Gender Differences in Pediatric Hematopoietic Stem Cell Transplantation (HSCT)

Pilot Study on Gender Differences in Hematopoietic Cell Transplantation Outcomes in the Pediatric Population

Gender medicine considers the way in which gender, male or female, affects the development and impact of diseases and the response to therapies. It can be said that it is a new transversal dimension of medicine, which evaluates the gender differences in the physiology, pathophysiology and clinic of many diseases and thus sets itself the goal of reaching optimal therapeutic decisions both in men and women based on proven scientific evidence.

Although knowledge of gender medicine has increased significantly in recent years, a gender approach has not been much developed in pediatrics. In the field of bone marrow transplants, hematopoietic stem cell transplantation is known to be the most effective consolidation therapy in some high-risk hematology malignancies such as acute lymphoblastic leukemia and acute myeloid leukemia, and represents one of the potential treatment for patients suffering from solid tumors and genetic hematological, metabolic diseases and primary immunodeficiencies. Huge progress has been made in high resolution donor typing, choice of conditioning regimens, manipulation of hematopoietic stem cells (HSC) and prevention of serious infections in recent years, which have significantly improved the survival rate of patients undergoing to this procedure.

International literature regarding the response and outcomes from hematopoietic cell transplantation in a gender perspective is completely absent, for these reasons this pilot study was born from the need to understand from a broader perspective and in order to better understand how the gender may or not influence the outcome of transplantation in pediatric patients.

This retrospective analysis of the data will concern all patients who underwent allogeneic or autologous bone marrow transplant. The data will be collected from clinical records and from Regional electronic databases. All data will be collected anonymously and an identification code will be assigned to each case.

Study Overview

• Status: Completed
• Conditions: Hematopoietic Stem Cell Transplantation
• Intervention / Treatment: Procedure: Hematopoietic stem cell transplantation

• Study Type: Observational
• Enrollment (Actual): 200

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Population of pediatric patients undergoing hematopoietic stem cell transplantation

Description

Inclusion Criteria:

1. Patients aged between 4 months and 17 years
2. Diagnosis of oncohaematological disease subjected to hematopoietic stem cell transplantation
3. Allogeneic or autologous bone marrow transplantation from January 2000 to October 2018
4. Consent acquired for the processing of data for research purposes

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Female group; Pediatric female patients undergoing hematopoietic stem cell transplantation	Procedure: Hematopoietic stem cell transplantation; Allogeneic or autologous bone marrow transplant
Male group; Pediatric male patients undergoing hematopoietic stem cell transplantation	Procedure: Hematopoietic stem cell transplantation; Allogeneic or autologous bone marrow transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gender-related difference in overall 12-month toxicity	Differences in toxicity (hepatic, renal, pulmonary, gastrointestinal) in males and females recipients	12 months after transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gender difference in overall survival (OS)	Overall survival comparison from males and females recipients	12 months after transplant
Gender difference in post-transplant primary disease recurrence	Incidence of post-transplant leukemic relapse in males and females recipients	12 months after transplant
Gender difference in the frequency of transplant-related toxicity at 12 months	Frequency of post-transplant liver, kidney, pulmonary, gastrointestinal, endocrine, cardiac toxicity	12 months after transplant
Gender difference in infectious complications	Number of episodes of sepsis / fungal infections / viral reactivations after HSCT	12 months after transplant
Gender difference in the frequency of adverse events due to pre-transplant conditioning regimen	Number of chemo- radiotherapy-related adverse events. Toxicity was graded according to National Cancer Institute (NCI) common toxicity criteria	12 months after transplant
Gender difference in severity of adverse events due to pre-transplant conditioning regimen	Severity of chemo- radiotherapy-related adverse events. Toxicity wil be graded according to National Cancer Institute (NCI) common toxicity criteria	12 months after transplant
Gender difference in timing of hematological engraftment	Engraftment defined as the engraftment of polymorphonuclear neutrophils (PMN) on the first day of 3 consecutive days with PMN number greater than 500 / ml3 and engraftment of platelets defined as number of platelets> 20,000 / ml3 in the absence of platelet transfusion in the previous 5 days.	12 months after transplant
Gender difference in frequency of primary graft failure	Engraftment defined as the engraftment of polymorphonuclear neutrophils (PMN) on the first day of 3 consecutive days with PMN number greater than 500 / ml3 and engraftment of platelets defined as number of platelets> 20,000 / ml3 in the absence of platelet transfusion in the previous 5 days. Primary graft failure is defined as no evidence of engraftment or hematological recovery of donor cells, within the first month after transplant, without evidence of disease relapse.	12 months after transplant
Gender difference in frequency of secondary graft failure	Engraftment defined as the engraftment of polymorphonuclear neutrophils (PMN) on the first day of 3 consecutive days with PMN number greater than 500 / ml3 and engraftment of platelets defined as number of platelets> 20,000 / ml3 in the absence of platelet transfusion in the previous 5 days. Secondary graft failure refers to the loss of a previously functioning graft, resulting in cytopenia involving at least two blood cell lineages.	12 months after transplant

Collaborators and Investigators

• Sponsor: IRCCS Burlo Garofolo
• Investigators: Study Director: Alessandra Maestro, PharmD, PhD, Institute for Maternal and Child Health IRCCS Burlo Garofolo; Principal Investigator: Natalia Maximova, MD, Institute for Maternal and Child Health IRCCS Burlo Garofolo

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2000
• Primary Completion (ACTUAL): October 1, 2018
• Study Completion (ACTUAL): October 1, 2019

Study Registration Dates

• First Submitted: October 2, 2020
• First Submitted That Met QC Criteria: October 2, 2020
• First Posted (ACTUAL): October 8, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 2, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: gender, pediatrics, hematopoietic cell transplantation
• Other Study ID Numbers: RC 25/2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No