Methodology for the Start-up of a Pediatric Hematopoietic Stem Cell Transplant Unit (pHSCTU) in Middle-Income Countries (MICs): An Exportable Model?
Authors: Verna Marta , Rovelli Attilio , Conter Valentino , Canesi Marta , Majolino Ignazio , Othman Dosti , Faeq Vian , Noguera Jabibi , Benitez Maria Liz , Dastan Othman , Biondi Andrea 
Published: November 2019

Introduction: Blood or marrow transplantation (BMT) programs are largely insufficient to meet the growing need in MICs. Where BMT is not available families, charities or governments often seek for alternative programs, usually to send children abroad for BMT; this policy is associated with many drawbacks, including costs, and difficulties to manage transplant related complications after the patient return home. Evaluation of feasibility and sustainability plays a crucial role in the success of all cooperative projects but especially of high specialization ones.

Materials and methods: In 2016 the first HSCTU inclusive of a pediatric section was developed in Iraqi Kurdistan at Hiwa Cancer Hospital of Sulaymaniah, thanks to a cooperative project funded by the Italian Agency for Development Cooperation and to the availability of professionals from specialized centers to train local personnel. After verifying with an appropriate grid that essential requirements were in place, a capacity building project was started. An intensive educational course was carried on initially and then, using a training on the job approach, all specific skills were set-up and/or implemented. A complete protocol handbook was created with involvement of the local staff; a staggered approach to the disease was chosen, starting from low risk diseases and moving later to high risk ones. After 3 years project the center is now completely autonomous; up to now they have been performed 158 transplants (autologous and allogeneic, both in adult and children) with results comparable with those of high-income countries (HICs). In a cohort of 26 pediatric patients with thalassemia the event free survival (EFS) is over 90% with a median follow up of 492 days.

Next to this experience, in 2018 a new project has been activated in Paraguay, following a specific request from the pediatric hospital Ninos de Acosta Nu in Asuncion. The similar methodology has been applied. After documenting the feasibility, a 3 years project has been set-up, with an initial intensive educational course, followed by training on the job by experts in the field and also limited training of the local staff abroad. A six months continuously oversight by experienced nurses and periodically by expert physicians has been planned along with the continuous support through on line contacts; focused training in Europe on minimal residual disease, chimerism, apheresis and HLA typing has been scheduled. The first allogeneic transplant from matched sibling donor is planned in autumn 2019.

Discussion: Based on our experience new centers should start with patients highly curable, low-risk matched sibling transplants, well-established context-appropriate protocols with minimal toxicity, proven high success rates and contained costs. If socio-economical context of the country and needs of the population allow to move to oncological patients, a staggered approach is suggested: from matched sibling donor transplant to mismatched ones. Minimal essential requirements for a pediatric BMT start-up activity may be affordable in many MICs, if health authorities and/or local charities/foundations are committed. This shall include good quality blood products (leuco-reduced or irradiated); drugs for conditioning regimens (busulphan, tiothepa, fludarabine, cyclophosphamide, melphalan), GVHD prophylaxis and treatment (methotrexate, thymoglobuline, cyclosporine, mycophenolate mofetil), infections control (broad spectrum antibiotics, one anti-mold drug, ganciclovir) and essential laboratory tests (at least cyclosporin levels and citomegalovirus copies count).

Conclusion: The strategy described above requires the availability of expert BMT physicians and nurses willing to rotate periodically in MICs Units for training on the job and supervision. This model is replicable in different contexts, allows a fast development of BMT units in MICs, and in our opinion compares favorably with that of offering training to multiple professionals in specialized centers.

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Disclosures

No relevant conflicts of interest to declare.