Dharamshila Cancer Hospital and Research Centre, Vasundhara Enclave, New Delhi presents a case study of successful haploidentical (half matched) family donor stem cell transplantation in a patient with anti-donor antibodies: mix and match in the family
An 18-month-old child was diagnosed with acute myeloid leukaemia with abnormal cytogenetics. She was treated with standard induction chemotherapy, but failed to achieve a complete remission (CR). Further, high dose chemotherapy also did not produce a complete remission. In addition, she was found to be refractory to platelet transfusions due to high titre of anti-HLA antibodies (> 10,000 MFI). She was the only child and there were no suitable HLA matched unrelated donors in volunteer unrelated donor registries. Two cord blood units were 4/6 HLA matched with the patient, but the patient had anti-HLA antibodies against the mismatched HLA antigens. In fact she had the same against her own parents as well.
Although bone marrow transplantation (BMT) was the only option for the child, there were no matched donors within the family or in VUD registries. BMT from mismatched unrelated cord blood units was not possible due to anti-HLA antibodies. Haploidentical (half matched) family donor transplantation is considered as an option in such situations. However, the patient had anti-HLA antibodies directed against parental HLA antigens as well. Graft from haploidentical family donors in patients with such high titre of anti-HLA antibodies invariably results in failure. Treatment to reduce the antibody levels was not successful either.
Options were extremely limited in this case. Further, chemotherapy with high dose cytarabine and cladrabine resulted in reduction in the burden of leukaemia, but it was very clear that a cure was not possible with chemotherapy alone. Innovation was the need of the hour. The team of BMT physcians at the Dharamshila hospital, Dr Sarita Jaiswal and Dr Suparno Chakrabarti decided that the uncle of the child can be the donor, who was HLA-matched with the father of the child, despite high levels of anti-donor antibodies. Peripheral Blood Stem Cells (PBSC) collected from the uncle were depleted of T and B cells and only CD34+ stem cells were infused at very high numbers, after conditioning with high dose chemotherapy. Two weeks later there was no sign of engraftment. The child was extremely sick with gram negative sepsis and the bacteria isolated was resistant to carbapenems. The only thing that kept the child going was regular granulocyte infusions from the relatives.
Despite the apparent setback, the result was anticipated by the doctors and one of the reasons for using the uncle as a donor and not the father was clear when the HLA antibodies against the HLA antigens against the father were no longer detected. High dose of CD34 cells from the uncle had mopped up the antibodies. Stem cells from the father were infused to the child after minimum amount of conditioning. The graft from the father started working after 10 days and the child was free from leukemia with 99 per cent donor cells at an assessment at 30 days.
Haploidentical BMT is the only resort for patients without a fully HLA matched donor. Yet, many patients who are transfused with blood products which are not leucodepleted can develop clinically significant HLA antibodies. BMT from these donors is bound to fail in these circumstances. Yet, this unique and innovative approach using a double transplant approach might be useful in selective cases.