Mismatched Haploidentical Bone Marrow Transplantation in a 10-year-old boy with relapsed refractory acute lymphoblastic leukemia, at Trichy

Vinod Gunasekaran ¹ , Subbiah RM ² , Prabhakaran Shankaralingam ³ , Senthil Kumar K ⁴ ,Rakesh Manohar ⁵ , Suresh Chelliah ⁶ , Senguttuvan D ⁶

¹ Paediatric Hematology Oncology BMT, Kauvery Hospital, Trichy, Tamilnadu, India

² Clinical Hematology BMT, Kauvery Hospital, Trichy, Tamilnadu, India

³ Transfusion Medicine, Kauvery Hospital, Trichy, Tamilnadu, India

⁴ Department of Anesthesia, Kauvery Hospital, Trichy, Tamilnadu, India

⁵ Paediatric Gastroenterology and Hepatology, Kauvery Hospital, Trichy, Tamilnadu, India

⁶ Department of Paediatrics, Kauvery Hospital, Trichy, Tamilnadu, India

*Correspondence:[email protected]

Case Presentation

A 10-year-old boy presented with two months history of fever, weight loss and body pains. On examination, he had pallor and hepatosplenomegaly. Investigations revealed a diagnosis of CD10 positive B- Acute Lymphoblastic Leukemia and cytogenetic and fluorescent in situ hybridization (FISH) showed a fusion of E2A/PBX1. CSF was negative for malignant cells. He was treated with chemotherapy as per Berlin-Frankfurt-Munich (BFM) protocol.

While on maintenance chemotherapy, he developed recurrence of excruciating body pains. Bone Marrow (BM) assessment showed features of disease relapse with 90% blasts and flowcytometry suggested B- Acute Lymphoblastic Leukemia (E2A/PBX1 positive). His disease was refractory to 2 cycles of salvage chemotherapy. Human leukocyte antigen (HLA) typing of the patient and family members were done which showed no HLA-matched donor. An unrelated donor search also couldn’t find a matched donor.

Poor prognosis was explained to the family. As they were keen to proceed with bone marrow transplantation with the best possible donor, patient was started on 3rdsalvage chemotherapy. After attaining disease control, the child was immediately taken up for bone marrow transplantation with father as the haploidentical donor (who had 7/10 match with the child).

After central line insertion, preparative regimen (Fludarabine and Melphalan) was administered to destroy the recipient’s bone marrow and suppress the immune system. Other prophylactic measures to prevent infections, sinusoidal obstruction syndrome and graft-versus-host disease were started appropriately as per standards. On 13 March 2023, peripheral blood stem cells were harvested from the father and were infused into the patient.

In haploidentical transplantation, T-cell depletion is key to minimize the risk of graft-versus-host disease. Ex-vivo T-cell depletion technique in the stem cell product is an expensive procedure. As an alternate, in vivo depletion of T-cells can be attained by administering high doses of Cyclophosphamide to the recipient 72 hours after the infusing the donor stem cells. However, additional administration of high dose chemotherapy post-transplant makes the procedure more challenging due to high risk of infections, mucositis and other treatment-related complications.

In our patient, post-transplant Cyclophosphamide (50 mg/kg/day) was administered on day +3 and day +4 post-transplant. Cyclosporine and Mycophenolate Mofetil were started on day +5.

Child had a total of 40 days hospital stay in a heavily immunocompromised status. Post-transplant complications included grade IV mucositis, and bacterial and fungal infections. He was managed with total parenteral nutrition, multiple antibiotics and transfusion of irradiated blood products. Gradually, the symptoms resolved with the recovery of blood counts as the father’s stem cells engrafted.

Post-transplant chimerism status showed 99.38% cells of donor origin in the child. He developed Cytomegalovirus (CMV) reactivation and grade IV graft-versus-host disease (gut stage 4 and liver stage 2) on day+29 post-transplant which was treated with Ganciclovir and immunosuppressive therapy (Steroid and Cyclosporine).

Child is currently asymptomatic. His disease and other co-morbidities are under control. He is on immunosuppressive and anti-viral therapy.