ISSN 1866-8836
Клеточная терапия и трансплантация

MP-02. Allogeneic hematopoietic stem cell transplantation in patients with secondary myelodysplastic syndrome or leukemia evolving from aplastic anemia and paroxysmal nocturnal hemoglobinuria

Irina K. Golubovskaya, Maria V. Marchenko, Nikolay Y. Tsvetkov, Anna A. Osipova, Elena V. Morozova, Alexander D. Kulagin

RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia


Contact: Dr. Irina K. Golubovskaya, phone: +7 (921) 785-26-24, e-mail: dr.irinagolubovskaya@gmail.com

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

Summary

Long-term survivors of aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) have an increased risk of developing myelodysplastic syndrome or acute myeloid leukemia (MDS/AML). Allogeneic stem cell transplantation (allo-HSCT) is the only curative treatment in patients with secondary MDS/AML evolving from AA and PNH. There are limited data on outcomes of allo-HSCT in this group. Overall survival (OS) in these patients is significantly lower than in patients with de novo MDS/AML. The aim of our study was to analyze the effectiveness of allo-HSCT in secondary MDS/AML after AA and AA/PNH.

Materials and methods

We analyzed 29 patients with MDS/AML after immunosuppressive treatment of АА and AA/PNH who underwent allo-HSCT between September 2007 and August 2023 from matched related (n=6), matched unrelated (n=15), 9/10 mismatched unrelated (n=4) or haploidentical donor (n=4). Four patients with AA/PNH before MDS received anticomlementary therapy. The median time between primary diagnoses and transformation to MDS/AML was 78 months (range 12-268). Monosomy 7 was detected in 16 (55 %), trisomy 8 in 4 (14 %) respectively. The median age at allo-HSCT was 26 years (range 11-39) and the median time from diagnosis MDS/AML to allo-HSCT was 6 months (range 1-18). Nine patients failed to respond to previous chemotherapy or hypomethylating therapy, 22 patients were heavy transfused and the median number of RBC and PLT transfusions was 35 and 40 doses, respectively. In most cases fludarabine-containing conditioning regimen was used (FluBu8 in 18 (62%), FluBu10 in 5 (17%) cases). The median dose of infused CD34+cell was 4.4×106/kg (range 1-9).

Results

Sustained engraftment was achieved in 20 of 29 patients (57%). One patient died of acute GvHD Grade IV and 2 died from infectious complication in primary graft failure. Two patients with refractory MDS (MDS-EB-2, CMML) after MAC relapsed at day +60 and +350 both patients died of disease progression after hypomethylating therapy (n=1) and second allo-HSCT (n=1). Ten patients who failed to engraft received second HSCT from the same (n=4) or alternative donor (n=6). One patient received third HSCT from alternative donor. Eight patients after second HSCT died of infectious complications due to primary graft failure (n=7) or acute GvHD Grade IV (n=1). Seventeen patients are alive with the median follow-up of 54 months (range 1-192). OS was 55.3 % (±9.8 %). The cumulative incidence of primary graft failure rate was 17.2 (95% CI: 6.3-32.7). Four of them received 2 cycles of hypomethylating agents as a prophylaxis of relapse after allo-HSCT, in 2 patients hypomethylating agents were used in cytogenetic relapse. All survivors are in complete remission with signs of limited chronic GvHD. At multivariate analysis, only one factor independently associated with lower survival, i.e., >5 % blast counts at the moment of allo-HSCT (p=0.009, 95% CI: 1.53–18.85, HR 5.37). Univariate analysis demonstrated that the numbers of CD34+ (p=0.04) and graft source (PBSC vs BM, p=0.048) were also significant prognostic factors for poor OS.

Conclusion

Primary graft failure and disease relapse remain a significant problem that has an impact on the outcome of allo-HSCT. Allo-HSCT in remission MDS-EB and AML or in case MDS-MLD increase OS in patients with secondary MDS/AML evolving after AA and PNH.

Keywords

Aplastic anemia, myelodysplastic syndrome, paroxysmal nocturnal hemoglobinuria, HSCT, allogeneic.


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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