Disease and Comorbidity Status Predict Outcome after Nonmyeloablative Allografting for Advanced Haematological Malignancies.
Authors: Sorasio R. , Giaccone L. , Carella A.M. , Guidi S. , Allione B. , Benedetti E. , Carnevale-Schianca F. , Peccatori F.A. , Raimomdi R. , Sorà F. , Mordini N. , Peccatori J. , Patriarca F. , Fiore F. , Baldi I. , Resta I. , Festuccia M. , Gallamini A. , Sica S. , Aglietta M. , Lewis A. , Fanin R. , Bosi A. , Boccadoro Mario , Bruno B. 
Published: October 2019

Abstract
Nonmyeloablative (NM) regimens extended the application of allogeneic transplantation (AT) to older and/or medically unfit patients ineligible for high-dose conditionings. Moreover, several patients are offered AT after failure of prior lines of therapy. We retrospectively evaluated 108 patients, median age 51 (16–67), with advanced or heavily pre-treated hematological cancers [19 acute myeloblastic (AML) and 1 lymphoblastic leukemia (ALL); 8 myelodysplastic syndrome (MDS); 9 chronic myeloid (CML) and 9 chronic lymphocitic leukemia; 3 myelofibrosis (MF); 48 myeloma beyond first line treatment; 8 Hodgkin’s and 8 non-Hodgkin’s lymphoma) who underwent NM-AT at 12 Italian transplant Centres. Median time between diagnosis and transplant was 20 months. Sixty-one% of patients had failed at least one prior line of therapy, including 36 refractory or relapsed patients after 1 or more autologous transplants. At allografting, 15 patients had disease at lower risk of relapse (AML and ALL in first complete remission (CR), MDS without blast excess, CML in first chronic phase, untreated MF). Forty-two patients had active disease. The comorbidity score was evaluated with an AT-specific comorbidity index (CI) as described by Sorror et al: 51 patients had CI=0, 42 CI=1–2 and 15 CI≥3. Patients were conditioned with fludarabine 90 mg/m2 and 2 Gy total body irradiation. GVHD prophylaxis consisted of cyclosporine and mycophenolate mophetile. Graft failure was observed in 1 patient and rejection after disease recurrence in 4. After a median follow-up of 28 months post-allografting, 58 (54%) had refractory/progressive disease and 36 (33%) were in CR, including 23 who were not in CR at transplant (p<0,001). Cumulative incidences of grade II–IV acute GVHD and extensive chronic GVHD were 35% and 60% respectively. Fourteen patients (13%) died of transplant-related causes (TRM) and 36 (33%) of disease progression (DRM). Two-year TRM was 12% and was higher in patients with CI≥3 (HR 2.84, p=0.08) whereas DRM was 31% and was significantly influenced by disease status at transplant (HR 0.37 for patients in partial (PR) or CR, p=0.003). Median event-free (EFS) and overall survivals (OS) were 11 (95% Cl: 8–15) and 35 months (95% Cl: 21–42) respectively. OS was significantly better in patients in remission (HR 0.44, p=0.004) and a trend for better OS was also observed in patients with CI<3 (HR 0.73, p=n.s.). By multivariate analysis, disease remission at transplant was associated with better OS and EFS (HR 0.39, p=0.001 and HR 0.41, p<0.001 respectively) and there was a trend for worse EFS in patients with CI≥3 (HR 1.88, p=0.08). Age, number of prior therapies and time between diagnosis and AT did not affect OS and EFS. In summary, though retrospective, this report confirms that disease-status and comorbidity scores predict transplant outcome. The use of AT specific comorbidity scores in prospective studies is imperative to select patients who most benefit from this procedure.