A bone marrow transplant from a matched brother or sister cures thalassemia major in most children, ending monthly transfusions and daily iron chelation. Results are best before 14 years of age and before iron damages the liver. This guide covers candidates, donors, preparation, the first 100 days, gene therapy, results and the stay.
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Pediatric Hematology and Oncology
A stem cell transplant from a matched brother or sister ends thalassemia major for good, freeing a child from monthly transfusions and iron chelation. Results are best when the transplant is done young, before iron has damaged the liver.
In thalassemia major, an inherited condition, the body cannot make enough normal hemoglobin. Children need blood transfusions every three to four weeks for life, and the iron from that blood builds up in the liver, heart and glands unless medicines remove it every day. A bone marrow transplant replaces the faulty blood-forming cells with healthy ones from a donor, and the child then makes normal blood. In the European registry of 1,493 patients, 91 percent of those transplanted from a tissue-matched sibling survived, and 83 percent were also free of thalassemia. Send us your child's diagnosis, transfusion and chelation history, ferritin and liver MRI results, and the tissue types of brothers and sisters if tested, and the pediatric transplant team will tell you whether a transplant fits and when.
91%
Survival after a matched sibling transplant, 1,493 patients, European registry
90 to 96%
Survival when the transplant came before 14 years of age
3 to 4 months
In Istanbul for most families
Free
Pediatric transplant team's review of your child's file
Transfusions keep children alive. A transplant can make them unnecessary.
Current experience world-wide is that more than 90% of patients now survive hematopoietic stem cell transplantation and disease-free survival is around 80%.
International expert panel of the European Society for Blood and Marrow Transplantation, Haematologica, 2014
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Three paths for a child with thalassemia major
Path
What it involves
What it offers
Transfusion and chelation
Blood every three to four weeks and daily iron-removing medicine, for life
Good survival with excellent care, but a lifelong burden and organ damage if chelation slips
Allogeneic stem cell transplant
High-dose preparation, then healthy cells from a donor, usually a matched sibling
A cure in most children, with risks from the transplant itself
Gene therapy
The child's own stem cells, corrected in the laboratory and returned
Transfusion independence in most patients treated in trials, available in few centers
Why age and the liver matter
Iron works against a good transplant. Every unit of blood carries iron that the body cannot excrete, and over the years it settles in the liver, causing enlargement and scarring. The surgeons and hematologists of Pesaro in Italy, who pioneered thalassemia transplants, showed in 1990 that this liver damage, more than any other factor, decided how children fared.
For patients under 16 years of age, transplantation of bone marrow from an HLA-identical donor offers a high probability of complication-free survival, particularly if they do not have hepatomegaly or portal fibrosis.
Pesaro series of 222 children, New England Journal of Medicine, 1990
An enlarged liver, more than two centimeters below the rib margin.
Portal fibrosis, scarring of the liver seen on biopsy.
A history of irregular or inadequate iron chelation.
Children with none of these factors fall into Pesaro class 1, those with one or two into class 2, and those with all three into class 3. The class remains a guide to risk in every transplant center today, and good chelation in the years before transplant is the single best way to keep a child in class 1.
Allogeneic HSCT for thalassemia is a curative approach that is employed internationally and produces excellent results.
European registry of 1,493 patients, Bone Marrow Transplantation, 2016
Which children are candidates?
The best time
Earlier wins.
The European Society for Blood and Marrow Transplantation registry collected 1,493 consecutive thalassemia transplants performed between 2000 and 2010, nine in ten of them in children. Children transplanted before 14 did best, with survival of 90 to 96 percent and thalassemia-free survival of 83 to 93 percent. Older patients still benefit, but their risk rises with the years of iron load behind them.
Preparing the child
In the months before transplant, the team intensifies chelation to bring iron down, in many children combining two drugs, and keeps hemoglobin above the usual threshold with regular transfusions to quiet the child's own overactive marrow, which by then has spent years expanding inside the bones and will fight hard against donor cells unless it is calmed first. Rejection and liver complications both become less likely.
