Abstract 3028

Objective:

Methotrexate (MTX) is widely used as prophylactic for GvHD. We retrospectively evaluated all CBT, to determine if there is any correlation between transplant outcomes and short course MTX prophylaxis.

Patients & Method:

Between January 1995 and January 2011, 142 CBT were performed at CMH for the treatment of malignant or non-malignant conditions on IRB approved protocols. Cord blood units were processed as described by Rubenstein et al. GvHD prophylaxis was either Methotrexate (MTX) with anti-thymocyte globulin (ATG) and cyclosporine A (CSA) in 91patients; or non MTX regimens with/without ATG and CSA, in 51 patients. Statistical analysis for group and sub groups were done using Fisher's exact and log-rank tests, column statistics and unpaired t test. Significance was determined at the p-value of 0.05. Median ± SEM were also calculated and all have a confidence interval at 95%. There were 64 female and 78 male recipients; with 76 female and 65 male CBT units. Median age and weight at transplant were 3.7 yrs (0.1 – 20.6) and 20.1 kg (3.0- 73). Degree of HLA matching was 6/6 (n= 15), 5/6 (n= 35), 4/6 (n= 83), 3/6 (n= 8). 8 cord blood units were from related donors (MR), 134 were from unrelated donors (MUD). 58 patients (41%) had ABO mismatch. HLA matching, ABO group and donor sex was not available for 1 patient-donor pair. The median cell dose was 0.90 × 108/kg TNC, 0.79 × 108/kg MNC and 1.14x 106/kg CD34+ cells, (0.09– 4.27; 0.08– 3.84; 0.02– 8.7 respectively). Malignant diagnoses (n= 95) (ALL (n= 47), AML (n= 29), MDS (n= 8), other (n= 11)); non-malignant (n= 47) (x-linked diseases (n= 21), Anemias (n= 9), Hemophagocytosis (n= 6), Osteopetrosis (n= 5), other (n= 6)). 130 patients (92%) received ablative regimens of fTBI + VP, Cy, TT or Bu, Cy + VP or TT, Cy + FLUD; 12 patients (8%) received non-ablative regimens of VP, Cy, or FLUD + Bu, Cy.

Results:

An ANC of >500 cells/μL was achieved in 78% of patients at 23 days (14– 60); 75% achieved PLT count of >20, 000 at 43 days (14– 105); and 65% achieved >95% donor cell chimerism at median of 28 days (13– 169). 32 patients (22.5%) died within day +100 from TRM. 17 patients (18%) had relapse at median of 153 days (34– 720). Acute GvHD was seen in 45.8% patients and 5.6% developed chronic GvHD. EFS at 1, 3 and 5 yr was 52%, 50% and 50% respectively, with 1, 3 and 5 yr OS of 63%, 60% and 60%. 62 patients are survivors. Median follow up was for 3 yrs (0.1- 16.4 yr). Outcomes for the MTX and non-MTX groups were as in Table 1.

