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 thalassemia, 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.

Positions:

Professor of Pediatrics

Pediatrics, Blood and Marrow Transplantation
School of Medicine

Chief, Division of Pediatric Blood and Marrow Transplantation

Pediatrics, Blood and Marrow Transplantation
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, Blood and Marrow Transplantation
Awarded By
National Institutes of Health
Role
Investigator
Start Date
End Date

CART19 CTL019B2205J

Administered By
Pediatrics, Blood and Marrow Transplantation
Role
Principal Investigator
Start Date
End Date

Defibrotide Phase III Comparing Defibrotide vs Best Supportive Care

Administered By
Pediatrics, Blood and Marrow Transplantation
Role
Principal Investigator
Start Date
End Date

PBMTC SUP 1601 Pathogen Identification in Pediatric HSCT

Administered By
Pediatrics, Blood and Marrow Transplantation
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, Blood and Marrow Transplantation
Role
Principal Investigator
Start Date
End Date

Publications:

Results from an international phase 2 study of the anti-CD22 immunotoxin moxetumomab pasudotox in relapsed or refractory childhood B-lineage acute lymphoblastic leukemia.

BACKGROUND: In a multicenter phase 1 study of children with relapsed/refractory acute lymphoblastic leukemia (ALL), moxetumomab pasudotox, an anti-CD22 immunotoxin, demonstrated a manageable safety profile and preliminary evidence of clinical activity. A phase 2 study further evaluated efficacy. PROCEDURE: This international, multicenter, phase 2 study enrolled children with relapsed/refractory B-cell precursor ALL who received moxetumomab pasudotox 40 µg/kg intravenously every other day, for six doses per 21-day cycle. The primary objective was to evaluate the complete response (CR) rate. Secondary objectives included safety, pharmacokinetics, and immunogenicity evaluations. RESULTS: Thirty-two patients (median age, 10 years) were enrolled at 16 sites; 30 received study drug and were evaluable for safety; 28 were evaluable for response. The objective response rate was 28.6%, with three patients (10.7%) achieving morphologic CR, and five patients (17.9%) achieving partial response. Disease progression occurred in 11 patients (39.3%). Ten patients (33.3%) experienced at least one treatment-related serious adverse event, including capillary leak syndrome (CLS; n = 6), hemolytic uremic syndrome (HUS; n = 4), and treatment-related death (n = 1) from pulmonary edema. No differences were observed in inflammatory markers in patients who did or did not develop CLS or HUS. CONCLUSIONS: Despite a signal for clinical activity, this phase 2 study was terminated at interim analysis for a CR rate that did not reach the stage 1 target. Preclinical data suggest enhanced efficacy of moxetumomab pasudotox via continuous infusion or in combination regimens; thus, further studies designed to optimize the efficacy and safety of moxetumomab pasudotox in pediatric ALL may be warranted.
Authors
Shah, NN; Bhojwani, D; August, K; Baruchel, A; Bertrand, Y; Boklan, J; Dalla-Pozza, L; Dennis, R; Hijiya, N; Locatelli, F; Martin, PL; Mechinaud, F; Moppett, J; Rheingold, SR; Schmitt, C; Trippett, TM; Liang, M; Balic, K; Li, X; Vainshtein, I; Yao, NS; Pastan, I; Wayne, AS
MLA Citation
Shah, Nirali N., et al. “Results from an international phase 2 study of the anti-CD22 immunotoxin moxetumomab pasudotox in relapsed or refractory childhood B-lineage acute lymphoblastic leukemia.Pediatr Blood Cancer, vol. 67, no. 5, May 2020, p. e28112. Pubmed, doi:10.1002/pbc.28112.
URI
https://scholars.duke.edu/individual/pub1428019
PMID
31944549
Source
pubmed
Published In
Pediatr Blood Cancer
Volume
67
Published Date
Start Page
e28112
DOI
10.1002/pbc.28112

Microbiology and Risk Factors for Hospital-Associated Bloodstream Infections Among Pediatric Hematopoietic Stem Cell Transplant Recipients.

