Paul Martin

Overview:

For most of my career in Pediatric Hematology/Oncology I have focused on the use of stem cell transplant for the treatment of pediatric leukemias (ALL, AML, CML and JMML) and other non-malignant blood disorders, such as sickle cell disease, hemaphagocytic disorders, Wiskott-Aldrich, aplastic anemia, Diamond-Blackfan Anemia, as well as inherited metabolic diseases. In addition to focusing on determining the best use of stem cell transplants for these disorders, I have also been involved in clinical research investigating the prevention and treatment of transplant related morbidity, particularly veno-occlusive disease of the liver, infections and diffuse alveolar hemorrhage. As study chair for the Children's Oncology Group protocol 9904, I was involved in the development, implementation and analysis of a large, international frontline study of childhood acute lymphoblastic leukemia. Results from this study show that a significant number of children with certain favorable cytogenetic abnormalities in their leukemic cells and who have a rapid response to their initial chemotherapy can expect to have a >95% chance of cure when treated with relatively low intensity chemotherapy.  

I have concentrated on providing high quality care for high risk leukemia patients who require high intensity therapies, such as stem cell transplant and immunotherapy.  As a member of the Pediatric Transplant and Cellular Therapy Division I provide clinical care for these patients.  As a member of various cooperative groups and local PI for several drug trials, I have worked to provide better care and more specific therapies for the toxicities associated with stem cell transplant.  

I have also collaborated with the Pediatric Immunology Division to provide a life-saving therapy for a small group of patients with thymic dysfunction, which causes severe immunodeficiency.  Our clinical team now provides support during these patients hospital admissions for donor thymus tissue implantation.

Positions:

Professor of Pediatrics

Pediatrics, Transplant and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1987

Washington University in St. Louis

Ph.D. 1987

Washington University in St. Louis

Intern, Pediatrics

Yale University

Resident, Pediatrics

Yale University

Fellow, Pediatric Hematology/Oncology, Pediatrics

Yale University

Grants:

Pediatric Oncology Group (POG)

Administered By
Pediatrics, Transplant and Cellular Therapy
Awarded By
National Institutes of Health
Role
Investigator
Start Date
End Date

A Phase II, single arm, multicenter trial to determine the efficacy and safety of CTL019 in pediatric patients with relapsed and refractory B-cell acute lymphoblastic leukemia

Administered By
Pediatrics, Transplant and Cellular Therapy
Awarded By
Novartis Pharmaceuticals Corporation
Role
Principal Investigator
Start Date
End Date

A Phase 3, Randomized, Adaptive Study Comparing the Efficacy and Safety of Defibrotide vs Best Supportive Care in the Prevention of Hepatic Veno-Occlusive Disease in Adult and Pediatric Patients Undergoing Hematopoietic Stem Cell Transplant

Administered By
Pediatrics, Transplant and Cellular Therapy
Awarded By
Jazz Pharmaceuticals
Role
Principal Investigator
Start Date
End Date

PBMTC SUP 1601 Pathogen Identification in Pediatric HSCT

Administered By
Pediatrics, Transplant and Cellular Therapy
Awarded By
Children's Hospital Los Angeles
Role
Principal Investigator
Start Date
End Date

A Phase 2 Multicenter Single arm Study of Moxetumomab Pasudotox in Pediatric Subjects with Relapsed or Refractory pALL

Administered By
Pediatrics, Transplant and Cellular Therapy
Awarded By
MedImmune, Inc.
Role
Principal Investigator
Start Date
End Date

Publications:

Sickle Cell Transplantation Evaluation of Long-term and Late Effects Registry (STELLAR) to Compare Long-term Outcomes After Hematopoietic Cell Transplantation to Those in Siblings Without Sickle Cell Disease and in Nontransplanted Individuals With Sickle

