PB2367 POST‐TRANSPLANT CYCLOPHOSPHAMIDE VERSUS METHOTREXATE BASED REGIMEN IN ALLOGENIC HEMATOPOIETIC STEM CELL TRANSPLANTATION, CLINICAL OUTCOME (EGYPTIAN EXPERIENCE)
Authors: Mohamed H. , Moussa M. , Ibrahim R. , Soryal G. , Negm M. , Hosainy A. E.L. 
Published: June 2019

Background:

Graft‐versus‐host disease (GVHD) remains one of the main life‐threatening complications after allogeneic stem cell transplantation (HSCT). The standard GVHD prophylaxis strategy is mostly based on the use of calcineurin inhibitors alone or in combination with other immunosuppressive (IS) drugs. With the increased use of HSCT from unmanipulated haploidentical donor, adapted GVHD prophylaxis has been proposed. Among those, pioneered the use of high‐dose post‐transplant cyclophosphamide (PT‐Cy) in combination with other IS drugs reporting a low incidence of acute (a) and chronic (c) GVHD and low transplant‐related mortality.

Aims:

To compare the clinical outcome of allogenic HSCT after post‐ transplant cyclophosphamide versus methotrexate based regimens

Methods:

we included 137 patients aged from 16‐65 years old from Bone marrow transplantation Units in Egypt (Ain Shams University Hospitals and Maadi Armed Forces Medical Compound) who subjected to allogeneic HSCT to treat hematological malignancies using myeloablative regimens according to each disease state in 1st complete remission (CR), 2nd CR who received either methotrexate (MTX) and cyclosporine –A (CSA) or PT‐Cy in combination with other immunosuppressive drugs(IS) as GVHD prophylaxis. They divided into 2 groups: One hundred and two patients received (MTX) and (CSA) (group 1); 35 received PT‐Cy in combination with two IS drugs: (CSA) and mycophenolate‐mofetil (MMF) (group 2). Transplants were performed from 2010 to 2014 and median follow‐up was 60 months after informed consent, comparative study was held as regard engraftment, CMV reactivation, GVHD, overall survival, disease free survival.

Results:

90.2% of Patients received MTX and CSA (group1) had neutrophil engraftment at day12.91 ± 5.67SD, whereas 91.4% of patients in (group 2) had neutrophil engraftment at day14.69 ± 2.57SD, as regard platelet recovery Mean day of platelet recovery was 14.67 ± 1.89SD in (group 1) and14.69 ± 5.48SD in (group 2).

No statistical significant difference as regard CMV reactivation between both groups,it was about 26.5 % in (group 1) and 31.4% in (group 2).

Incidence of aGVHD was 31.4%, 28.6% in group 1, 2 respectively, 40% of (group 1) experienced grade IV while 50% of (group 2) had grade II.The addition of two IS drugs to PT‐CY was associated with reduced risk of extensive cGVHD to 17.1% in (group 2) in comparison to 56.9% in (group 1) with high statistical significance. (p‐ value <0.001)

Overall survival (OS) at 5 years was 40.2%, 53.6% for both groups, respectively (p value = 0.76), while 5 years disease free survival (DFS) was 81.3%, 71.2% in both groups respectively(p value = 0.32). upon Correlation of overall survival (months) with CMV reactivation, aGVHD, cGVHD and engraftment in (group I), there is statistically significant correlation with cGVHD and engraftment (p value 0.018, <0.001) respectively.While in (group2) there is statistically significant correlation with engraftment (p value <0.001)

As regard disease free survival (months) correlation with CMV reactivation, aGVHD and cGVHD in both groups, a statistical significant correlation was detected with cGVHD.(p value = 0.03) in (group1).

Summary/Conclusion:

For GVHD prophylaxis in HSCT, the addition of IS drugs to PT‐Cy enhances its effect and reduces the risk of severe cGVHD, reducing mortality and improving overall survival