Mitchell Horwitz

Overview:

Allogeneic stem cell transplantation using umbilical cord blood grafts; Allogenic stem cell transplantation for Sickle Cell Disease; Prevention of acute graft versus host disease through donor stem cell graft manipulation; Improving immune recovery following alternative donor stem cell transplantation using donor graft manipulation or third party thymus transplantation.

Positions:

Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Affiliate of the Duke Regeneration Center

Regeneration Next Initiative
School of Medicine

Education:

M.D. 1992

Rush University

Medical Resident, Medicine

Northwestern University

Grants:

A Phase 2/3, Multicenter, randomized, double-blind, placebo-controlled, study to evaluate the safety and efficacy of Alpha-! Antitrypsin for the Prevention of GVHD

Administered By
Duke Cancer Institute
Awarded By
CSL Behring LLC
Role
Principal Investigator
Start Date
End Date

A phase III Randomized Open-Label Multi-Center study of ruxolitinib vs. best available therapy in patients with corticosteroid-refractory chronic graft vs host disease after allogenic stem cell transplantation

Administered By
Duke Cancer Institute
Awarded By
Incyte Corporation
Role
Principal Investigator
Start Date
End Date

A Blinded, Prospective Non-Interventional Observational Study for the Evaluation of a GVHD Negative Outcome Score (GNOS) in Matched Unrelated or Haploidentical Hematopoietic Stem Cell Transplant

Administered By
Duke Cancer Institute
Awarded By
Washington University in St. Louis
Role
Principal Investigator
Start Date
End Date

A Multicenter, Randomized, Phase III Registratoin Trial of Transplantation of NiCord, Ex Vivo Expanded, Umbilical Cord Blood-derived, Stem and Progenitor Cells, versus Unmanipulated Umbilical Cord Blood for patients with Hematological Malignancies

Administered By
Duke Cancer Institute
Awarded By
Gamida Cell Ltd
Role
Principal Investigator
Start Date
End Date

A Randomized, Phase II, Multicenter, Open Label, Study Evaluating Sirolimus and Prednisone in Patients with Refined Minnesota Standard Risk, Ann Arbor 1/2 Confirmed Acute Graft-Versus-Host Disease (GMT CTN Protocol 1501

Administered By
Duke Cancer Institute
Awarded By
National Marrow Donor Program
Role
Principal Investigator
Start Date
End Date

Publications:

Health-Related Quality of Life Following Allogeneic Hematopoietic Stem Cell Transplantation with Omidubicel Versus Standard Umbilical Cord Blood

Authors
Lin, C; Sajeev, G; Stiff, P; Brunstein, C; Cutler, C; Sanz, G; Lindemans, C; Rezvani, A; Hanna, R; Koh, LP; Maziarz, R; Hwang, W; Song, Y; Liu, Q; Manghani, R; Sivaraman, S; Signorovitch, J; Galamidi-Cohen, E; Horwitz, M; Sung, A
URI
https://scholars.duke.edu/individual/pub1525449
Source
manual
Published Date

Multicenter Long-Term Follow Up of Allogeneic Hematopoietic Stem Cell Transplantation with Omidubicel: A Pooled Analysis of Five Prospective Clinical Trials

Authors
Lin, C; Schwarzbach, A; Montesinos, P; Stiff, P; Cutler, C; Parikh, S; Brunstein, C; Lindemans, C; Hanna, R; Koh, LP; Maziarz, R; Keating, A; Hwang, W; Rezvani, A; Valcarcel, D; Fernandes, J; Badell, I; Jagasia, M; Frankfurt, O; Ram, R; McGuirk, J; Kurtzberg, J; Sanz, G; Simantov, R; Horwitz, M
URI
https://scholars.duke.edu/individual/pub1525450
Source
manual
Published Date

Geriatric Assessment Reveals Actionable Impairments in Hematopoietic Stem Cell Transplantation Candidates Age 18 to 80 Years.

Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for both malignant and nonmalignant hematologic diseases; however, reported rates of treatment-related mortality approach 30%. Outcomes are worse in patients who begin HCT with functional impairments. To detect such impairments, a geriatric assessment (GA) is recommended in adults age ≥65 years. Younger HCT candidates also may be impaired because of chemotherapy regimens pre-HCT. Therefore, we hypothesized that GA can be beneficial for adult patients of all ages and subsequently created a clinical pretransplantation optimization program to assess all HCT candidates using a modified GA. One-hundred fifty-seven patients were evaluated in 4 functional domains- physical, cognitive, nutritional, and psychological-at 2 time points prior to HCT-new patient evaluation (NPE) and sign-off (SO)-between October 2017 and January 2020. At NPE, 80.9% of the patients had at least 1 domain with a functional impairment, and physical (P = .006), cognitive (P = .04), and psychological (P = .04) impairments were associated with an increased likelihood of not proceeding to HCT. In addition, patients age 18 to 39 years were more likely than older patients to have a physical function impairment (P = .001). Between NPE and SO, 51.9% of the patients had resolution of 1 or more impairments, and nutritional impairment at SO was predictive of worse overall survival (P = .01). Our study shows that GA can identify functional impairments in patients of all ages. Early identification of impairments could facilitate referrals to supportive care and resolution of impairments prior to HCT, suggesting that GA could be recommended for HCT candidates of all ages.
Authors
Lew, MV; Ren, Y; Lowder, YP; Siamakpour-Reihani, S; Ramalingam, S; Romero, KM; Thompson, JC; Bohannon, LM; McIntyre, J; Tang, H; Van Opstal, J; Johnson, E; Cohen, HJ; Bartlett, DB; Pastva, AM; Morey, M; Hall, KS; Smith, P; Peters, KB; Somers, TJ; Kelleher, S; Smith, SK; Wischmeyer, PE; Lin, P-H; Wood, WA; Thorpe, G; Minor, K; Wiggins, K; Hennig, T; Helms, T; Welch, R; Matthews, B; Liu, J; Burleson, J; Aberant, T; Engemann, AK; Henshall, B; Darby, M; Proch, C; Dellascio, M; Pittman, A; Suminguit, J; Choi, T; Gasparetto, C; Long, GD; Lopez, RD; Sarantopoulos, S; Horwitz, ME; Chao, NJ; Sung, AD
MLA Citation
Lew, Meagan V., et al. “Geriatric Assessment Reveals Actionable Impairments in Hematopoietic Stem Cell Transplantation Candidates Age 18 to 80 Years.Transplant Cell Ther, vol. 28, no. 8, Aug. 2022, pp. 498.e1-498.e9. Pubmed, doi:10.1016/j.jtct.2022.05.018.
URI
https://scholars.duke.edu/individual/pub1521437
PMID
35595226
Source
pubmed
Published In
Transplant Cell Ther
Volume
28
Published Date
Start Page
498.e1
End Page
498.e9
DOI
10.1016/j.jtct.2022.05.018

Haploidentical bone marrow transplantation in patients with relapsed or refractory severe aplastic anaemia in the USA (BMT CTN 1502): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Relapsed severe aplastic anaemia is a marrow failure disorder with high morbidity and mortality. It is often treated with bone marrow transplantation at relapse post-immunosuppressive therapy, but under-represented minorities often cannot find a suitably matched donor. This study aimed to understand the 1-year overall survival in patients with relapsed or refractory severe aplastic anaemia after haploidentical bone marrow transplantation. METHODS: We report the outcomes of BMT CTN 1502, a single-arm, phase 2 clinical trial done at academic bone marrow transplantation centres in the USA. Included patients were children and adults (75 years or younger) with severe aplastic anaemia that was refractory (fulfilment of severe aplastic anaemia disease criteria at least 3 months after initial immunosuppressive therapy) or relapsed (initial improvement of cytopenias after first-line immunosuppressive therapy but then a later return to fulfilment of severe aplastic anaemia disease criteria), adequate performance status (Eastern Cooperative Oncology Group score 0 or 1, Karnofsky or Lansky score ≥60%), and the presence of an eligible related haploidentical donor. The regimen used reduced-intensity conditioning (rabbit anti-thymocyte globulin 4·5 mg/kg in total, cyclophosphamide 14·5 mg/kg daily for 2 days, fludarabine 30 mg/kg daily for 5 days, total body irradiation 200 cGy in a single fraction), related HLA-haploidentical donors, and post-transplantation cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. Additionally, for GVHD prophylaxis, mycophenolate mofetil was given orally at a dose of 15 mg/kg three times a day up to 1 g three times a day (maximum dose 3000 mg per day) from day 5 to day 35, and tacrolimus was given orally or intravenously from day 5 to day 180 as per institutional standards to maintain a serum concentration of 10-15 ng/mL. The primary endpoint was overall survival 1 year after bone marrow transplantation. All patients treated per protocol were analysed. This study is complete and is registered with ClinicalTrials.gov, NCT02918292. FINDINGS: Between May 1, 2017, and Aug 30, 2020, 32 patients with relapsed or refractory severe aplastic anaemia were enrolled from 14 centres, and 31 underwent bone marrow transplantation. The median age was 24·9 years (IQR 10·4-51·3), and median follow-up was 24·3 months (IQR 12·1-29·2). Of the 31 patients who received a transplant, 19 (61%) were male and 12 (39%) female. 13 (42%) patients were site-reported as non-White, and 19 (61%) were from under-represented racial and ethnic groups; there were four (13%) patients who were Asian, seven (23%) Black, one (3%) Hawaiian/Pacific Islander, and one (3%) more than one race, with seven (23%) patients reporting Hispanic ethnicity. 24 (77%) of 31 patients were alive with engraftment at 1 year, and one (3%) patient alive with autologous recovery. The 1-year overall survival was 81% (95% CI 62-91). The most common grade 3-5 adverse events (seen in seven or more patients) included seven (23%) patients with abnormal liver tests, 15 (48%) patients with cardiovascular changes (including sinus tachycardia, heart failure, pericarditis), ten (32%) patients with gastrointestinal issues, seven (23%) patients with nutritional disorders, and eight (26%) patients with respiratory disorders. Six (19%) deaths, due to disease and unsuccessful bone marrow transplantation, were reported after transplantation. INTERPRETATION: Haploidentical bone marrow transplantation using this approach results in excellent overall survival with minimal GVHD in patients who have not responded to immunosuppressive therapy, and can expand access to bone marrow transplantation across all populations. In clinical practice, this could now be considered a standard approach for salvage treatment of severe aplastic anaemia. Attention to obtaining high cell doses (>2·5 × 108 nucleated marrow cells per kg of recipient ideal bodyweight) from bone marrow harvests is crucial to the success of this approach. FUNDING: US National Heart, Lung, and Blood Institute and US National Cancer Institute.
Authors
DeZern, AE; Eapen, M; Wu, J; Talano, J-A; Solh, M; Dávila Saldaña, BJ; Karanes, C; Horwitz, ME; Mallhi, K; Arai, S; Farhadfar, N; Hexner, E; Westervelt, P; Antin, JH; Deeg, HJ; Leifer, E; Brodsky, RA; Logan, BR; Horowitz, MM; Jones, RJ; Pulsipher, MA
URI
https://scholars.duke.edu/individual/pub1530263
PMID
35907408
Source
pubmed
Published In
The Lancet Haematology
Published Date
DOI
10.1016/S2352-3026(22)00206-X