Table 1
Whole group, n= 142MTX, n= 91Non-MTX, n= 51p-value
Malignancy (n, %) 95, (66.9%) 74, (81.3%) 21, (41.2%) <0.0001 
Non-malignancy (n, %) 47, (33.1%) 17, (18.7%) 30, (58.8%)  
fTBI regimen (n, %) 95, (66.9%) 72, (79.1%) 23, (45.1%) <0.0001 
Non-TBI regimen (n, %) 47, (33.1%) 19, (20.9%) 28, (54.9%)  
ANC >500 (n, %) 99, (78%) 69, (75.8%) 30, (58.8%) 0.73 
Median Days to ANC >500 23 25 20 0.008 
ANC >500 at 30 & 45 days 49%, 76% 52%, 78% 52%, 70%  
PLT >20,000 (n, %) 93, (75%) 65, (71.4%) 28, (54.9%) 0.52 
Median Days to PLT >20,000 43 44 42 0.41 
PLT >20,000 at 30, 45 & 100 days 16%, 45%, 88% 16%, 44%, 91% 15%, 47%, 79%  
Chimerism (n, %) 92, (64.8%) 63, (69.2%) 29, (56.9%) 0.23 
Median Days to chimerism 28 30 25 0.26 
TRM (n, %) 32, (22.5%) 19, (20.9%) 13, (25.5%) 0.55 
Relapse (malignant group only) (n, %,median days) 17/95, (18%), 153 days 12/74, (16.2%), 214 days 5/21, (23.8%), 57 days 0.51 
EFS (n, % No events); (1yr, 3yr, 5yr %) 69, (49%); (52%, 50%, 50%) 46, (51%); (54%, 54%, 54%) 23, (45%); (51%, 46%, 46%) 0.27 
OS (n, % alive); (1yr, 3yr, 5yr %) 83, (58%); (63%, 60%, 60%) 52, (57%); (62%, 58%, 58%) 31, (61%); (63%, 63%, 63%) 0.91 
Acute GvHD (n, %) 65, (45.8%) 46, (50.5%) 19, (37.3%) 0.16 
Chronic GvHD (n, %) 8, (5.6%) 6, (6.6%) 2, (3.9%) 0.71 
Whole group, n= 142MTX, n= 91Non-MTX, n= 51p-value
Malignancy (n, %) 95, (66.9%) 74, (81.3%) 21, (41.2%) <0.0001 
Non-malignancy (n, %) 47, (33.1%) 17, (18.7%) 30, (58.8%)  
fTBI regimen (n, %) 95, (66.9%) 72, (79.1%) 23, (45.1%) <0.0001 
Non-TBI regimen (n, %) 47, (33.1%) 19, (20.9%) 28, (54.9%)  
ANC >500 (n, %) 99, (78%) 69, (75.8%) 30, (58.8%) 0.73 
Median Days to ANC >500 23 25 20 0.008 
ANC >500 at 30 & 45 days 49%, 76% 52%, 78% 52%, 70%  
PLT >20,000 (n, %) 93, (75%) 65, (71.4%) 28, (54.9%) 0.52 
Median Days to PLT >20,000 43 44 42 0.41 
PLT >20,000 at 30, 45 & 100 days 16%, 45%, 88% 16%, 44%, 91% 15%, 47%, 79%  
Chimerism (n, %) 92, (64.8%) 63, (69.2%) 29, (56.9%) 0.23 
Median Days to chimerism 28 30 25 0.26 
TRM (n, %) 32, (22.5%) 19, (20.9%) 13, (25.5%) 0.55 
Relapse (malignant group only) (n, %,median days) 17/95, (18%), 153 days 12/74, (16.2%), 214 days 5/21, (23.8%), 57 days 0.51 
EFS (n, % No events); (1yr, 3yr, 5yr %) 69, (49%); (52%, 50%, 50%) 46, (51%); (54%, 54%, 54%) 23, (45%); (51%, 46%, 46%) 0.27 
OS (n, % alive); (1yr, 3yr, 5yr %) 83, (58%); (63%, 60%, 60%) 52, (57%); (62%, 58%, 58%) 31, (61%); (63%, 63%, 63%) 0.91 
Acute GvHD (n, %) 65, (45.8%) 46, (50.5%) 19, (37.3%) 0.16 
Chronic GvHD (n, %) 8, (5.6%) 6, (6.6%) 2, (3.9%) 0.71 
View Large
Conclusion:

In this cohort the number of patients with malignant disorders who received fTBI regimen was statistically significantly higher in the MTX group. Patients in the MTX group took longer to ANC engraftment. There was no other statistical significance between the MTX and non-MTX groups with respect to TRM, Engraftment, GvHD, OS or EFS. In conclusion, short course MTX prophylaxis does not influence transplant outcomes in pediatric CBT for malignant or non-malignant conditions.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
child, cognitive-behavioral therapy, engraftment, graft-versus-host disease, host (organism), methotrexate, pediatrics, tissue transplants, transplantation, umbilical cord blood transplantation

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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