Project 6 Project 6 proposes novel clinical trials to reduce non-leukemic mortality associated with allogenic HSCT for treatment of leukemias and myelodysplasia (MDS), particularly in older patients and in patients lacking an HLA-matched sibling donor and to treat post transplantation viral disease and leukemic relapse. There are 6 clinical trials under 2 specific aims.
Aim1 includes 3 phase II clinical trials of TCD grafts to speed marrow and immune reconstitution.
Aim 1 A will evaluate the ability of TCD-PBSC (CliniMACS) given after one of 2 reduced intensity regimens using only chemotherapy, as compared to our standard high intensity, TBI containing regimen to secure consistent engraftment, low rates of GVHD, TRM and relapse and high DFS.
Aim 1 8 clinically translates Dr. van den Brink's studies done during this grant period to use palifermin and leuprolide to protect the thymic stroma and promote early, robust recovery of T cell immunity, thereby reducing TRM due to infection in older patients (median age >50).
Aim I C, also derived from trials conducted in the current grant, will evaluate whether addition of haplotype disparate TCD-PBSC to a double cord blood (CB) graft provides earlier hematopoietic reconstitution, thereby reducing early TRM while maintaining the low incidence of relapse observed following double CB grafts.
Aim 2 includes 3 trials of adoptive cellular therapy. Effective prevention of GVHD, as developed at our center, allows for adoptive cell therapies in the absence of post-transplant immuno-suppressive drugs to prevent GVHD.
Aim 2 A is a 2- armed Phase II extension ofthe Phase I trial conducted in the current grant period to evaluate treatment of CMV infections with a) CMVpp65-specific T-cells derived from seropositive HSCT donors of b) partially HLA matched 3rd party CMV-CTL for patients receiving CBs or transplants from CMV seronegative donors.
Aim 2 B derives from studies conducted in the current grant and extends our Phase I trial of single dose WT1 -CTL to multiple dosing for treatment of patients with recurrence of WT-1 + leukemias.
Aim I C is a phase I trial of donor-derived EBV-CTL transduced to express a CD19-specific chimeric antigen receptor for the treatment of GDI 9+ leukemias.

Public Health Relevance

These trials test novel transplant and post transplant strategies which show promise of improving prospects for sustained DFS in adults and children with acute leukemia, MDS and lymphoma, particularly older patients and patients lacking an HLA matched sibling donor. They will also test adoptive therapies which may be broadly applied to patients with severe viral infection or leukemia relapse.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Boudreau, Jeanette E; Hsu, Katharine C (2018) Natural Killer Cell Education and the Response to Infection and Cancer Therapy: Stay Tuned. Trends Immunol 39:222-239
Lin, Richard J; Ho, Caleb; Hilden, Patrick D et al. (2018) Allogeneic haematopoietic cell transplantation impacts on outcomes of mantle cell lymphoma with TP53 alterations. Br J Haematol :
Malard, Florent; Labopin, Myriam; Cho, Christina et al. (2018) Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC. J Hematol Oncol 11:127
Luduec, Jean-BenoƮt Le; Kudva, Anupa; Boudreau, Jeanette E et al. (2018) Novel multiplex PCR-SSP method for centromeric KIR allele discrimination. Sci Rep 8:14853
Shah, Gunjan L; Moskowitz, Craig H (2018) Transplant strategies in relapsed/refractory Hodgkin lymphoma. Blood 131:1689-1697
Avanzi, Mauro P; Yeku, Oladapo; Li, Xinghuo et al. (2018) Engineered Tumor-Targeted T Cells Mediate Enhanced Anti-Tumor Efficacy Both Directly and through Activation of the Endogenous Immune System. Cell Rep 23:2130-2141
Staffas, Anna; Burgos da Silva, Marina; Slingerland, Ann E et al. (2018) Nutritional Support from the Intestinal Microbiota Improves Hematopoietic Reconstitution after Bone Marrow Transplantation in Mice. Cell Host Microbe 23:447-457.e4
Velardi, Enrico; Tsai, Jennifer J; Radtke, Stefan et al. (2018) Suppression of luteinizing hormone enhances HSC recovery after hematopoietic injury. Nat Med 24:239-246
Moskowitz, Craig H (2018) Should all patients with HL who relapse after ASCT be considered for allogeneic SCT? A consult, yes; a transplant, not necessarily. Blood Adv 2:821-824
Kim, Seong Jin; Huang, Yao-Ting; Foldi, Julia et al. (2018) Cytomegalovirus resistance in CD34+ -selected hematopoietic cell transplant recipients. Transpl Infect Dis 20:e12881

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