Bone Marrow Transplant For Aplastic Anemia

In 599 children with severe aplastic anemia, 87 percent of those given a sibling bone marrow transplant were alive and free of treatment failure. With immune-suppressing drugs as first treatment the figure was 56 percent.

Overall survival in that Japanese study was high with both approaches, 92 percent after transplant and 88 percent after drug treatment, since children whose drugs failed could still be rescued (Yoshida and colleagues, Haematologica, 2014). The difference lay in how many needed rescuing. Severe aplastic anemia is a failure of the bone marrow, in most cases because the immune system has turned on the blood-forming stem cells, and it leaves a person short of red cells, white cells and platelets all at once. A bone marrow transplant for aplastic anemia replaces the damaged stem cells and the misdirected immune system together, and for younger patients with a matched brother or sister it is the treatment of first choice. This page explains who should have a transplant and who should have drug treatment first, how the transplant differs from those done for leukemia, what the large registries show, and how patients from abroad can plan care at Biruni Hospital in Istanbul.

When the marrow stops working

Aplastic anemia affects two or three people per million each year in Europe and somewhat more in Asia. Nobody should mistake it for cancer. The marrow simply stands empty, its blood-forming cells replaced by fat, and the consequences are tiredness and breathlessness from anemia, infections from a lack of white cells, and bruising or bleeding from a lack of platelets.

Doctors grade the disease by blood counts, because the grade decides how fast treatment must begin.

Tests that must come first

A trephine biopsy confirms the empty marrow and excludes leukemia and myelodysplasia. A chromosome breakage test looks for Fanconi anemia and telomere testing for related inherited conditions, since both can look identical to acquired disease in a child or young adult and both change the transplant plan fundamentally. Flow cytometry looks for a PNH clone. Virus screening and a drug history complete the picture.

Tissue typing cannot wait. Request it for the patient and every full sibling on the day of diagnosis.

Transplant or drug treatment

1. Age. The younger the patient, the stronger the case for transplant. Guidelines draw the line for first-line sibling transplant at around 40, and some centers extend it to 50 in fit patients.
2. Donor. A matched brother or sister makes transplant the first choice in younger patients. Without one, most patients start with drugs while an unrelated donor search runs.
3. Severity. Very severe disease leaves less time for drugs to work, since responses take three months or more.
4. Other illness and infection. Active fungal infection or poor organ function raises transplant risk and has to be weighed.
5. The patient's own view. A one-time risk with a high chance of cure, against a gentler start with a less certain finish.

The usual pathway

What the studies show

The European registry analyzed 1,886 sibling transplants for acquired aplastic anemia performed between 1999 and 2009. Survival with bone marrow as the cell source was 90 percent under the age of 20 and 74 percent above it. With cells collected from blood it was 76 and 64 percent (Bacigalupo and colleagues, Haematologica, 2012).

That study identified what worsens the outlook. Age over 20 doubled the risk of death. A delay of more than 114 days between diagnosis and transplant raised it by 30 percent, conditioning without antithymocyte globulin by 60 percent, and the use of blood-derived stem cells by 60 percent, largely through more graft-versus-host disease. Age cannot be changed. Everything else on that list can.

The drug alternative

The RACE trial randomized 197 previously untreated patients to standard immune suppression with or without eltrombopag, a tablet that stimulates stem cells. At six months 68 percent had responded with the added drug and 41 percent without it, and the first response came at a median of 3.0 months against 8.8 (Peffault de Latour and colleagues, New England Journal of Medicine, 2022). Complete responses at three months remained a minority, 22 against 10 percent. Drug treatment works. It has improved. It still restores counts more often than it restores a fully normal marrow.

How this transplant differs

Before the transplant

Weeks between diagnosis and admission are dangerous, and several precautions protect both the patient and the future graft.

• Blood products are filtered and irradiated, and never donated by family members, because exposure to a relative's cells can prime rejection of the graft.
• Transfusions are kept to what is needed. Heavily transfused patients reject more often.
• Any fever is treated as an emergency with antibiotics in the hospital.
• Antifungal protection is started in very severe disease.
• Bleeding risks are reduced, which means a soft toothbrush, no aspirin or ibuprofen, and hormonal control of heavy periods.

From admission to recovery

Expect an admission of four to five weeks.

• Days minus 7 to minus 1. Central line, conditioning drugs, fluids to protect the bladder from cyclophosphamide, and the first doses of antithymocyte globulin, which can cause fever and chills.
• Day zero. The donor gives marrow under general anesthetic that morning, and it is infused in the afternoon.
• Days 1 to 21. Protective isolation, antibiotics, transfusions, and cyclosporine with short-course methotrexate to prevent graft-versus-host disease.
• Days 14 to 28. Neutrophils recover first, then platelets. Marrow engrafts a little more slowly than blood stem cells would, a price worth paying.
• To day 100. Clinic once or twice weekly, chimerism tests to confirm that blood cells are donor, and monitoring of cyclosporine levels and kidney function.

People who arrive at transplant free of infection, lightly transfused and within three months of diagnosis do best. Speed matters more here than in almost any other transplant.

Risks

Living afterward

The donor's part

Brothers and sisters ask what donation will cost them. Very little.

Before anything else the donor has a medical check, blood tests and, where an inherited marrow condition has not been firmly excluded in the patient, the same genetic tests, since a sibling can carry the same fault without knowing it and a graft from that sibling would fail. On the day, marrow is drawn from the back of the pelvis through needles under a general anesthetic lasting an hour or so. The volume depends on the weight of the recipient, and the body replaces it within a few weeks. Donors go home the next day with a sore lower back, take simple pain relief for up to a week, and are told to avoid heavy lifting for a fortnight. Iron tablets help. Serious complications of marrow donation are very rare, and international donor registries have tracked them across many tens of thousands of harvests. Children can donate to a sibling with the consent of their parents and, in keeping with good practice, an independent assessment that the child understands and agrees as far as age allows.

Blood stem cell collection from the arm is easier for the donor and worse for this particular patient, for the reasons the registry data make plain, so a donor who is offered the choice should know that marrow is the generous option.

Coming from abroad

Time runs short in this disease. Send the blood counts, the marrow report, the transfusion record and any tissue typing at once, and the hematology team will review them without charge and reply in writing. If typing has not been done, the reply explains how samples from brothers and sisters can be tested. Patients with very severe disease may need to be stabilized at home before flying, with platelets above a safe level and no active infection, and the two medical teams should speak directly about timing. The donor sibling travels too. Ten to fourteen days is enough. For the patient, plan on three to four months in Istanbul, covering the admission and close follow-up to day 100. Doctors consider you fit to fly when counts are stable without transfusion, cyclosporine levels are steady and no infection is active, and the team supplies a written schedule for the hematologist who will supervise the slow taper once you are back home.

One coordinator from the international patients office handles arrangements from the first message through discharge and answers the same WhatsApp number afterward. The office works in English, Arabic, French, Russian, Serbian, Romanian and Spanish and books interpreters for other languages. It arranges the visa invitation letter for patient, donor and companions, airport transfers, daily transport and accommodation near the hospital. Ward rooms have a companion bed. The kitchen prepares halal, vegetarian and diabetic meals. A prayer room is on site, and a request for a female physician is met wherever the rota allows.

Cost

The written estimate follows the file review. Hospitals in this market price a sibling transplant as a package covering donor workup, marrow harvest, conditioning, the admission and a defined follow-up period, and they itemize donor search fees, extra nights and treatment of complications.

Confirm what the package includes.