BACKGROUND: There are sparse data on the long-term and late effects of hematopoietic cell transplantation (HCT) for sickle cell disease (SCD). OBJECTIVE: This study aims to establish an international registry of long-term outcomes post-HCT for SCD and demonstrate the feasibility of recruitment at a single site in the United States. METHODS: The Sickle Cell Transplantation Evaluation of Long-Term and Late Effects Registry (STELLAR) was designed to enroll patients with SCD ≥1 year post-HCT, their siblings without SCD, and nontransplanted controls with SCD to collect web-based participant self-reports of health status and practices by using the Bone Marrow Transplant Survivor Study (BMTSS) surveys, health-related quality of life (HRQOL) using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Profile-25 or Pediatric Profile-29 survey, chronic graft-versus-host disease (cGVHD) using the symptom scale survey, daily pain using an electronic pain diary, the economic impact of HCT using the financial hardship survey, sexual function using the PROMIS Sexual Function SexFSv2.0 survey, and economic productivity using the American Time Use Survey (ATUS). We also piloted retrieval of clinical data previously submitted to the Center for International Blood and Marrow Transplant Research (CIBMTR); recorded demographics, height, weight, blood pressure, waist and hip circumferences, timed up and go (TUG) test, and handgrip test; and obtained blood for metabolic screening, gonadal function, fertility potential, and biorepository of plasma, serum, RNA, and DNA. RESULTS: Of 100 eligible post-HCT patients, we enrolled 72 (72%) participants aged 9-38 (median 17) years. We also enrolled 19 siblings aged 5-32 (median 10) years and 28 nontransplanted controls with SCD aged 4-46 (median 22) years. Of the total 119 participants, 73 (61%) completed 85 sets of surveys and 41 (35%) contributed samples to the biorepository. We completed ATUS interviews of 28 (24%) participants. We successfully piloted retrieval of data submitted to the CIBMTR and expanded recruitment to multiple sites in the United States, Canada, the United Kingdom, and Nigeria. CONCLUSIONS: It is feasible to recruit subjects and conduct study procedures for STELLAR in order to determine the long-term and late effects of HCT for SCD. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36780.
Authors
Krishnamurti, L; Arnold, SD; Haight, A; Abraham, A; Guilcher, GM; John, T; Bakshi, N; Shenoy, S; Syrjala, K; Martin, PL; Chaudhury, S; Eames, G; Olowoselu, OF; Hsieh, M; De La Fuente, J; Kasow, KA; Stenger, E; Mertens, A; El-Rassi, F; Lane, P; Shaw, BE; Meacham, L; Archer, D
URI
https://scholars.duke.edu/individual/pub1526777
PMID
35793124
Source
pubmed
Published In
Jmir Research Protocols
Volume
11
Published Date
Start Page
e36780
DOI
10.2196/36780

Risk Factors for CMV Viremia and Treatment-Associated Adverse Events Among Pediatric Hematopoietic Stem Cell Transplant Recipients.

BACKGROUND: Cytomegalovirus (CMV) causes substantial morbidity and mortality after hematopoietic stem cell transplantation (HSCT). There are limited data on risk factors for CMV viremia and the safety of antiviral medications used to treat CMV in children. METHODS: We conducted a single-center retrospective study of children who underwent HSCT between 2000 and 2016. We used log-logistic regression to evaluate associations between clinical characteristics and CMV-free survival at 100 days after HSCT. We compared the incidences of laboratory-defined adverse events (AEs) during treatment with ganciclovir and foscarnet. RESULTS: Among 969 children, the median (interquartile range) age was 6.5 (3.1-11.5) years, and 80% underwent allogeneic HSCT. Two hundred forty-four (25%) children developed CMV viremia. Older age (odds ratio [OR], 0.95; 95% CI, 0.92-0.98), male sex (OR, 0.71; 95% CI, 0.51-0.99), non-Black, non-White race (OR, 0.56; 95% CI, 0.36-0.87), umbilical cord blood donor source (OR, 0.28; 95% CI, 0.08-0.97), and CMV seropositivity (R-/D+: OR, 0.17; 95% CI, 0.07-0.41; R+/D-: OR, 0.14; 95% CI, 0.09-0.21; R+/D+: OR, 0.08; 95% CI, 0.04-0.15) were associated with lower odds of 100-day CMV-free survival. Compared with foscarnet, ganciclovir was associated with lower incidences of thrombocytopenia (incidence rate ratio [IRR], 0.38; 95% CI, 0.15-0.97), electrolyte AEs (IRR, 0.42; 95% CI, 0.24-0.75), endocrine AEs (IRR, 0.52; 95% CI, 0.34-0.79), and renal AEs (IRR, 0.36; 95% CI, 0.19-0.65). CONCLUSIONS: CMV viremia occurred commonly among children after HSCT, and ganciclovir and foscarnet were associated with distinct toxicity profiles among children with CMV infection. These findings should be considered when developing CMV prevention and treatment strategies for children after HSCT.
Authors
Heston, SM; Young, RR; Tanaka, JS; Jenkins, K; Vinesett, R; Saccoccio, FM; Martin, PL; Chao, NJ; Kelly, MS
MLA Citation
Heston, Sarah M., et al. “Risk Factors for CMV Viremia and Treatment-Associated Adverse Events Among Pediatric Hematopoietic Stem Cell Transplant Recipients.Open Forum Infect Dis, vol. 9, no. 2, Feb. 2022, p. ofab639. Pubmed, doi:10.1093/ofid/ofab639.
URI
https://scholars.duke.edu/individual/pub1509464
PMID
35111869
Source
pubmed
Published In
Open Forum Infectious Diseases
Volume
9
Published Date
Start Page
ofab639
DOI
10.1093/ofid/ofab639

