A bone marrow transplant replaces a child's blood-forming system with donor cells and cures leukemia that chemotherapy alone cannot control. A brother or sister, an unrelated volunteer or a parent can be the donor. This guide covers who needs a transplant, donor choice, conditioning, the 100 days, life afterward and the months to plan in Istanbul.
About This Department
Pediatric Hematology and Oncology
A bone marrow transplant replaces a child's blood-forming system with healthy cells from a donor, giving a cure to children whose leukemia chemotherapy alone cannot control. Matching the timing, the donor and the preparation to each child decides the result.
Chemotherapy alone cures most children with leukemia, and they never need a transplant. For a smaller group, those with very high-risk disease, leukemia that has come back, or acute myeloid leukemia with certain features, an allogeneic stem cell transplant offers the best chance. High-dose treatment clears the marrow, and stem cells from a brother or sister, an unrelated volunteer or a parent rebuild it, bringing a new immune system that attacks remaining leukemia cells. In the international FORUM trial, 91 percent of children with high-risk acute lymphoblastic leukemia were alive two years after a transplant prepared with total body irradiation. Send us your child's diagnosis, treatment so far, latest marrow results and the tissue types of brothers, sisters and parents if available, and the pediatric transplant team will tell you whether a transplant is advised, which donor fits and how to plan.
91%
Two-year survival after radiation-based preparation, high-risk ALL, FORUM trial
71%
Five-year survival free of relapse and chronic GVHD with a parent donor, Rome trial
3 to 4 months
In Istanbul for most families
Free
Pediatric transplant team's review of your child's file
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When a transplant is considered in childhood leukemia
Situation
Transplant advised when
Acute lymphoblastic leukemia, first remission
Very high-risk genetics, or leukemia still measurable after the first months of treatment
Acute lymphoblastic leukemia, relapse
Relapse during treatment or soon after it, once a second remission is reached
Acute myeloid leukemia
Poor response to the first course, high-risk genetic changes, or relapse
Rarer leukemias
Juvenile myelomonocytic leukemia and some forms of myelodysplasia
Our study indicates that HLA-matched related BMT is an effective treatment for pediatric patients with intermediate-risk AML in first CR.
Children's Oncology Group analysis of 1,373 children, Journal of Clinical Oncology, 2008
What a bone marrow transplant is
Doctors now call it a hematopoietic stem cell transplant, since the cells come from the donor's bone marrow, from blood after injections that release stem cells, or from umbilical cord blood. First the child receives conditioning, high-dose chemotherapy with or without total body irradiation, which destroys the leukemia and the child's own marrow. The donor cells then go in through a vein like a blood transfusion, settle in the bones and start making new blood within two to four weeks.
The new immune system matters as much as the high doses. Donor immune cells recognize leftover leukemia cells as foreign and destroy them, an effect called graft-versus-leukemia.
Measuring the leukemia that remains
Sensitive tests find one leukemia cell among ten thousand or more normal cells, far below what a microscope shows. The German ALL-REZ BFM group followed 91 children transplanted for relapsed acute lymphoblastic leukemia and found this level, called measurable residual disease, to be the only independent predictor of outcome. Children who reached transplant with fewer than one leukemia cell in ten thousand did far better, and the team therefore checks it before every transplant.
MRD is an important predictor for post-transplantation outcome.
ALL-REZ BFM prospective study of 91 children, Journal of Clinical Oncology, 2009
Remission comes first
A transplant cannot rescue a child whose leukemia is still active in the marrow. The team brings the leukemia down to the lowest level it can measure before conditioning starts, and adds newer treatments such as immunotherapy when chemotherapy alone falls short.
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Residual leukemia before transplant and outcome, relapsed ALL, 91 children
Residual disease before transplant
Event-free survival
Relapse
Below one cell in 10,000
60 percent
13 percent
One cell in 10,000 or more
27 percent
57 percent
Who can be the donor?
The search starts early, while chemotherapy continues, so that no time is lost once the child is ready.
A brother or sister, each with a one in four chance of being a full tissue match.
An unrelated volunteer.
Umbilical cord blood from a public bank, mainly for smaller children.
A parent, who always shares half the tissue type and is ready at once.