Background: Children undergoing hematopoietic stem cell transplantation (HSCT) are at high risk for hospital-associated bloodstream infections (HA-BSIs). This study aimed to describe the incidence, microbiology, and risk factors for HA-BSI in pediatric HSCT recipients. Methods: We performed a single-center retrospective cohort study of children and adolescents (<18 years of age) who underwent HSCT over a 20-year period (1997-2016). We determined the incidence and case fatality rate of HA-BSI by causative organism. We used multivariable Poisson regression to identify risk factors for HA-BSI. Results: Of 1294 patients, the majority (86%) received an allogeneic HSCT, most commonly with umbilical cord blood (63%). During the initial HSCT hospitalization, 334 HA-BSIs occurred among 261 (20%) patients. These were classified as gram-positive bacterial (46%), gram-negative bacterial (24%), fungal (12%), mycobacterial (<1%), or polymicrobial (19%). During the study period, there was a decline in the cumulative incidence of HA-BSI (P = .021) and, specifically, fungal HA-BSIs (P = .002). In multivariable analyses, older age (incidence rate ratio [IRR], 1.03; 95% confidence interval [CI], 1.01-1.06), umbilical cord blood donor source (vs bone marrow; IRR, 1.69; 95% CI, 1.19-2.40), and nonmyeloablative conditioning (vs myeloablative; IRR, 1.85; 95% CI, 1.21-2.82) were associated with a higher risk of HA-BSIs. The case fatality rate was higher for fungal HA-BSI than other HA-BSI categories (21% vs 6%; P = .002). Conclusions: Over the past 2 decades, the incidence of HA-BSIs has declined among pediatric HSCT recipients at our institution. Older age, umbilical cord blood donor source, and nonmyeloablative conditioning regimens are independent risk factors for HA-BSI among children undergoing HSCT.
Authors
Akinboyo, IC; Young, RR; Spees, LP; Heston, SM; Smith, MJ; Chang, Y-C; McGill, LE; Martin, PL; Jenkins, K; Lugo, DJ; Hazen, KC; Seed, PC; Kelly, MS
MLA Citation
Akinboyo, Ibukunoluwa C., et al. “Microbiology and Risk Factors for Hospital-Associated Bloodstream Infections Among Pediatric Hematopoietic Stem Cell Transplant Recipients.Open Forum Infect Dis, vol. 7, no. 4, Apr. 2020, p. ofaa093. Pubmed, doi:10.1093/ofid/ofaa093.
URI
https://scholars.duke.edu/individual/pub1436609
PMID
32284949
Source
pubmed
Published In
Open Forum Infectious Diseases
Volume
7
Published Date
Start Page
ofaa093
DOI
10.1093/ofid/ofaa093

The Effect of Limited-English Proficiency on Hematopoietic Stem Cell Transplantation Outcomes: A Retrospective Cohort Study of Hispanic Pediatric Transplant Patients at a Single Institution.

Authors
Robles, JM; Troy, JD; Schroeder, KM; Martin, PL; LeBlanc, TW
MLA Citation
Robles, Joanna M., et al. “The Effect of Limited-English Proficiency on Hematopoietic Stem Cell Transplantation Outcomes: A Retrospective Cohort Study of Hispanic Pediatric Transplant Patients at a Single Institution.Biology of Blood and Marrow Transplantation, vol. 26, no. 3, ELSEVIER SCIENCE INC, 2020, pp. S195–96.
URI
https://scholars.duke.edu/individual/pub1434758
Source
wos
Published In
Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
Volume
26
Published Date
Start Page
S195
End Page
S196

Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children's Oncology Group Studies P9904 and P9905.

