ISSN 1866-8836
Клеточная терапия и трансплантация

NM-04. The experience of hematopoietic stem cell transplantation for thalassemia major at the Morozov Children’s Hospital

Bulat M. Kurmanov, Irina O. Vlasova, Anna V. Lifshits, Georgiy Z. Seregin, Maria R. Zhuravel, Gleb O. Bronin, Ella V. Kumirova, Michael A. Maschan

Morozov City Children’s Hospital, Moscow, Russia


Contact: Dr. Bulat M. Kurmanov, phone: +7 (916) 508-27-50, e-mail: bulat.kurmanov@mail.ru

doi 10.18620/ctt-1866-8836-2023-12-3-1-176

Summary

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative approach to treatment of thalassemia major. The aim of our study was to summarize our experience with HSCT in thalassemia major treatment.

Materials and methods

During the period from 2019 to 2023, we performed 29 HSCTs in patients with thalassemia. In 27 cases, the diagnosis was assessed by genetic tests, in 2 cases – only by hemoglobin electrophoresis. Pathogenic variants were homozygous in 8 cases and compound heterozygous in 19 cases. The age of patients at the time of HSCT ranged from 2 to 14 years (mean 7 years). In 26 cases, pre-transplant immunosuppressive therapy was performed with fludarabine, dexamethasone and rituximab (6 patients received 1 course, 4 children – 2 courses, 13 patients – 3 courses, 2 children – 4 courses, 5 courses were performed in one case). Daratumumab was additionally used in 20 cases. All patients in the process of preparing for HSCT underwent regular blood transfusions and chelation therapy. MRI of the liver and heart was performed before HSCT in 19 children. 17 cases of liver overload and 2 cases of cardiac overload with iron were observed.

Results

All patients underwent myeloablative conditioning regimen, 25 (86%) – on the basis of treosulfan, 4 (14%) - on the basis of busulfan. The sources of HSCs were peripheral blood stem cells for 26 patients (90%), bone marrow - for 3 (10%). Nine patients (31%) underwent HSCT from 10/10 matched unrelated donor; 10 (34%), from 9/10 matched unrelated donor; 4 (14%), from a haploidentical donor; 6 (21%), from matched related donor. The average dose of CD34+ cells was 6.3×106/kg. Graft-versus-host disease (GvHD) prophylaxis was performed in 2 cases with cyclosporine and methotrexate. 27 children received post-transplant cyclophosphamide. 13 of them received also calcineurin inhibitors (CNI) as monotherapy, but 14 of them – CNI and mycophenolate mofetil in combination. Engraftment was achieved in 28 cases. The median engraftment time was 21 days. Primary non-engraftment was observed in 1 patient, who showed recovery of his own hematopoiesis. The child is alive now, second HSCT was not performed. Graft rejection was recorded in 1 case on day +100. After prolonged immunosuppression this child underwent a successful second HSCT from 9/10 matched unrelated donor. Acute GvHD, grade 1 skin lesion, was noticed in 2 patients, grade 3 skin involvement – in 1 child. Severe forms of acute GvHD were not observed in any of the patients. Chronic GvHD was revealed in 3 patients: 1 – lung affection, 1 – joints, and 1 – oral cavity involvement. Overall, 3 patients died. The causes of death were cytomegalovirus pneumonia, chronic GvHD with severe lung damage and respiratory distress syndrome along with sepsis during the engraftment period. 24 patients are transfusion-independent up to now. One child is still transfusion-dependent at the early terms after HSCT. Severe complications associated with HSCT (grade 3 on the CTCAE v. 4.0 scale) were observed in 4 patients: thrombotic microangiopathy, multisystem inflammatory syndrome, veno-occlusive disease of liver, and hemorrhagic cystitis. All these complications were cured successfully without consequences. One should note that the average age of 11 years at the time of HSCT was documented for the deceased patients and survivors with severe complications. At the same time, younger age (a mean of 6 years old) was documented for a group of 22 patients who underwent HSCT without significant complications (p=0.001).

Conclusion

Our experience showed positive results of HSCT in patients with thalassemia major. The most significant prognostic factor is the age of patients at the time of HSCT.

Keywords

Thalassemia, allogeneic hematopoietic stem cell transplantation.


Supplement 12-3
09/30/2023

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doi 10.18620/ctt-1866-8836-2023-12-3-1-176

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