Ferritin, liver iron measured by MRI and heart iron by cardiac T2-star MRI.
Organ checks.
Tissue typing of the child and of every brother and sister, and of the parents.
A liver biopsy in some children, when MRI and blood tests leave the degree of scarring unclear.
How does the transplant work?
A matched sibling is the starting point
Each full brother or sister has a one in four chance of sharing the child's tissue type. A sibling who carries thalassemia trait, and is therefore healthy, can donate safely. The European registry found the best results with these donors, and they remain the first choice everywhere.
1
Assessment
Two weeks of tests for the child and the donor, a central line, and fertility counseling before treatment begins.
2
Conditioning
Seven to ten days of chemotherapy, with busulfan or treosulfan combined with thiotepa, fludarabine and antibody treatment, chosen to clear the marrow and prevent rejection.
3
Day zero
The donor's marrow, collected that morning under anesthesia from the hip bones, goes in through the central line like a transfusion.
Why thalassemia needs strong preparation
Children with thalassemia have a marrow that has worked overtime for years to make more blood, and a strong immune system that has met many transfusions. Both push back against donor cells. Too light a conditioning lets the child's own marrow return, and thalassemia comes back with it. Doctors call this graft rejection. The preparation therefore aims for complete replacement, and blood tests in the weeks after transplant measure how much of the marrow comes from the donor.
Graft-versus-host disease, in which donor immune cells attack the child's skin, gut or liver, is the other main risk. Matched sibling donors, bone marrow rather than blood stem cells, and preventive medicines keep it uncommon in children.
Bone marrow or cord blood
A newborn sibling who matches offers another source, since the family can store the cord blood collected at birth. An international study of 485 children with thalassemia or sickle cell disease compared cord blood and bone marrow from matched siblings. Six years later, 97 percent of cord blood recipients and 95 percent of marrow recipients were alive. Cord blood recipients recovered their counts more slowly, had less acute graft-versus-host disease and none had extensive chronic disease.
Patients with TM or SCD have excellent outcomes after both HLA-identical sibling CBT and BMT.
Study of 485 patients, Blood, 2013
Transplantation from a human leukocyte Ag-identical sibling offered the best results, with OS and EFS of 91 ± 1% and 83 ± 1%, respectively.
European registry, Bone Marrow Transplantation, 2016
Full brothers and sisters, including a baby sibling whose cord blood can be saved.
A matched unrelated volunteer found through the international registries, an option that experienced centers now use with results approaching those of sibling transplants.
A half-matched parent, in selected cases.
When no sibling matches
Most children have no matched sibling. A search of international registries for an unrelated donor starts at once.
The team then discusses gene therapy and half-matched transplants honestly, including where each is available and how far the evidence has come.
The first 100 days
From day zero to home
1
Weeks one to four
Low counts in a protected single room with filtered air, transfusions, antibiotics, mouth care and nutrition support. A parent stays throughout.
2
Weeks four to eight
Donor cells take over and counts recover. The child moves to an apartment near the hospital and comes in several times a week.
3
Up to day 100
Medicines against graft-versus-host disease are tapered, donor cell levels are checked, and transfusions stop for good.
Days, cost and the trip
Plan three to four months. Tests for the child and the sibling donor take two weeks, conditioning a little over a week, and most families fly home around day 100, once counts are stable without transfusions and the child eats and takes medicines by mouth.
Cost depends on the donor, the preparation, the weeks in hospital and the medicines afterward, and the coordinator sets it out once the team has reviewed the file. The donor sibling's own tests and marrow collection are part of the plan.
One coordinator arranges the visa invitation letter for the family and the donor sibling, transfers and a furnished apartment near the hospital. Play specialists and teachers keep both children busy. Staff speak seven languages, and halal meals and a prayer room are available. Back home, the transplant physicians review blood counts and donor cell results sent by your local hematologist and stay reachable on the same WhatsApp number.
