Monica Davini

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• Davini, M., Angulo, P., Elkus, H., Grace, R. F., Buissereth, T., Bennett, C., Rifkin-Zenenberg, S., Gunn, E. R., Lebensburger, J. D., Rankin, A. W., Nakano, T. A., Schultz, C. L., Pinchinat, A., Hillier, K., & Badawy, S. M. (2022). Standardizing the Diagnostic and Therapeutic Approach to Newly Diagnosed Children with ITP: Prospective Data from the ITP Consortium of North America (ICON) Quality Improvement Initiative. Blood, 140(Supplement 1), 1208-1210. doi:10.1182/blood-2022-170067
• Proytcheva, M., Maza, M. d., Davini, M., Hanmod, S., Pariury, H., Truscott, L., Katsanis, E., Sapp, L., & Staples, K. (2022). Busulfan Fludarabine and Melphalan is effective conditioning for pediatric and young adult patients with myeloid malignancies underdoing matched sibling or alternative donor transplantation. Pediatric Blood & Cancer. doi:10.21203/rs.3.rs-1717185/v1
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  Abstract Background: Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for patients with high-risk myeloid malignancies. Objectives : We reviewed our ten-year experience (October 2012 thru October 2021) of allo-HCT in patients with myeloid malignancies treated on the pediatric HCT service and conditioned with myeloablative targeted dose-busulfan (BU), fludarabine (FLU) and melphalan (MEL). Study Design: Twenty-three children, adolescents, and young adult patients (CAYA) (median age 15.4 years, range 0.6 to 27.2) with acute myeloid leukemia (AML) (n=17), myelodysplastic syndrome (MDS) (n=4), or chronic myeloid leukemia (CML) (n=2) underwent allo-HCT conditioned with BU-FLU-MEL. Four patients had treatment-related AML/MDS, following osteogenic and Ewing sarcoma (t-AML, n=2) and acute lymphoblastic leukemia (t-MDS, n=2). Donor/stem cell source was matched sibling donor (MSD) peripheral blood stem cells (PBSC) (n=7), matched unrelated donor (MUD) PBSC (n=2), unrelated single (n=1) or double umbilical cord blood (UCB) (n=2) or haploidentical donor bone marrow (haplo-BMT) (n=11). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine-methotrexate (CSA-MTX) for MSD and MUD, and CSA-mycophenolate mofetil (MMF) for unrelated UCB transplants. Patients undergoing T-cell replete haplo-BMT received post-transplant cyclophosphamide (PT-CY) (n=7) or cyclophosphamide and bendamustine PT-CY/BEN (n=4) with tacrolimus and MMF. Thirteen patients with of AML were in first remission (CR1) with seven being minimal residual disease negative (MRD - ), three patients in second remission (CR2) with two MRD - , and five patients had received no treatment prior to allo-HCT (MDS, n=4 and AML evolved from del(7q) MDS). Risk stratification based on remission/MRD status, cytogenetics and age was low (n=2), intermediate (n=15), high (=3) and very high risk (n=1). The two patients with CML had failed tyrosine kinase inhibitor therapies. Results: With a median follow-up of 37.2 months the relapse rate is only 4.5% with a remarkable overall survival (OS) of 100%, progression-free survival (PFS) of 95.5% and graft-versus-host-free relapse-free survival (GRFS) of 67.8%. The donor source and the graft-versus-host-disease (GvHD) prophylaxis regimen significantly impacted the cumulative incidence of grades II-IV acute GvHD (aGvHD) 66.7% versus 18.2% ( P=0.03 ) and chronic GvHD (cGvHD) 66.7% versus 0% ( P=0.001 ) in the patients receiving MSD or MUD PBSC compared to haplo-BMT respectively. This resulted in significantly improved GRFS in haplo-BMT recipients of 83.3% compared to 40% in patients receiving related or unrelated matched donor PBSC transplantation ( P=0.025 ). Conclusions: Our results demonstrate that BU-FLU-MEL is an efficacious conditioning regimen for disease control in young patients with myeloid malignancies undergoing matched sibling or alternative donor hematopoietic cell transplantation but in the setting of PBSC grafts with CSA-MTX GvHD prophylaxis it results in an unacceptably high incidence of GvHD.
• Staples, K., Sapp, L. N., Truscott, L., Pariury, H., Hanmod, S., Davini, M., de la Maza, M., Proytcheva, M., Katsanis, E., Staples, K., Sapp, L. N., Truscott, L., Pariury, H., Hanmod, S., Davini, M., de la Maza, M., Proytcheva, M., Katsanis, E., Katsanis, E., , Proytcheva, M., et al. (2022). Busulfan, fludarabine, and melphalan are effective conditioning for pediatric and young adult patients with myeloid malignancies underdoing matched sibling or alternative donor transplantation. Pediatric Blood & Cancer, 70(2). doi:10.1002/pbc.30102
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  Abstract: Background Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for patients with high-risk myeloid malignancies. Procedure We present our 10-year experience (October 2012 to October 2021) of consecutive allo-HCT in patients with myeloid malignancies treated on the pediatric HCT service and conditioned with myeloablative targeted dose—busulfan (BU), fludarabine (FLU), and melphalan (MEL). Twenty-three children, adolescents, and young adult patients (CAYA) (median age 15.4 years) with acute myeloid leukemia (AML, n = 17), myelodysplastic syndrome (MDS, n = 4), or chronic myeloid leukemia (CML, n = 2) underwent allo-HCT post-BU-FLU-MEL. Four patients had treatment-related AML/MDS. Donor/stem cell source was matched sibling donor (MSD) PBSC (n = 7), matched unrelated donor (MUD) PBSC (n = 2), umbilical cord blood (UCB) (n = 3), or haploidentical-BMT (n = 11). Risk stratification was low (n = 2), intermediate (n = 15), high (n = 3), and very high risk (n = 1). The two patients with CML had failed tyrosine kinase inhibitor therapies. Results With a median follow-up of 41.6 months, the relapse rate is only 4.5% with an overall survival (OS) 100%, progression-free survival (PFS) 95.5%, and graft-versus-host-free-relapse-free survival (GRFS) 67.8%. The donor source and the acute graft-versus-host disease (GvHD) prophylaxis regimen significantly impacted grade II–IV aGvHD 66.7% versus 19.2% (p = .039) and chronic graft-versus-host-disease (cGvHD) 66.7% versus 0% (p = .002) in the patients receiving MSD or MUD PBSC compared to haplo-BMT, respectively, resulting in improved GRFS in haplo-BMT, 83.3% compared to 40% matched donor peripheral blood stem cell transplant (PBSCT) (p = .025). Conclusions Our results demonstrate that BU-FLU-MEL is efficacious conditioning for disease control in young patients with myeloid malignancies undergoing MSD or alternative donor allo-HCT, but in the setting of PBSC grafts with cyclosporine A-methotrexate (CSA-MTX) GvHD prophylaxis, it results in an unacceptably high incidence of GvHD.
• Davini, M., Shiah, K., & Agrawal, A. (2020). Negative initial bone marrow aspirate does not rule out acute lymphoblastic leukemia. Presented at ASPHO. doi:10.22541/au.160902293.31389727/v1