Introduction

Human leukocyte antigens (HLA)-matched sibling or unrelated donor are available for around only 50-60% of patients. However, for patients without a suitably matched related donor, Alternative donors such as mismatched unrelated, cord blood and mismatched family donors could be searched. The aim of this retrospective study was to compare the results of graft source on outcome of patients after haploidentical related donor (Haplo), and the unrelated umbilical cord blood (UCB) transplantation in the setting of Non myeloabalative conditioning regimen (NMA).

Patients and methods

We retrospectively analyzed outcomes in 150 adult patients with high risk hematologic diseases who received Allo-SCT from alternative donors from two centers (Institut Paoli-Calmettes at Marseille France and Humanitas cancer center at Rozzano, Italy): These two centres have been applying common transplant approaches and procedures during the study period. 69 patients received Haplo and 81 patients received UCB. In the UCB group, the NMA regimen consisted of fludarabine (Flu), cyclophosphamide (Cy) and low dose TBI (2 Gy) combination in the two groups. The GVHD prophylaxis consisted of Cyclosporine A (CsA) and MMF in all patients in the two groups. In the Haplo group all patients received also 50 mg/kg Cy at day 3 and 4 post transplant. Of note, supportive care was the same during the whole study period. CMV infection management was also homogeneous. Patient characteristics are shown in Table 1.

Table 1

Patient and transplantation characteristics:

Characteristic Total =150 patients Haplo transplant (n = 69) CB transplant (n = 81) P value 
Patients Age years (median) [range] 44 (19-68) 47 (18-66)  
Patients sex   ns 
Male 39 (57) 46 (57)  
Female 30 (43) 35 (43)  
Disease type    
AML 3 (4) 37 (46) <0.0001 
ALL 1 (1) 14 (17) <0.0001 
NHL 24 (35) 14 (17) ns 
HL 30 (43) 2 (2) <0.0001 
MM 4 (6) 2 (2) ns 
CLL 5 (7) 4 (5) ns 
CML 1 (1) ns 
MDS/ MPS 2 (3) 7 (9) ns 
Status of disease    
CR 37 (54) 56 (69) ns 
PR/SD 24 (35) 12 (15) 0.04 
PD 8 (11) 13 (16) ns 
Donor type    
Sibiling 32 (46)   
Parent 18 (26)   
Child 18 (26)   
cousin 1 (2)   
Donor/recipient sex mis-match 34 (49) 56 (69) ns 
ABO incompatibility 24 56 0.02 
Conditioning regimen    
Flu 5+Cy 1+ TBI 75 (93)  
Flu 5+Cy 2+ TBI 69 (100) 6 (7)  
Stem cell source    
Peripheral Blood 19 (28)   
Bone Marrow 50 (72)   
Stem cell dose median [range] CD34+ x 106/kg 3,96 (0,8-14) 0,9 (0,08-1,28)  
GvHD prophylaxis    
CSA+MMF 69 (100) 81 (100) ns 
Cy post transplant 69 (100)  
Days with ANC< 500 x 109/l 20 (14-39) 22 (6-67) ns 
Days with platelets<20 x 109/l 29 (14-50) 41 (18-80) ns 
Characteristic Total =150 patients Haplo transplant (n = 69) CB transplant (n = 81) P value 
Patients Age years (median) [range] 44 (19-68) 47 (18-66)  
Patients sex   ns 
Male 39 (57) 46 (57)  
Female 30 (43) 35 (43)  
Disease type    
AML 3 (4) 37 (46) <0.0001 
ALL 1 (1) 14 (17) <0.0001 
NHL 24 (35) 14 (17) ns 
HL 30 (43) 2 (2) <0.0001 
MM 4 (6) 2 (2) ns 
CLL 5 (7) 4 (5) ns 
CML 1 (1) ns 
MDS/ MPS 2 (3) 7 (9) ns 
Status of disease    
CR 37 (54) 56 (69) ns 
PR/SD 24 (35) 12 (15) 0.04 
PD 8 (11) 13 (16) ns 
Donor type    
Sibiling 32 (46)   
Parent 18 (26)   
Child 18 (26)   
cousin 1 (2)   
Donor/recipient sex mis-match 34 (49) 56 (69) ns 
ABO incompatibility 24 56 0.02 
Conditioning regimen    
Flu 5+Cy 1+ TBI 75 (93)  
Flu 5+Cy 2+ TBI 69 (100) 6 (7)  
Stem cell source    
Peripheral Blood 19 (28)   
Bone Marrow 50 (72)   
Stem cell dose median [range] CD34+ x 106/kg 3,96 (0,8-14) 0,9 (0,08-1,28)  
GvHD prophylaxis    
CSA+MMF 69 (100) 81 (100) ns 
Cy post transplant 69 (100)  
Days with ANC< 500 x 109/l 20 (14-39) 22 (6-67) ns 
Days with platelets<20 x 109/l 29 (14-50) 41 (18-80) ns 
Results

With a median follow-up of 59 months (8-101) and 18 months (3-51), in the UCB group versus the Haplo group, respectively. Nine patients (11%) in the UCB and 8 patients (12%) in the Haplo group had a spontaneous autologous reconstitution subsequent to primary graft failure. The median times to neutrophil and platelet recovery were 20 d (14–39) and 29 d (14–50) after Haplo and 22 d (6–67) and 41 d (18–80) after cord blood. All supportive care measures included red blood cell, and platelet transfusions were significantly increased in cord blood transplantation group. The cumulative incidence of transplant related mortality (TRM) at one year was 23% in the UCB group versus 17% in the Haplo group (P=0.39). Grade 2-4 acute graft-vs.-host disease (GVHD) and extensive chronic GVHD incidences were 52% versus 29% (P=0.05), and 12% versus 6% (P<0.0001), in the UCB group versus the Haplo group, respectively. The Kaplan-Meier estimate of overall survival at 2 years was 45% (95%CI, 34-56%) in the UCB group versus 69% (95%CI, 58-80%) in the Haplo group, (P=0.10). The estimate of progression-free survival at 2 years was 36% (95%CI, 25-47%) in the UCB group versus 65% (95% CI, 53-77%) in the Haplo group (P=0.01). Figure 1

Conclusion

In this study, relapse and PFS was lower in Haplo group than in UCB transplants. The main difference between the 2 groups was the significantly higher incidence of acute and chronic GVHD in the UCB group. Surprisingly, this did not translate into a decrease of the cumulative incidence of OS nor increase of the TRM, which may be explained by a slightly shorter follow-up in this group. Our results suggest that haploidentical transplants are a good and promising alternative option for patients with high risk hematological diseases who lack an HLA-matched donor (sibling or unrelated donor). This should be now investigated in prospective comparative studies.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.

Sign in via your Institution