Overcoming Challenges and Performing First Paediatric Allogenic Bone Marrow Transplantation in Trichy

Vinod Gunasekaran¹, Subbiah RM², Prabakaran Sankaralingam³, Senthil Kumar K⁴, Suresh Chelliah⁵, Senguttuvan D⁵.

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

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

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

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

⁵Department of Paediatrics, Kauvery Hospital, Trichy, Tamilnadu, India

A 4-year-old boy presented with fever, skin infection and abdominal distension on 04 May 2019. On examination, he had pallor and hepatosplenomegaly. Investigations revealed Hb 5.9, WBC 4700, platelets 19000 and peripheral smear showing blasts. Bone marrow smear and flowcytometry showed CD10 positive B-ALL, Karyotype 46 XY [20] and FISH – extra copies of RUNX1. CSF was negative for malignant cells. He was treated as standard risk B-ALL as per BFM 2000 protocol.

While on maintenance chemotherapy, he developed inter-current problems since March 2021 in the form of drop in counts, fever, splenomegaly, facial nerve palsy (transient) and bone pains. X-ray left femur showed periosteal reaction (laminated pattern) in diaphyseal region with metaphyseal growth arrest lines. BM assessment on 24 May 2021 showed normal morphology with negative MRD. Eventually, he presented frank leukemia (high WBC with blasts) on 31 July 2021. Peripheral smear showed 60% blasts and 20% atypical monocytoid cells and flowcytometry revealed acute myeloid leukemia (positive for cMPO, CD123, CD66c, CD38, CD4, CD56, CD33, CD13, CD64, CD15); Karyotype 46XY [10]; FISH – KMT2A rearrangement in 70% population. For his second malignancy, he received 2 courses of chemotherapy – Daunorubicin + Ara-C (3+7) and Bortezomib + FLAG. Bone marrow evaluation after both the cycles were in remission.

In view of poor prognosis of his condition, option of bone marrow transplantation was offered to the parents. HLA typing of the patient and his 8-year-old elder sister were done which showed a 10/10 match. After thorough pre-transplant work-up of patient and donor, patient was admitted on 12 October 2021. 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 19 October 2021, peripheral blood stem cells were harvested from the sister and were infused into the patient. During infusion, child developed fever, chills and rigors. Infusion was withheld and IV Avil and PO Paracetamol were given. After 30 minutes, infusion was restarted.

On day +2, child developed fever, chills and rigors, for which blood culture was sent and child was started on IV Cefoperazone-Sulbactam. As fever persisted for more than 24 hours, antibiotics were escalated to Meropenem and Amikacin. Later, blood culture grew Pseudomonas, which was sensitive to ongoing antibiotics and hence were continued. Child had oral ulcers and prolonged diarrhea during post transplant neutropenic phase, which was managed with intravenous fluids, vitamins, potassium, and zinc supplementation. Symptoms settled with recovery of blood counts. Irradiated blood products were transfused during post-transplant period. Neutrophils and platelets engrafted on day +13. During engraftment period, child had fever with chills. Repeated blood cultures were negative and blood counts showed a steadily increasing trend. There were no other features of engraftment syndrome. Hence, fever was managed with antipyretics. Cyclosporine dose was adjusted based on trough level monitoring. FISH X/Y analysis on patient’s peripheral blood sample on day +15 showed 100% XX (100% donor chimerism). Child was discharged on day +17 and is continued on immunosuppression.

The entire process had many challenges, which were overcome by a team effort and adequate planning. Trichy Moon Rock Round Table trust 108 provided generous financial assistance to complete the treatment of the patient.