Santosh S Hanmod

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• Davini, M., Hanmod, S., Katsanis, E., Maza, M. d., Pariury, H., Proytcheva, M., Sapp, L., Staples, K., & Truscott, L. (2022). Busulfan Fludarabine and Melphalan is effective conditioning for pediatric and young adult patients with myeloid malignancies underdoing matched sibling or alternative donor transplantation. Authorea - Authorea. doi:10.22541/au.166306143.35876717/v1
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  Background: Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for patients with high-risk myeloid malignancies. Procedure: We present our ten-year experience (October 2012-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 15.4yr) 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 MSD PBSC (n=7), MUD PBSC (n=2), UCB (n=3) or haploidentical-BMT (n=11). Risk stratification 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 39.6 months the relapse rate is only 4.5% with an OS 100%, PFS 95.5% and graft-versus-host-free-relapse-free survival (GRFS) 67.8%. The donor source and the GvHD prophylaxis regimen significantly impacted grades II-IV aGvHD 66.7% versus 19.2% ( P=0.039 ) and cGvHD 66.7% versus 0% ( P=0.002 ) in the patients receiving matched sibling (MSD) or matched unrelated donor (MUD) PBSC compared to haplo-BMT respectively, resulting in improved GRFS in haplo-BMT, 83.3% compared to 40% matched donor PBSCT ( P=0.025 ). 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 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. (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.
• Stanley, K., Simpson, R. J., Katsanis, E., & Hanmod, S. (2021). Haploidentical hematopoietic cell transplantation is even more advantageous during the COVID-19 pandemic.. Pediatric transplantation, 25(3), e14004. doi:10.1111/petr.14004
• Hanmod, S., Jesudas, R., Kulkarni, R., & Chitlur, M. (2016). Neonatal Hemostatic Disorders: Issues and Challenges. Seminars in Thrombosis and Hemostasis, 42(7). doi:10.1055/s-0036-1593415
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  Neonates form a unique cohort with distinct features associated with the hemostatic system compared with older children and adults. The development of the human hemostatic system begins around 10 weeks in utero and continues to evolve during childhood. This dynamic period termed developmental hemostasis should be taken into consideration when diagnosing a neonate with disorders of bleeding or thrombosis.
• Hanmod, S., Wang, G., Edwards, H., Buck, S., Ge, Y., Taub, J., & Wang, Z. (2015). Targeting histone deacetylases (HDACs) and Wee1 for treating high-risk neuroblastoma. Pediatric Blood and Cancer, 62(1). doi:10.1002/pbc.25232
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  Background: Despite advances in treatment regimens, patients with high-risk neuroblastoma have long-term survival rates of
• Chemaly, R., Hanmod, S., Jiang, Y., Rathod, D., Mulanovich, V., Adachi, J., Rolston, K., Raad, I., & Hachem, R. (2009). Tigecycline use in cancer patients with serious infections: A report on 110 cases from a single institution. Medicine, 88(4). doi:10.1097/MD.0b013e3181af01fc
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  Tigecycline, the first in a new class of glycylcyclines, has been approved for the treatment of complicated skin and skin structure and intraabdominal infections in adults. However, clinical data on its safety and effectiveness in cancer patients are lacking. We reviewed the records of all cancer patients treated with tigecycline for more than 48 hours between June 2005 and September 2006 at our institution and identified 110 consecutive cases (median age, 58 yr; range, 18-81 yr). We collected data on demographics, cancer type, tigecycline indication, microbiologic characteristics, side effects, and outcome. Sixty-four (58%) patients had hematologic malignancies; 27 patients had undergone hematopoietic stem cell transplantation. Thirty-one (28%) patients had neutropenia, and 62 (56%) were in the intensive care unit at the start of therapy. Most patients (106 [96%]) received tigecycline as a second-line agent (after not responding to other broad-spectrum antibiotics), and 101 (92%) received it in combination with an antipseudomonal drug. The mean duration of therapy was 11 days (range, 3-35 d). Sixty-six (60%) patients received tigecycline for refractory pneumonia, 19 (17%) had bacteremia, 9 (8%) had intraabdominal infections, and 7 (6%) had complicated skin and soft tissue infections. Fifty (45%) patients had microbiologically documented infections, and the remaining patients had negative cultures at the start of therapy.An overall clinical response was noted in 70 (64%) patients. More clinical responses were seen in patients with bacteremia than in those with pneumonia (79% vs. 51%; p = 0.029). Patients with microbiologically documented infections had significantly higher clinical response rates than patients with non-microbiologically documented infections (73% vs. 55%; p = 0.047). Forty (36%) patients did not respond to treatment; 36 of these patients died of active infection during tigecycline therapy. Patients with pneumonia had a significantly higher mortality rate than patients with bacteremia (44% vs. 16%; p = 0.026). During the 60 days of follow-up from the date of clinical response, patients with pneumonia had significantly shorter survival durations than patients with other infections. Of the 42 patients who were not on antiemetics or ventilator support at the start of tigecycline therapy, 2 (5%) experienced mild nausea, and 1 (2%) experienced nausea and vomiting. Only 4 (4%) patients overall experienced diarrhea during tigecycline therapy, all of whose stools were negative for Clostridium difficile toxin. No serious adverse events related to tigecycline use were identified. The combination of tigecycline and an antipseudomonal drug may be appropriate for treating refractory infections and multidrug-resistant organisms in cancer patients, including hematopoietic stem cell transplant recipients. Patients with refractory pneumonia had a relatively low clinical response rate in our study. Copyright © 2009 by Lippincott Williams & Wilkins.