Outcomes of pediatric patients with therapy-related myeloid neoplasms.

Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival. Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end-organ failure, as compared to only 20.9% of deaths in the reduced-intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD was associated with worse OS. In addition, a diagnosis of therapy-related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS. Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs.
Authors
Sharma, A; Huang, S; Li, Y; Brooke, RJ; Ahmed, I; Allewelt, HB; Amrolia, P; Bertaina, A; Bhatt, NS; Bierings, MB; Bies, J; Brisset, C; Brondon, JE; Dahlberg, A; Dalle, J-H; Eissa, H; Fahd, M; Gassas, A; Gloude, NJ; Goebel, WS; Goeckerman, ES; Harris, K; Ho, R; Hudspeth, MP; Huo, JS; Jacobsohn, D; Kasow, KA; Katsanis, E; Kaviany, S; Keating, AK; Kernan, NA; Ktena, YP; Lauhan, CR; López-Hernandez, G; Martin, PL; Myers, KC; Naik, S; Olaya-Vargas, A; Onishi, T; Radhi, M; Ramachandran, S; Ramos, K; Rangarajan, HG; Roehrs, PA; Sampson, ME; Shaw, PJ; Skiles, JL; Somers, K; Symons, HJ; de Tersant, M; Uber, AN; Versluys, B; Cheng, C; Triplett, BM
MLA Citation
Sharma, Akshay, et al. “Outcomes of pediatric patients with therapy-related myeloid neoplasms.Bone Marrow Transplant, vol. 56, no. 12, Dec. 2021, pp. 2997–3007. Pubmed, doi:10.1038/s41409-021-01448-x.
URI
https://scholars.duke.edu/individual/pub1496041
PMID
34480120
Source
pubmed
Published In
Bone Marrow Transplant
Volume
56
Published Date
Start Page
2997
End Page
3007
DOI
10.1038/s41409-021-01448-x

Parental limited English proficiency in pediatric stem cell transplantation: Clinical impact and health care utilization.

BACKGROUND: Limited English proficiency (LEP) is associated with adverse clinical outcomes. The clinical impact of LEP in hematopoietic stem cell transplant (HSCT) has not been studied. The objectives of this study were to compare HSCT outcomes and health care utilization of Hispanic pediatric patients with and without parental LEP. METHODS: We conducted a retrospective review of Hispanic/Latino pediatric patients receiving HSCT at a single institution. Families were identified as LEP or English proficient (EP) based on clinicians' notes, social work documentation, or the signature of a Spanish interpreter on treatment consents. RESULTS: A total of 83 Hispanic/Latino patients were identified with 53 (65.1%) having parental LEP. More patients in the LEP group had a documented financial burden at pretransplant psychosocial evaluation (72.2% vs. 41.4%, p = .009). LEP patients were more likely to have health insurance coverage through government-sponsored Medicaid (76.9% vs. 27.6%, p < .001). LEP patients were hospitalized on average 13 days longer than EP patients, and LEP patients were more likely to have pretransplant cytomegalovirus (CMV) reactivity (67.3%) than EP patients (p = .001). Overall survival was lower in LEP than EP, but was not statistically significant (p = .193). Multivariable Cox modeling suggested a potentially higher risk of death in LEP versus EP (hazard ratio = 1.56, 95% CI: 0.38, 6.23). CONCLUSIONS: Parental LEP in HSCT is associated with prolonged hospitalization and pretransplant CMV reactivity. These factors are associated with posttransplant complications and death. Our results suggest parental LEP is a risk factor for poor HSCT outcomes. Further study is warranted in a larger cohort.
MLA Citation
Robles, Joanna M., et al. “Parental limited English proficiency in pediatric stem cell transplantation: Clinical impact and health care utilization.Pediatr Blood Cancer, vol. 68, no. 9, Sept. 2021, p. e29174. Pubmed, doi:10.1002/pbc.29174.
URI
https://scholars.duke.edu/individual/pub1484724
PMID
34109732
Source
pubmed
Published In
Pediatr Blood Cancer
Volume
68
Published Date
Start Page
e29174
DOI
10.1002/pbc.29174

