Paeds · haematology-oncology-and-transfusion
Haematopoietic stem-cell transplantation
Also known as Bone marrow transplant · HSCT · Allogeneic stem-cell transplant · Autologous stem-cell transplant · Graft-versus-host disease · Sinusoidal obstruction syndrome
Fellowship guide to haematopoietic stem-cell transplantation in children. Covers the separation of autologous from allogeneic transplant, the donor hierarchy from the matched sibling through the matched unrelated and the haploidentical to the cord blood unit, the graft-versus-leukaemia effect and the graft-versus-host disease it produces, the myeloablative and reduced-intensity conditioning, the acute and chronic graft-versus-host disease and its prophylaxis with calcineurin inhibitors and post-transplantation cyclophosphamide, the hepatic sinusoidal obstruction syndrome and its treatment with defibrotide, the neutrophil and platelet engraftment milestones, the graft failure and the donor chimerism, and the supportive care of the febrile neutropenia and the opportunistic infection.
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Target exams
Red flags
- A diarrhoeal rash with rising bilirubin in the first hundred days after an allogeneic transplant is acute graft-versus-host disease until proven otherwise and is biopsied, not assumed
- Weight gain, a tender liver and jaundice within three weeks of conditioning is the sinusoidal obstruction syndrome; delay in starting defibrotide in the severe form is fatal
- A fever in a child with a neutrophil count under zero point five times ten to the nine per litre after a transplant is febrile neutropenia; the antipseudomonal beta-lactam goes in within one hour after blood cultures
- Failure of the neutrophil count to reach zero point five times ten to the nine per litre by day twenty-eight is primary graft failure and demands an urgent donor chimerism and a search for rejection
- Pneumocystis prophylaxis, viral reactivation surveillance and irradiated blood products continue for months after the transplant; a single non-irradiated unit can cause the fatal transfusion-associated graft-versus-host disease
- Post-transplantation cyclophosphamide is given on days three and four, not at the bedside later; the timing is what removes the alloreactive T-cells and delivers the graft-versus-host prophylaxis
Life stages
Care settings
Clinical exam formats
Board mappings
- Names the autologous and the allogeneic stem-cell transplant and the matched sibling donor as the preferred allogeneic source
- Recognises graft-versus-host disease as the defining complication of the allogeneic transplant and the need for prophylaxis
- States the neutrophil engraftment milestone of zero point five times ten to the nine per litre for three consecutive days
- Explains the graft-versus-leukaemia effect and the trade-off against the graft-versus-host disease that shapes the donor and the intensity choice
- Coordinates the donor hierarchy from the matched sibling through the matched unrelated and haploidentical to the cord blood, with the HLA matching that governs it
- Distinguishes the myeloablative from the reduced-intensity conditioning and applies each to the child's disease and comorbidity
- Acute graft-versus-host disease prophylaxis uses a calcineurin inhibitor with methotrexate or post-transplantation cyclophosphamide, not a glucocorticoid alone
- The sinusoidal obstruction syndrome is treated with defibrotide at twenty-five milligrams per kilogram per day in four divided doses, started early
- Febrile neutropenia after a transplant gets the antipseudomonal beta-lactam within one hour after the blood cultures, with the empiric escalation for the unstable child
- Counsels the family on the intent of the transplant, the conditioning toxicity, the engraftment period and the long-term complications including infertility and second malignancy
- Builds the multidisciplinary plan linking the transplant centre, the infectious diseases, the family and the primary care for the long immunosuppression
- Synthesises the long-case child after a transplant into a graft-versus-host, infectious and late-effects plan
- Level 1: Recognition of the indications for the transplant and the common early complications of mucositis, fever and rash
- Level 2: Application of the donor selection, the conditioning and the engraftment milestones to the plan
- Level 3: Coordination of the graft-versus-host prophylaxis, the opportunistic prophylaxis and the long-term survivorship
- The classification of the transplant into autologous and allogeneic and the donor hierarchy
- The acute and chronic graft-versus-host disease, the staging and the prophylaxis
- The sinusoidal obstruction syndrome, the criteria and the defibrotide treatment
- Structured assessment of the post-transplant child for the rash, the diarrhoea, the jaundice and the fever
- Communication of the risks and the long course of the transplant to the child and the family
- Recognition of the transplant emergencies of the severe graft-versus-host disease, the sinusoidal obstruction syndrome and the febrile neutropenia
- The transplant as the curative intent for the high-risk leukaemia, the marrow failure and the immunodeficiency
- The graft-versus-leukaemia effect and the donor lymphocyte as the immunological basis of the allogeneic cure
- The supportive care of the immunocompromised child through the engraftment period
- Recognition of the indications for the paediatric stem-cell transplant and the donor sources
