173 Lower Lymphocyte Count At Day 30 Predicts Worse Overall Survival with Tacrolimus and Mycophenophelate Mofetil Use for Gvhd Prophylaxis: A Large Retrospective Analysis

Track: Contributed Abstracts
Wednesday, February 13, 2013, 6:45 PM-7:45 PM
Hall 1 (Salt Palace Convention Center)
Zaid Al-Kadhimi, MD , Karmanos Cancer Center/ Wayne State University, Detroit, MI
Zartash Gul, MD , Hematology/BMT, University of Kentucky/Markey Cancer Center, lexington, KY
Emily Van Meter, PhD , College of Public Health, University of Kentucky, Lexington, KY
Muneer H. Abidi, MD , Internal Medicine- Bone Marrow Transplant, Wayne State University/Karmanos Cancer Center, Detroit, MI
Abhinav Deol, MD , Oncology, Wayne State University/Karmanos Cancer Institute, Detroit, MI
Lois Jeanne Ayash, MD , Karmanos Cancer Institute, Detroit, MI
Lawrence Lum, MD, DSc , Oncology, Karmanos Cancer Institute, Detroit, MI
Voravit Ratanatharathorn, MD , Bone Marrow Transplantation, Karmanos Cancer Institute, Detroit, MI
Joseph Uberti, MD , Bone Marrow Transplant, Karmanos Cancer Institute - Wayne State Univ, Detroit, MI

Higher absolute lymphocyte count at day 30  (ALC 30) after allogeniec hematopoietic stem cell transplant (HSCT) has been associated with better overall survival (OS).This has largely been evaluated in small retrospective studies with cyclosposrine and methotrexate for graft vs. host disease (GVHD) prophylaxis.  ALC 30 and its impact on patient (pt) outcomes after tacrolimus (Tac) and mycophenolate mofetil (MMF) is largely unknown.

We retrospectively evaluated a cohort of 414 consecutive pts between January 2005 and June 2010 at Karmanos Cancer Center.  Patients with GVHD or death before day 30 post transplant were excluded from the analysis (N =33). We performed a multivariate logistic regression analysis to determine donor/recipient predictors of ALC 30. Cox proportional hazard models were used to assess the impact of ALC 30 on the incidence of transplant outcomes listed in the table below.  All analyses were adjusted for donor/recipient age, sex, CMV status, HLA mismatch, CD34+ cells, regimen intensity and relapse risk.

There were 191 pts in the sibling donor (SD) group and 190 pts in the unrelated donor (UD) group respectively.  The median age of pts and donors in the SD group was older (p< 0.05). Pts in UD group received a higher median of CD 34+cell dose (7.31 vs.5.63 x 106/kg  p=<0.0001). Median follow up of surviving pts in both groups was 58.3 months.  More pts had ALC 30>400x 106 (75 vs. 65% P=0.025) and more pts survived (47 vs.36%P=0.038) in the SD group. Factors associated with lower ALC 30 were:  higher donor age, HLA mismatch, lower recipient age, and lower CD34 cell dose.   

Lower ALC 30 (≤400x 106/L) was associated with lower OS, and increased non relapse mortality (NRM) for the whole cohort as well as for the SD and UD groups separately. Lower ALC 30 was associated with more severe aGVHD (III-IV) in the UD group. Lower ALC 30 was associated with more CMV reactivation and a trend towards more aGVHD  in the SD group.  

Conclusion

In this large retrospective study using Tac/MMF for GVHD prophylaxis ALC 30 ≤400 x 106/L was associated with worse OS, increased NRM and aGVHD.

Hazard Ratios of ALC 30 with various event outcomes

Combined

Related

Unrelated

Mortality           HR

                         CI

2.29***

1.68-3.13

2.58***

1.61-4.13

2.23**

1.44-3.46

NRM                 HR

                         CI

3.03***

2.08-4.43

3.19***

1.75-5.80

3.1***

1.84-5.23

aGVHD (II-IV)  HR  

                         CI

1.47*

1.06-2.03

1.64

0.99-2.72

1.43

0.9-2.28

aGVHD (III-IV)  HR

                          CI

1.97**

1.31-2.97

1.9

0.96-3.75

2.19**

1.27-3.77

cGVHD             HR

                         CI

1.01

0.7-1.45

0.83

0.47-1.47

1.02

0.62-1.69

CMV                 HR

                         CI

1.13

0.71-1.81

1.99*

1.05-3.75

0.6

0.27-1.29

Relapse            HR

                         CI

1.196

0.69-2.06

1.4

0.65-2.99

1.03

0.45-2.34

*p-value<0.05

**p-value<0.01

***p-value<0.001