Signs that need the team at once
A temperature of 38 degrees or more, a new rash, diarrhea, yellow eyes, or a drop in hemoglobin that needs transfusion after the first weeks. The last can mean the graft is failing and needs tests the same day.
What about gene therapy?
Using the child's own cells
Gene therapy collects the child's own stem cells, adds a working beta-globin gene in the laboratory and returns them after busulfan conditioning. Using the child's own cells removes the donor search and the risk of graft-versus-host disease. In a phase 3 trial of 23 adults and children whose genotype was not beta-zero over beta-zero, 20 of 22 who could be evaluated stopped transfusions, including 6 of 7 under twelve, with an average hemoglobin of 11.7 grams per deciliter.
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Few countries offer gene therapy, its price is high, and researchers still follow its long-term safety. The conditioning uses the same high-dose busulfan as a transplant, with the same effect on fertility. For a child with a matched sibling, a transplant remains the established choice.
What are the results by risk class?
Pesaro's original series of 116 children under 16, treated with the regimen used from 1985, set the pattern still seen today.
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Matched-donor transplant in children under 16 by Pesaro class, three-year results
Pesaro class
Survival
Thalassemia-free survival
Return of thalassemia
Class 1, no liver enlargement or fibrosis
94 percent
94 percent
0 percent
Class 2, one factor
80 percent
77 percent
9 percent
Class 3, both factors
61 percent
53 percent
16 percent
Every class does better now.
Results have improved since 1990 for every class, with better conditioning, infection care and chelation. Even so, the message holds. A child transplanted young, with well-controlled iron and a healthy liver, has the best chance of a life without transfusions.
After a successful transplant the child stops transfusions and chelation. Iron already stored in the organs is removed over the following year or two by regular small blood draws or a short course of chelation, and yearly checks follow growth, puberty, fertility and the heart. Most children treated young go on to school, sport and adult life without the routine of the transfusion ward, the needles of the infusion pump at night and the steady worry over iron in the heart that shaped their early years, and families describe that change as the real measure of the transplant.
Bone marrow transplant for thalassemia FAQ
Can a bone marrow transplant cure thalassemia?
Yes. After a successful transplant the child makes normal blood and no longer needs transfusions or chelation.
What is the best age for transplant?
Younger is better. In the European registry, children transplanted before 14 did best.
Can a brother or sister with thalassemia trait donate?
Yes. A sibling with the trait is healthy and donates safely when the tissue type matches.
What if no sibling matches?
An unrelated donor search, a half-matched parent in selected cases, or gene therapy where available are the options the team will discuss.
How long will we stay in Istanbul?
Three to four months, until around day 100 after the transplant.
Can the donor sibling come too?
Yes. The donor sibling travels with the family, and the coordinator arranges the visa letter for both children.
References
Lucarelli G, Galimberti M, Polchi P, et al. Bone marrow transplantation in patients with thalassemia. New England Journal of Medicine. 1990;322(7):417-421.
Baronciani D, Angelucci E, Potschger U, et al. Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000-2010. Bone Marrow Transplantation. 2016;51(4):536-541.
Angelucci E, Matthes-Martin S, Baronciani D, et al. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel. Haematologica. 2014;99(5):811-820.
Locatelli F, Kabbara N, Ruggeri A, et al. Outcome of patients with hemoglobinopathies given either cord blood or bone marrow transplantation from an HLA-identical sibling. Blood. 2013;122(6):1072-1078.
Locatelli F, Thompson AA, Kwiatkowski JL, et al. Betibeglogene Autotemcel Gene Therapy for Non-β0/β0 Genotype β-Thalassemia. New England Journal of Medicine. 2022;386(5):415-427.
Editor's note
Written by the Biruni Hospital medical editorial team. Reviewed by Assistant Professor Kamil Değer DEVECİOĞLU, Pediatric Surgery.
