Duration of Immunosuppressive Therapy for Chronic Graft-vs.-Host Disease (cGVHD) Following Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation (HCT).
Authors: Rezvani Andrew R. , Leisenring Wendy , Martin Paul L. , Flowers Mary E.D. , Maloney David G. , Chauncey Thomas R. , Sandmaier Brenda M. , Storb Rainer F. 
Published: October 2019

BACKGROUND: Chronic GVHD is a major determinant of quality of life after allogeneic HCT. Systemic immunosuppressants (IS) are the mainstay of treatment for cGVHD. Patients (pts) with cGVHD after myeloablative HCT are able to discontinue IS at a median of 23 months after HCT (Stewart et al., Blood 2004 Dec 1;104[12]:3501–6). We examined the duration of treatment with IS in patients with cGVHD after non-myeloablative HCT.

METHODS: All pts who underwent non-myeloablative HCT at our institutions through 31 Dec 2003 were assessed for inclusion. Two hundred sixty-nine pts were alive and free of their underlying disease at day +84 after HCT; 138 of these (51%) began systemic IS for cGVHD, at a median of 112 days after HCT. We analyzed these 138 pts with cGVHD to determine duration of treatment with IS. Diagnoses are listed in Table 1. Sixty-eight pts received related allografts and 70 received unrelated allografts; median age at HCT was 53.3 years. The allograft source was granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells (G-PBMC) in 137 pts and bone marrow in 1 pt. Relapsed malignancy and death were considered competing risk events in the estimation of cumulative incidence of discontinuation of IS; follow-up was censored at the time of death, relapsed malignancy, or discontinuation of all systemic IS.

RESULTS: Thirty-seven pts (27%) had recurrent malignancy and 23/138 (16%) died without recurrent malignancy while on IS; 41/138 (30%) discontinued all systemic IS after resolution of cGVHD; and 37/138 (27%) were alive without malignancy at last follow-up (median 3.7 years after cGVHD diagnosis), but remained on IS for cGVHD. Five-year cumulative incidence estimates by outcome are listed in Table 2. Of pts alive and free of malignancy at 5 years after cGVHD diagnosis, 58% had discontinued IS. In pts who discontinued IS, the median time to discontinuation was 2.0 (range, 0.3 – 5.7) years (see Figure).

CONCLUSION: The median time to resolution of cGVHD and discontinuation of IS in this group is comparable to that reported after myeloablative HCT (24 months vs. 23 months), despite the older age of these pts (median age 53.3 years, vs. 39.5 years in myeloablative cohort) and the prevalence of G-PBMC allografts (>99%, vs. 20% in myeloablative cohort). In this older population with cGVHD after non-myeloablative allogeneic HCT, the majority of pts who remain alive and free of relapsed malignancy have resolution of cGVHD over time.

Table 1. Underlying diagnoses among pts with cGVHD Diagnosis No. of pts (%) AML 19 (14%) ALL 6 (4%) CML 6 (4%) CLL 11 (8%) MDS 14 (10%) HD 9 (6%) NHL 31 (22%) MM 32 (23%) MPD 1 (<1%) Waldenstrom’s 1 (<1%) Renal cell carcinoma 1 (<1%) Wilms’ tumor 1 (<1%) Immunodeficiency syndrome 6 (4%) Total 138 Table 2. Five-year cumulative incidences Outcome 5-year cumulative incidence % (95% CI) Relapsed malignancy/death 45 (36–54) Alive, malignancy-free, on IS 23 (15–33) Alive, malignancy-free, discontinued IS 32 (23–41) Figure Figure