A parent as donor
The Rome trial
Bambino Gesù Children's Hospital in Rome treated 80 children with acute leukemia using a transplant from a half-matched relative, in most cases a parent. In the laboratory, the alpha-beta T cells most likely to attack the child's body were removed before the cells went in. Only 5 percent died of causes other than leukemia, 24 percent relapsed, and no child developed extensive chronic graft-versus-host disease.
Five years later, 71 percent had survived without relapse or chronic graft-versus-host disease. Children transplanted from a matched brother, sister or unrelated donor in the same years did no better. Families no longer need to wait months for a perfect match when the leukemia cannot wait.
These data indicate that haplo-HSCT after αβ T- and B-cell depletion represents a competitive alternative for children with AL in need of an allograft.
Prospective trial of 80 children, Blood, 2017
Graft-versus-host disease
When the new immune system attacks the body
Donor immune cells sometimes turn on the child's skin, gut or liver. A rash starting on the palms, soles or ears, diarrhea and cramps, or yellow eyes are the first signs. Mild forms respond to creams or a short steroid course. Prevention starts before the transplant with careful donor choice, cell processing in the laboratory and medicines given for the first months.
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Rome trial of half-matched transplants, 80 children
Outcome
Result
Deaths not caused by leukemia
5 percent
Relapse
24 percent
Mild, skin-only acute graft-versus-host disease
30 percent
Alive at five years, free of relapse and chronic graft-versus-host disease
71 percent
What happens during the transplant?
1
Assessment
A marrow test for residual leukemia, heart, kidney, lung and dental checks, infection screening, and a central line placed in a large vein.
2
Fertility
Before conditioning, the team discusses fertility preservation, from sperm banking for teenage boys to ovarian tissue freezing for girls.
3
Conditioning
Six to eight days of chemotherapy, with or without total body irradiation in small doses twice a day.
Radiation or chemotherapy before the transplant
Doctors worried for years over the late effects of total body irradiation on growth, hormones, learning and fertility, and hoped chemotherapy could replace it. The FORUM trial, run in 21 countries, randomized 417 children and young people aged 4 to 21 with high-risk acute lymphoblastic leukemia in remission to radiation with etoposide or to a chemotherapy-only combination. Radiation won clearly. At two years, 91 percent of children given radiation were alive against 75 percent without it, relapse fell from 33 to 12 percent and deaths related to treatment from 9 to 2 percent, a difference large enough that the independent committee stopped the trial early and every participating center changed its practice.
Children under four, whose developing brains and bodies are most sensitive to radiation, and children with acute myeloid leukemia still receive chemotherapy-only conditioning with busulfan or treosulfan, fludarabine and thiotepa, with busulfan blood levels adjusted for each child.
Fever during the low-count weeks
From conditioning until the new marrow works, the child has almost no white cells. A temperature of 38 degrees or more, shivering, sudden tiredness or a drop in blood pressure needs the transplant team at once, day or night, since antibiotics started within the hour save lives.
We therefore recommend TBI plus etoposide for patients > 4 years old with high-risk ALL undergoing allogeneic HSCT.
FORUM randomized trial of 417 patients, Journal of Clinical Oncology, 2021
From day zero to going home
The cells go in on what the team calls day zero.
Engraftment
The weeks in the protected room
For two to four weeks the child has very low counts, with transfusions, antibiotics, mouth care and feeding support. A parent stays in the single room throughout. Engraftment, the day the white cells return, is the first milestone, and blood tests then show how much of the marrow comes from the donor.
1
Weeks one to four
Low counts, transfusions and infection prevention in a single room with filtered air.
2
Weeks four to eight
White cells return. 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 and infection, weekly checks and marrow tests.
Stable blood counts without frequent transfusions.
No active infection or uncontrolled graft-versus-host disease.
Eating and drinking enough, with every medicine now taken by mouth rather than through the central line, so that the family can manage the routine at home without daily hospital visits.
A receiving pediatric hematologist at home who has the full written plan.
Days, cost and the trip
Plan three to four months. Tests for the child and the donor take one to two weeks and conditioning a week. Families fly home around day 100.
Cost depends on the donor search, the donor type, laboratory processing of the cells, the conditioning, the weeks in hospital and the medicines afterward. The coordinator explains each part once the team has reviewed the file.
