Incidence and Pattern of Graft-Versus-Host Disease in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation After Non-Myeloablative Conditioning with Total Lymphoid Irradiation and Antithymocyte Globulin

Non-myeloablative (NMA) conditioning with total lymphoid irradiation and antithymocyte globulin (TLI/ATG) has been shown to protect against acute graft-versus-host disease (GVHD), while preserving graft-versus-malignancy effects. Reported here is our institutional experience with allogeneic hematopoietic cell transplantation (allo-HCT) following TLI/ATG conditioning. Criteria used to select TLI/ATG conditioning included; age ≥65 and/or HCT-CI of >3.  Patients received ATG (1.5 mg/kg/day) from day -11 through -7 and a total dose of 8Gy of TLI administered from day -11 through -1 followed by cell infusion of day 0. GVHD prophylaxis consisted of combination of either cyclosporine/mycophenolate mofetil (MMF) or tacrolimus/MMF in those undergoing a matched sibling or unrelated donor allo-HCT, respectively. Table 1 summarizes the baseline patient characteristics (n=20). The median follow up for surviving patients is 723 days (range 180-1364 days). All patients engrafted, except one who experienced primary engraftment failure. The median time to neutrophil engraftment was 16 days (range 9-23 days) and platelet engraftment was 10 days (range 6-24 days). Median donor chimerism on days +30, +100 and +365 was 93% (range 60-100%), 95% (range 54-100%), and 100% (range 56-100%) respectively. Cumulative incidence (CI) of grade II-IV acute GVDH while accounting for competing events, at day +100 was 34.2% (n=6) and 46.2% (n=8) at day +180. The CI for grade III-IV acute GVHD was 22% (n=4) at day +100, and 29.4% (n=5) at day +180. CI of chronic GVHD (cGVHD) was 50.5% at one year. CI of limited and extensive chronic GVHD was 22.1% (n=3) and 29.2% (n=4), respectively at one year. The CI of relapse was 11.7% (n=2) at one year. The non-relapse mortality (NRM) was 0% at day +100 and 14.7% (n=2) at one year. Causes of death include disease relapse (n=2), GVHD (n=2), and accident (n=1). The overall and progression free survival at one year is 73.5%. Our limited, retrospective data show encouraging relapse and NRM rates with TLI/ATG-based NMA conditioning, but with higher than previously reported rates of acute and chronic GVHD, underscoring the need for novel strategies designed to effectively prevent GVHD.

Table 1.

Characteristics	N=20
Median age; years (range)	59 (26-72)
Male (%)	13 (65%)
Diagnosis, no. (%)
Acute Myeloid Leukemia	4 (20%)
Non-Hodgkin Lymphoma	11 (55%)
Chronic Leukemia (CLL or CML)	4 (20%)
Hemophagocytic syndrome	1 (5%)
Disease risk, no. (%)
High risk	5
Intermediate risk	10
Low risk	4
Prior autografting, no. (%)
Yes	1 (5%)
No	19 (95%)
Donors, no. (%)
Related	5 (25%)
Unrelated	15 (75%)
Sex mismatch, no (%)
M to M	9 (45%)
M to F	3 (15%)
F to M	4 (20%)
F to F	4 (20%)
Degree of HLA match, no. (%)
10/10	19 (95%)
9/10	1 (5%)
Median KPS; (range)	80 (70-100)
Median HCT-CI; (range)	1 (0-5)
Median CD34 cell dose†  (106 cells/kg recipient body weight), (range)	5.7 (1.5-11.3)