- Application of the prophylaxis for the graft-versus-host disease and the opportunistic infection
- Coordination of the long-term surveillance for the growth, the endocrine and the late effects
- Canadian approach to the donor selection and the HLA matching in the paediatric transplant
- The conditioning intensity and the graft-versus-host prophylaxis as the determinants of the outcome
- The contemporary supportive care and the late-effects surveillance
Overview & Definition
A child relapses with leukaemia, or is born with a faulty haemoglobin, or fails to make any white cells at all, and the question becomes whether to replace the entire blood-forming system. That replacement is the haematopoietic stem-cell transplantation, and it sits at the most intensive end of paediatric medicine. The candidate who can hold the intent of the procedure, donor choice, conditioning and the complications together has the framework that organises a large block of the fellowship syllabus, because the transplant pulls in oncology, immunology, hepatology and infectious disease at the same time. The acuity is high, the course is long, and the complications are the everyday reality of the transplant ward. [1]
Haematopoietic stem-cell transplantation is the infusion of haematopoietic stem cells after conditioning chemotherapy, with or without radiation, to rescue the marrow and, in the allogeneic form, to confer a new immune system with a graft-versus-leukaemia effect. The procedure is split into the autologous transplant, in which the child's own cells are collected and reinfused, and the allogeneic transplant, in which the cells come from a donor. The autologous form is a rescue that allows the high-dose chemotherapy, while the allogeneic form is an immune replacement that carries the graft-versus-leukaemia benefit and the graft-versus-host disease. The single most important distinction the candidate holds is between these two, because every decision that follows, the donor search, conditioning, prophylaxis and the complications, flows from it. [1][5]
The allogeneic transplant dominates this topic because it generates the complications that the exam tests. The donor is the organising variable, and the search moves from the matched sibling donor, the preferred source, through the matched unrelated donor, the haploidentical family donor and the umbilical cord blood unit, each with its own matching requirement, cell dose and risk profile. The graft-versus-leukaemia effect is the immunological prize of the allogeneic transplant, and the graft-versus-host disease is its price, and the modern practice is a constant negotiation between the two. The conditioning, whether myeloablative or reduced-intensity, determines the toxicity, the engraftment speed and the risk of the hepatic sinusoidal obstruction syndrome. [2][3]
The survival after a paediatric transplant depends on the disease, donor, conditioning and the complications, and the contemporary outcomes range from over ninety percent for the matched sibling transplant of a benign disease to under forty percent for the refractory leukaemia with the severe graft-versus-host disease. The candidate who carries these numbers, alongside the recognition of the transplant emergencies, holds reasoning boards reward. The rash, the diarrhoea, the jaundice and the fever in the post-transplant child are never dismissed, because each maps to a complication that demands a specific response. [1][12]
References12ShowHide
- [1]Kanate AS, Majhail NS, Savani BN Indications for Hematopoietic Cell Transplantation and Immune Effector Cell Therapy: Guidelines from the American Society for Transplantation and Cellular Therapy Biol Blood Marrow Transplant, 2020.PMID 32165328
- [2]Mangum DS, Caywood E A clinician's guide to HLA matching in allogeneic hematopoietic stem cell transplant Hum Immunol, 2022.PMID 35346535
- [3]Alsultan A, Abujoub R, Elbashir E The effect of intensity of conditioning regimen on the outcome of HSCT in children with sickle cell disease Clin Transplant, 2022.PMID 35929611
- [4]Bolaños-Meade J, Hamadani M, Wu J Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis N Engl J Med, 2023.PMID 37342922
- [5]Zeiser R, Blazar BR Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy N Engl J Med, 2017.PMID 29171820
- [6]Jagasia MH, Greinix HT, Arora M National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report Biol Blood Marrow Transplant, 2015.PMID 25529383
- [7]Zeiser R, Polverelli N, Ram R, et al. Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease N Engl J Med, 2021.PMID 34260836
- [8]Mohty M, Malard F, Alaskar AS Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a refined classification from the European Society for Blood and Marrow Transplantation Bone Marrow Transplant, 2023.PMID 37095231
- [9]Larue M, Malard F, Alaskar AS Management of liver sinusoidal obstruction syndrome/veno-occlusive disease in adults: a 2025 perspective from an international expert group Bone Marrow Transplant, 2025.PMID 40263636
- [10]Aziz MT, Kakadiya PP, Kush SM Defibrotide: An Oligonucleotide for Sinusoidal Obstruction Syndrome Ann Pharmacother, 2018.PMID 28914546
- [11]Kharfan-Dabaja MA, Kumar A, Ayala E, et al. Standardizing Definitions of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, and Donor Chimerism in Allogeneic Hematopoietic Cell Transplantation Transplant Cell Ther, 2021.PMID 34304802
- [12]Lehrnbecher T, Robinson P, Fisher B Guideline for the Management of Fever and Neutropenia in Children With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update J Clin Oncol, 2017.PMID 28459614