Abstract 4551

Background:

Acute graft versus host disease continues to affect approximately 60% of patients undergoing UHSCT, with significant mortality and morbidity.

Methods:

We prospectively evaluated the efficacy of combining Thymo (4.5 mg/kg divided doses on days -1,-2, and -3), tacrolimus and sirolimus in preventing aGVHD. The cumulative incidence (CI) rate of grade II-IV aGVHD was calculated using death without grade II-IV aGVHD and relapse as competing risks (Cr). The Cr: for non relapse mortality (NRM) CI was death due to relapse, for relapse CI was death without relapse, for chronic GVHD CI was relapse & non relapse mortality without cGVHD. Kaplan-Meier method was used to calculate overall (OS) and progression free survival (PFS). The incidence of infections and other complications were reported with the Wilson's 95% Confidence Interval (in table below).

Results:

Between August 2008 and November of 2010, we enrolled 47 patients (pts) with median age of 50(20–70) years. The Median follow-up time is 23.6 months (18.8–27.9). There were 21 AML, 10 MDS, 4 ALL, 2 CML, 2 CMML, 1 CLL, 3 Myelofibrosis, 2 multiple myeloma, 2 NHL. Preparative regimens included Bu/Flu 30, Bu/Flu-TBI 10, VP16/TBI 3, R-BEAM 1, and Flu/MEL-TBI 3. All pts received peripheral blood stem cells mobilized with G-CSF. Median CD34+ dose was 7.31×10 6/kg (1.9–18.6). Median donor age was 32.6 (19.0–61.0) years. All patients received daily G-CSF starting day +6 till engraftment. Twenty two pts received 8/8 and 25 received 7/8 HLA matched grafts respectively. All patients' engrafted, with median day of 11 (9–15). Twenty deaths occurred throughout the whole follow up period, due to: relapse 6, aGVHD 4, cGVHD 2, sinusoidal obstruction syndrome (SOS) 2, bleeding 1, multi organ failure 2, sepsis 2 and pneumonia 1. Twelve patients experienced disease relapse. Fourteen patients had non-relapse mortality.

Twelve pts developed Grade II-IV aGVHD, 5 grade II, 4 grade III, and 3 grade IV. The CI rate for grade II-IV aGVHD at 200 days post transplant is 0.23.4% (12.4, 36.3); CI of NRM at day 1057 is 31.9% (18.4, 46.2). CI of relapse at day 1057 is 30.4% (15.2,47.1). CI of cGVHD at day 890 is 40.2(21.5, 58.2), with total of 16 cases: 8 mild, 7 moderate and one sever based on NIH consensus criteria. Median PFS is 17.7 months. PFS at 6 months is 63% and 54% at 1 year. Median OS has not been reached. OS at 6 months is 73%, and 65% at one year. The incidence of infections and other transplant related morbidities are shown in the table below. There were 2 cases of thrombotic thrombocytopenic purpura (TTP) before day 100. 16 CMV by PCR, 10 EBV by PCR, 9 HSV, 10 BK cystitis, 31 bacterial infections, 4 oral candidiasis, and 3 SOS.

Conclusion:

These early results suggest that the combination of Thymo, tacrolimus and sirolimus in pts undergoing UHSCT is well tolerated and is associated with a low rate and severity of acute GVHD.

Clinical OutcomeIncidenceConfidence Interval
CI Grade II-IV aGVHD 23.4 (12.4, 36.3) 
CI Non-relapse mortality 31.9 (18.4, 46.2) 
CI cGVHD 40.2 (21.5, 58.2) 
CI Relapse 30.4 (15.2, 47.1) 
TTP before day 100 4.26 (1.17, 14.25) 
CMV PCR 34.04 (22.17, 48.33) 
EBV PCR 21.28 (11.99, 34.90) 
HSV 19.15 (10.42, 32.54) 
BK cystitis 21.28 (11.99, 34.90) 
Bacterial Infections 65.96 (51.67, 77.83) 
Oral Candidiasis 8.51 (3.36, 19.93) 
SOS 6.38 (2.19, 17.16) 
Clinical OutcomeIncidenceConfidence Interval
CI Grade II-IV aGVHD 23.4 (12.4, 36.3) 
CI Non-relapse mortality 31.9 (18.4, 46.2) 
CI cGVHD 40.2 (21.5, 58.2) 
CI Relapse 30.4 (15.2, 47.1) 
TTP before day 100 4.26 (1.17, 14.25) 
CMV PCR 34.04 (22.17, 48.33) 
EBV PCR 21.28 (11.99, 34.90) 
HSV 19.15 (10.42, 32.54) 
BK cystitis 21.28 (11.99, 34.90) 
Bacterial Infections 65.96 (51.67, 77.83) 
Oral Candidiasis 8.51 (3.36, 19.93) 
SOS 6.38 (2.19, 17.16) 
Disclosures:

Al-Kadhimi:Genzyme Pharmaceuticals: Research Funding. Off Label Use: The use of thymoglobulin, Sirolimus and Tacrolimus in blood and marrow transplant. Lum:Transtarget Inc: Equity Ownership, Founder of Transtarget.

Author notes

*

Asterisk with author names denotes non-ASH members.

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