The delayed intensification (DI) enhanced outcome for patients with acute lymphoblastic leukemia (ALL) treated on BFM 76/79 and CCG 105 after a prednisone-based induction. Childrens Oncology Group protocols P9904/9905 evaluated DI via a post-induction randomization for eligible National Cancer Institute (NCI) standard (SR) and high-risk (HR) patients. A second randomization compared intravenous methotrexate (IV MTX) as a 24- (1 g/m2) vs. 4-h (2 g/m2) infusion. NCI SR patients received a dexamethasone-based three-drug and NCI HR/CNS 3 SR patients a prednisone-based four-drug induction. End induction MRD (minimal residual disease) was obtained but did not impact treatment. DI improved the 10-year continuous complete remission (CCR) rate; 75.5 ± 2.5% vs. 81.8 ± 2.2% p = 0.002, whereas MTX administration did not; 4-h 80.8 ± 1.9%; 24-h 81.4 ± 1.9% (p = 0.7780). Overall survival (OS) at 10 years did not differ with DI: 91.4 ± 1.6% vs. 90.9 ± 1.7% (p = 0.25) without but was higher with the 24-h MTX infusion; 4-h 91.1 ± 1.4%; 24-h 93.9 ± 1.2% (p = 0.0209). MRD predicted outcome; 10-year CCR 87.7 ± 2.2 and 82.1 ± 2.5% when MRD was <0.01% with/without DI (p = 0.007) and 54.3 ± 8% and 44 ± 8% for patients with MRD ≥ 0.01% with/without DI (p = 0.11). DI improved CCR for patients with B-ALL with and without end induction MRD.
Authors
Winick, N; Martin, PL; Devidas, M; Shuster, J; Borowitz, MJ; Paul Bowman, W; Larsen, E; Pullen, J; Carroll, A; Willman, C; Hunger, SP; Carroll, WL; Camitta, BM
MLA Citation
Winick, Naomi, et al. “Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children's Oncology Group Studies P9904 and P9905.Leukemia, vol. 34, no. 4, Apr. 2020, pp. 1006–16. Pubmed, doi:10.1038/s41375-019-0642-2.
URI
https://scholars.duke.edu/individual/pub1421698
PMID
31728054
Source
pubmed
Published In
Leukemia
Volume
34
Published Date
Start Page
1006
End Page
1016
DOI
10.1038/s41375-019-0642-2

Gut Colonization Preceding Mucosal Barrier Injury Bloodstream Infection in Pediatric Hematopoietic Stem Cell Transplantation Recipients.

The gastrointestinal tract is the predicted reservoir for most bloodstream infections (BSIs) after hematopoietic stem cell transplantation (HSCT). Whole-genome sequencing and comparative genomics have the potential to improve our understanding of the dynamics of gut colonization that precede BSI in HSCT recipients. Within a prospective cohort study of children (age <18 years) undergoing HSCT, 9 subjects met criteria for mucosal barrier injury BSI. We performed whole-genome sequencing of the blood culture isolate and weekly fecal samples preceding the BSI to compare the genetic similarity of BSI isolates to fecal strains. We evaluated temporal associations between antibiotic exposures and the abundances of BSI strains in the gut microbiota and correlated the detection of antibiotic resistance genes with the phenotypic antibiotic resistance of these strains. The median patient age was 2.6 years, and 78% were male. BSIs were caused by Escherichia coli (n = 5), Enterococcus faecium (n = 2), Enterobacter cloacae (n = 1), and Rothia mucilaginosa (n = 1). In the 6 BSI episodes with evaluable comparative genomics, the fecal strains were identical to the blood culture isolate (>99.99% genetic similarity). Gut domination by these strains preceded only 4 of 7 E. coli or E. faecium BSIs by a median of 17 days (range, 6 to 21 days). Increasing abundances of the resulting BSI strains in the gut microbiota were frequently associated with specific antibiotic exposures. E. cloacae and R. mucilaginosa were not highly abundant in fecal samples preceding BSIs caused by these species. The detection of antibiotic resistance genes for β-lactam antibiotics and vancomycin predicted phenotypic resistance in BSI strains. Bacterial strains causing mucosal barrier injury BSI in pediatric HSCT recipients were observed in the gut microbiota before BSI onset, and changes in the abundances of these strains within the gut preceded most BSI episodes. However, frequent sampling of the gut microbiota and sampling of other ecological niches is likely necessary to effectively predict BSI in HSCT recipients.
Authors
Kelly, MS; Ward, DV; Severyn, CJ; Arshad, M; Heston, SM; Jenkins, K; Martin, PL; McGill, L; Stokhuyzen, A; Bhattarai, SK; Bucci, V; Seed, PC
MLA Citation
Kelly, Matthew S., et al. “Gut Colonization Preceding Mucosal Barrier Injury Bloodstream Infection in Pediatric Hematopoietic Stem Cell Transplantation Recipients.Biol Blood Marrow Transplant, vol. 25, no. 11, Nov. 2019, pp. 2274–80. Pubmed, doi:10.1016/j.bbmt.2019.07.019.
URI
https://scholars.duke.edu/individual/pub1397931
PMID
31326608
Source
pubmed
Published In
Biol Blood Marrow Transplant
Volume
25
Published Date
Start Page
2274
End Page
2280
DOI
10.1016/j.bbmt.2019.07.019