Anaerobic Antibiotics and the Risk of Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

<jats:p>Background: The gut microbiota interacts extensively with the host immune system and thus may modify the risk of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). During the post-transplant neutropenic period, the majority of allogeneic HSCT recipients receive empirical broad-spectrum antibiotics for febrile neutropenia. We hypothesized that receipt of an antibiotic regimen with an anaerobic spectrum of activity is associated with a higher risk of grade II-IV acute GVHD than receipt of a non-anaerobic antibiotic regimens.</jats:p> <jats:p>Methods: In this single-center retrospective cohort study, we evaluated associations between peri-transplant receipt of antibiotics with an anaerobic spectrum of activity and the risk and severity of GVHD among 877 adults who received an allogeneic HSCT between January 1, 2005 and December 31, 2016. We identified 609 patients who developed febrile neutropenia after HSCT and compared GVHD risk and mortality among patients who received anaerobic antibiotics (piperacillin-tazobactam or carbapenems; n=333) to patients who received only antibiotics with minimal activity against anaerobes (aztreonam, ceftazidime, or cefepime; n=276). Antibiotics received by patients between 7 days before and 28 days after allogeneic HSCT and GVHD diagnoses were verified via manual review of medication orders and provider notes in electronic medical records.</jats:p> <jats:p>Results: Receipt of anaerobic antibiotics was associated with an increased risks of grade II-IV acute GVHD (hazard ratio (HR): 1.41; 95% confidence interval (CI): 1.10-1.79; P=0.01) and acute GVHD mortality (HR: 1.87; 95% CI: 1.13, 3.11; P=0.02). This hazard was primarily associated with acute GVHD of the gut or liver (HR: 1.38; 95% CI: 1.06, 1.79; P=0.02). The association remained with even short (&lt;7 days) courses of anaerobic antibiotics. Anaerobic antibiotic exposure was not associated with acute skin GVHD (HR: 0.97; 95% CI: 0.69, 1.37; P=0.88), chronic GVHD diagnosis (HR: 0.93; 95% CI: 0.70, 1.23; P=0.43), or chronic GVHD mortality (HR: 0.89; 95% CI: 0.44, 1.81; P=0.76).</jats:p> <jats:p>Conclusions: Receipt of anaerobic antibiotics for febrile neutropenia post-HSCT is associated with an increased risks of acute GVHD of the gut or liver and acute GVHD mortality. Limiting use of antibiotics with an anaerobic spectrum of activity after allogeneic HSCT may reduce acute GVHD incidence and mortality.</jats:p> <jats:sec> <jats:title>Disclosures</jats:title> <jats:p>Sung: Novartis: Research Funding; Merck: Research Funding; Seres: Research Funding. Martin:Novartis Pharmaceuticals: Other: research support; Jazz Pharmaceuticals: Other: research support.</jats:p> </jats:sec>
Authors
Tanaka, J; Young, R; Spees, L; Jenkins, K; Sung, AD; Martin, PL; Heston, S; Thompson, JC; Seed, P; Arshad, M; Kelly, M
MLA Citation
Tanaka, John, et al. “Anaerobic Antibiotics and the Risk of Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.” Blood, vol. 134, no. Supplement_1, American Society of Hematology, 2019, pp. 1992–1992. Crossref, doi:10.1182/blood-2019-125080.
URI
https://scholars.duke.edu/individual/pub1469974
Source
crossref
Published In
Blood
Volume
134
Published Date
Start Page
1992
End Page
1992
DOI
10.1182/blood-2019-125080