated umbilical cord blood transplantation for class 3 beta-thalassemia major using a reduced-toxicity regimen
2014; 18 (2): E41-E43
Unrelated umbilical CB transplant for class 3 β-thalassemia major is associated with an increased risk of mortality and non-engraftment. We describe two patients who underwent successful unrelated umbilical CB transplant using a novel reduced-toxicity preparative regimen. This regimen may be sufficiently immunosuppressive and myeloablative to ensure engraftment with reduced risks of toxicity and mortality. Close monitoring of HHV-6 viral load is advised for patients undergoing transplant with this regimen.
View details for DOI 10.1111/petr.12201
View details for Web of Science ID 000330740100001
View details for PubMedID 24330091
Busulfan and melphalan as consolidation therapy with autologous peripheral blood stem cell transplantation following Children's Oncology Group (COG) induction platform for high-risk neuroblastoma: Early results from a single institution
2014; 18 (2): 217-220
Bu-Mel as preparative therapy prior to autologous stem cell rescue was recently shown to be superior to the conventional CEM regimen for HR NBL in Europe. There are no data available on the feasibility and toxicity of Bu-Mel as consolidation therapy following the COG-type induction regimens used in North America. We report early complications and outcomes of patients with HR NBL who received Bu-Mel for consolidation following COG-based induction. Retrospective analysis of all patients who had received Bu-Mel as preparative regimen prior to stem cell rescue for HR NBL was carried out. Toxicity, outcomes, and any delays to receiving radiation or anti-GD2 antibody therapy were analyzed. Six patients undergoing PBSCT had received Bu-Mel. The treatment was well tolerated. Mucositis was the main toxicity; three patients had developed neutropenia fever and none developed pulmonary toxicity. One patient had developed moderate SOS that responded to conservative management. All patients were able to receive and tolerate post-transplant local radiotherapy and ch.14.18 anti-GD2 antibody therapy without any delays. All patients are alive with no disease recurrence. The Bu-Mel regimen is well tolerated and is feasible post-COG-type induction platform.
View details for DOI 10.1111/petr.12202
View details for Web of Science ID 000330740100021
View details for PubMedID 24341617
Outcome of children who experience disease relapse following allogeneic hematopoietic SCT for hematologic malignancies
BONE MARROW TRANSPLANTATION
2013; 48 (5): 661-665
Relapse after allogeneic hematopoietic SCT (HSCT) carries a poor prognosis and is a common cause of death. Outcomes of children who relapse post HSCT are not well known. In this retrospective multicenter study we included 532 patients who underwent allogeneic HSCT and examined the outcomes of 160 patients (30%) who relapsed. Treatment options after relapse included (i) palliative therapy with non-curative intent (n=43), (ii) salvage chemotherapy (without a second HSCT, n=55) or (iii) salvage chemotherapy followed by a second HSCT (n=62). Sixty two patients underwent a second HSCT. The 1-year disease-free survival (DFS) for those given palliative therapy, chemotherapy alone and who underwent a second transplant was <1%, 9% and 50% (P=<0.0001), respectively. The DFS at 1 and 2 year was 50% and 35%, respectively, among the patients who received a second transplant versus 9% and 2% in those who did not (P=<0.0001). In multivariable analysis longer time to relapse (P=0.04) and undergoing a second HSCT (P<0.001) were associated with improved outcome. Withdrawal of immunosuppressive therapy, followed by curative intent chemotherapy should be offered to all patients who relapse after an allogeneic HSCT. A second HSCT should be considered, especially in patients who respond to salvage chemotherapy.
View details for DOI 10.1038/bmt.2012.209
View details for Web of Science ID 000318699800007
View details for PubMedID 23128573
Twice daily i.v. bolus tacrolimus infusion for GVHD prophylaxis in children undergoing stem cell transplantation
BONE MARROW TRANSPLANTATION
2012; 47 (11): 1415-1418
Tacrolimus is routinely administered for GVHD prophylaxis as a 24-h continuous infusion that requires a dedicated i.v. line and thus becomes logistically difficult to administer, especially in young pediatric patients. We investigated the safety and efficacy of twice daily bolus infusions of i.v. tacrolimus in 33 children undergoing hematopoietic stem cell transplantation (HSCT) at our institution. Tacrolimus was started at an initial dose of 0.015 mg/kg i.v. bolus administered as a 2-h infusion and then given at every 12 h to maintain a trough drug level between 5-15 ng/mL. Patients also received short-course MTX (66%) or mycophenolate mofetil (34%) in combination with tacrolimus. No acute infusional toxicities were observed with bolus infusions of i.v. tacrolimus. Nephrotoxicity occurred in 14/33 (42%) patients and 48% developed hypertension (HT). Almost all (94%) patients required magnesium supplements to maintain magnesium (Mg) levels 1.5 mg/dL. In all, 3 (9%) patients developed severe sinusoidal obstruction syndrome (SOS). One patient developed posterior reversible leuko-encephalopathy syndrome (PRES) and one additional patient had tremors. The prevelance of these side-effects was similar to those reported for continuous i.v. administration. In all, 28% of the evaluable patients developed acute GVHDgrade II, though the incidence of severe (grade III-IV) GVHD was only 7%. These results suggest that intermittent bolus i.v. tacrolimus administration is a safe and effective method of GVHD prophylaxis in children.
View details for DOI 10.1038/bmt.2012.59
View details for Web of Science ID 000310795500006
View details for PubMedID 22484323
Advancement of Pediatric Blood and Marrow Transplantation Research in North America: Priorities of the Pediatric Blood and Marrow Transplant Consortium
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
2010; 16 (9): 1212-1221
Advances in pediatric bone marrow transplantation (BMT) are slowed by the small number of patients with a given disease who undergo transplantation, a lack of sufficient infrastructure to run early-phase oncology protocols and studies of rare nonmalignant disorders, and challenges associated with funding multi-institutional trials. Leadership of the Pediatric Blood and Marrow Transplant Consortium (PBMTC), a large pediatric BMT clinical trials network representing 77 active and 45 affiliated centers worldwide, met in April 2009 to develop strategic plans to address these issues. Key barriers, including infrastructure development and funding, along with scientific initiatives in malignant and nonmalignant disorders, cellular therapeutics, graft-versus-host disease, and supportive care were discussed. The PBMTC's agenda for approaching these issues will result in infrastructure and trials specific to pediatrics that will run through the PBMTC or its partners, the Blood and Marrow Transplant Clinical Trials Network and the Children's Oncology Group.
View details for DOI 10.1016/j.bbmt.2009.12.536
View details for Web of Science ID 000281304000002
View details for PubMedID 20079865
Pre-stem cell transplantation enzyme replacement therapy in Hurler syndrome does not lead to significant antibody formation or delayed recovery of the endogenous enzyme post-transplant: A case report
2007; 11 (5): 563-567
Combined enzyme replacement therapy (ERT) and stem cell transplant (SCT) were done for a two year old boy with severe Hurler syndrome(HS) with the aim to decrease transplant related complications. He tolerated both the procedures well without any major complications. Urine glycosaminoglycans (GAGs) decreased post-transplant and child has improved clinically and neurologically. Insignificant titers of the anti-iduronidase antibodies which developed post-transplant did not affect the transplant outcome or the endogenous recovery of the alpha-L-iduronidase enzyme.
View details for DOI 10.1111/j.1399-3046.2007.00720.x
View details for Web of Science ID 000248177400021
View details for PubMedID 17631030