Impact of Center Experience with Donor Type on Outcomes: A Secondary Analysis, Blood and Marrow Transplant Clinical Trials Network 1101Open for Accrual June 2012Open for Accrual June 2012.

We previously reported the results of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1101, a randomized comparison of hematopoietic cell transplantation (HCT) performed with double umbilical cord blood units (dUCB) or with haploidentical bone marrow (haplo-BMT) with post-transplantation cyclophosphamide (PTCy) in the nonmyeloablative setting. Those results showed similar progression-free survival in the 2 treatment groups but lower nonrelapse mortality and better overall survival in the haplo-BM arm. In this secondary analysis, we sought to investigate whether transplantation center's previous experience with haplo-BM and/or dUCB HCT had an impact on outcomes. All patients randomized in BMT CTN 1101 were included. Center experience was assigned based on the number of transplantations with each platform performed in the year before initiation of the study according to the Center for International Blood and Marrow Transplant Research. Centers were then classified as a dUCB center (>10 dUCB HCTs; n = 117 patients, 10 centers), a haplo-BM center (>10 haplo-BM HCTs and ≤10 dUCB HCTs; n = 110 patients, 2 centers), or other center (≤10 haplo and ≤10 dUCB HCTs; n = 140 patients, 21 centers). After adjusting for age, Karnofsky Performance Status, and Disease Risk Index, we found that haplo-BM centers had lower overall mortality with this donor type compared with dUCB centers (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.44 to 4.56). In contrast, there were no differences in overall mortality between haplo-BM and dUCB in centers that were experienced with dUCB HCT (HR, 1.02; 95% CI, .59 to 1.79) or had limited to no experience with either dUCB or haplo-BM HCT (HR, 1.36; 95% CI, .83 to 2.21). The higher risk of treatment failure and overall mortality in dUCB HCT in haplo BM-experienced centers was driven by a significantly higher risk of relapse (HR, 1.78; 95% CI, 1.07 to 2.97). With the exception of worse outcomes among dUCB HCT recipients in haplo-BM centers, transplantation center experience in the year before initiation of BMT CTN 1101 had a limited impact on the outcomes of this randomized clinical trial.
Authors
Brunstein, CG; O'Donnell, PV; Logan, B; Dawson, P; Costa, L; Cutler, C; Craig, M; Hogan, W; Horowitz, MM; Horwitz, ME; Karanes, C; Magenau, JM; Malone, A; McCarty, J; McGuirk, JP; Morris, LE; Rezvani, AR; Salit, R; Vasu, S; Eapen, M; Fuchs, EJ; Blood and Marrow Transplant Clinical Trials Network,
MLA Citation
Brunstein, Claudio G., et al. “Impact of Center Experience with Donor Type on Outcomes: A Secondary Analysis, Blood and Marrow Transplant Clinical Trials Network 1101Open for Accrual June 2012Open for Accrual June 2012.Transplantation and Cellular Therapy, vol. 28, no. 7, July 2022, pp. 406.e1-406.e6. Epmc, doi:10.1016/j.jtct.2022.03.024.
URI
https://scholars.duke.edu/individual/pub1516003
PMID
35390529
Source
epmc
Published In
Transplantation and Cellular Therapy
Volume
28
Published Date
Start Page
406.e1
End Page
406.e6
DOI
10.1016/j.jtct.2022.03.024