Introduction. Investigators from Johns Hopkins University pioneered the use of post-transplantation cyclophosphamide (PT-Cy) after T cell-replete haploidentical bone marrow (BM) infusion. A significant component of this scheme is tacrolimus (FK), associated to mycophenolate mofetil (MMF), to prevent immunological complications. FK is a calcineurin inhibitor, almost 100-fold more potent than cyclosporine A (CyA) in its inhibitory activity.

In this retrospective study, we analyzed 100 patients grafted with Haplo-SCT with PT-Cy, and receiving FK or CyA.

Patients and Methods. From April 2009 until April 2013, we analyzed 100 consecutive patients at two institutions (Institut Paoli Calmettes Marseille, France and Humanitas Cancer Center, Rozzano, Italy). Conditioning regimen was identical consisting of Fludarabine, Cyclophosphamide, and low dose TBI. GVHD prophylaxis consisted of Cy 50 mg/kg on days +3 and +4, FK or CyA and MMF. FK (at a total dose of 1 mg) was administered as a continuous infusion and then converted to oral formulation. CyA was dosed at 3 mg/kg as a continuous infusion and was then converted to oral formulation. MMF was administered at 45 mg/kg/day until day +35. FK, CyA and MMF were started on day +5. FK and CyA were tapered by day +100-180. Stem cell source was BM or peripheral blood stem cells (PBSC).

Results. Patient and transplant characteristics are shown in Table 1. The cumulative incidence of engraftment was similar between FK and CyA groups: 30-days absolute neutrophil count > 500 was 79% vs 91% (p 0.3), and unsupported platelet count more than 20 000 at 60 days was 77% vs 84% (p 0.7), respectively.

The incidence of grade 2-4 acute GVHD was 26% vs 30% (p 0.5) and the incidence of chronic GVHD was 13% vs 8% (p 0.9), respectively. The 2-year progression free survival (PFS) and overall survival (OS) were 53% vs 64% (p 0.2) and 65% vs 65%, respectively (p 0.7). The 2-year relapse incidence (RI) was 28% vs 12% (p 0.08) and the 2-year non relapse mortality was 16% vs 14% (p 0.7), respectively. In univariate analysis, only disease status (CR vs not CR) impacted the PFS, OS, and RI.

Patients were regrouped in 3 cohorts (1 patient excluded because received FK + PBSC): FK + BM (n 42), CyA + BM (n 14), and CyA + PBSC (n 43). 1-year NRM was not different (17% vs 14% vs 15%, p 0.8). Compared to FK +BM and CyA + PBSC, a trend in favor of CyA + BM was observed in terms of aGVHD (7% vs 24% vs 38%, p 0.05) and cGVHD (0 vs 13% vs 10%, p 0.9).

Conclusions. Although this is a retrospective study with potential selection bias, using CyA instead of standard FK did not seem to affect any major clinical outcome, with special interest for aGVHD and cGVHD. The NRM is acceptable in line with that published. GVHD incidence was lower in the group CyA + BM compared to other 2 groups. Disease status before haplo SCT was the only prognostic factor for survival and relapse.

Table 1.

Patient and transplant characteristics.

All ptsFKCSAp
    
 100  43  57   
Male Female 58/42  22/21 51/49 36/21 63/37 0.229 
Age (mean) 46  44  48  0.135 
Disease status at haplo       0.466 
CR 56  23 53 33 58  
PR 29  14 33 15 26  
SD   
PD  12  
Armand Risk       0.646 
Low  11  
Int 72  33 77 39 68  
High/Very high 19  16 12 21  
Previous transplant       <0.001 
Relapse after ALLO  14  
Relapse after HDC 40  21 49 19 33  
Sex D/R       0.533 
F/F 16  21 12  
F/M 21  19 13 23  
M/M 38  14 33 24 42  
M/F 25  12 28 13 23  
CMV D/R       0.009 
POS/POS 70  35 81 35 61  
NEG/NEG 18  16 28  
POS/NEG 11  14  
Donor       0.578 
children 26  12 28 14 25  
Mother 15  16 14  
Father 11  14  
Sibling 47  17 40 30 53  
Cousin       
Stem cell source       <0.001 
BM 56  42 98 14 25  
PBSC 44  43 75  
HCT-CI       0.007 
31  18 42 13 23  
1-2 23  13 30 10 18  
>3 46  12 28 34 60  
CD34 (mean) 4,4  3,5  5,2  <0.001 
All ptsFKCSAp
    
 100  43  57   
Male Female 58/42  22/21 51/49 36/21 63/37 0.229 
Age (mean) 46  44  48  0.135 
Disease status at haplo       0.466 
CR 56  23 53 33 58  
PR 29  14 33 15 26  
SD   
PD  12  
Armand Risk       0.646 
Low  11  
Int 72  33 77 39 68  
High/Very high 19  16 12 21  
Previous transplant       <0.001 
Relapse after ALLO  14  
Relapse after HDC 40  21 49 19 33  
Sex D/R       0.533 
F/F 16  21 12  
F/M 21  19 13 23  
M/M 38  14 33 24 42  
M/F 25  12 28 13 23  
CMV D/R       0.009 
POS/POS 70  35 81 35 61  
NEG/NEG 18  16 28  
POS/NEG 11  14  
Donor       0.578 
children 26  12 28 14 25  
Mother 15  16 14  
Father 11  14  
Sibling 47  17 40 30 53  
Cousin       
Stem cell source       <0.001 
BM 56  42 98 14 25  
PBSC 44  43 75  
HCT-CI       0.007 
31  18 42 13 23  
1-2 23  13 30 10 18  
>3 46  12 28 34 60  
CD34 (mean) 4,4  3,5  5,2  <0.001 

Disclosures

No relevant conflicts of interest to declare.

Author notes

*

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