One coordinator stays with the family from the first message, arranging the visa invitation letter, transfers and a furnished apartment near the hospital. Play specialists and teachers help the weeks pass, and the team works in seven languages with halal meals and a prayer room available.
Back home
Care continues with your local team
The transplant physicians review blood counts, drug levels and donor cell results sent by your local team and stay reachable on the same WhatsApp number for years. Doctors taper the medicines that prevent graft-versus-host disease over months. Never stop them suddenly. Report any new rash, diarrhea or fever the same day.
Vaccines again
Inactivated vaccines restart from six months to a year after transplant.
Live vaccines such as measles wait until at least two years, and only once immunity has recovered.
Brothers, sisters and parents keep their own vaccines up to date to protect the child.
What is life like after transplant?
Long-term survival
Children well at two years mostly stay well. They still need care for life. The Bone Marrow Transplant Survivor Study followed 1,479 people of all ages who had survived at least two years after an allogeneic transplant. Fifteen years on, 80 percent of those free of disease at entry were alive. Even so, their death rate stayed twice that of the general population, mostly from late relapse and chronic graft-versus-host disease.
This study demonstrates that mortality rates remain twice as high as that of the general population among 15-year survivors of HCT.
Bone Marrow Transplant Survivor Study of 1,479 patients, Blood, 2007
Growth and puberty slow in some children, the thyroid fails in others, fertility falls, and radiation adds a risk of cataracts and second cancers years later. None of this is certain. Each problem responds to early care, and a yearly review of growth, hormones, heart, lungs, eyes and school progress, ideally in a long-term follow-up clinic, finds them while they are small, long before a child or a teacher would notice that growth has stalled, energy has dropped or schoolwork has become harder than it should be.
Is the approach different for myeloid leukemia?
Yes.
Risk decides the benefit
In acute myeloid leukemia, the question is which children gain from a transplant in first remission. The Children's Oncology Group combined four trials with 1,373 children and compared those assigned to a matched sibling transplant with those given chemotherapy alone. In the intermediate-risk group, eight-year disease-free survival was 58 against 39 percent and overall survival 62 against 51 percent, both in favor of transplant.
In the favorable-risk and poor-risk groups, survival did not differ significantly. Children with favorable genetics therefore avoid a first-remission transplant, and for the highest-risk group newer approaches before and after transplant are the focus of current trials.
Bone marrow transplant for childhood leukemia FAQ
Does every child with leukemia need a bone marrow transplant?
No. Most children are cured with chemotherapy. A transplant is advised for very high-risk or relapsed leukemia and some forms of acute myeloid leukemia.
Can a parent be the donor?
Yes. A parent shares half the tissue type, and in a Rome trial of 80 children with alpha-beta T-cell depletion, results matched those with fully matched donors.
What is the survival rate?
It depends on the leukemia and its response. In the FORUM trial, 91 percent of children with high-risk ALL were alive two years after a radiation-based transplant.
Why is total body irradiation used if it has late effects?
For children over four with high-risk ALL, the FORUM trial found fewer relapses and better survival than with chemotherapy alone.
How long will we stay in Istanbul?
Three to four months, until around day 100 after the transplant.
Can a parent stay with the child?
Yes, in the room, throughout.
References
Peters C, Dalle JH, Locatelli F, et al. Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study. Journal of Clinical Oncology. 2021;39(4):295-307.
Locatelli F, Merli P, Pagliara D, et al. Outcome of children with acute leukemia given HLA-haploidentical HSCT after αβ T-cell and B-cell depletion. Blood. 2017;130(5):677-685.
Bader P, Kreyenberg H, Henze GH, et al. Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: the ALL-REZ BFM Study Group. Journal of Clinical Oncology. 2009;27(3):377-384.
Horan JT, Alonzo TA, Lyman GH, et al. Impact of disease risk on efficacy of matched related bone marrow transplantation for pediatric acute myeloid leukemia: the Children's Oncology Group. Journal of Clinical Oncology. 2008;26(35):5797-5801.
Bhatia S, Francisco L, Carter A, et al. Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study. Blood. 2007;110(10):3784-3792.
Editor's note
Written by the Biruni Hospital medical editorial team. Reviewed by Assistant Professor Kamil Değer DEVECİOĞLU, Pediatric Surgery.
