Graft-Failure After Allogeneic Stem Cell Transplantation. Outcome and Prognostic Factors in 80 Patients

Graft-failure (GF) is an infrequent and poor complication of allogeneic stem cell transplantation (SCT). Strategies for reversing GF will depend on the options available in each situation.

A questionnaire about GF was sent to all centers of the Grupo Español de Trasplante Hematopoyético (GETH). Fourteen Spanish institutions reported their GF from January 2006 to October 2010. Primary GF was defined as ANC >0.5×10⁹/L not reached for three consecutive days by day +28 after SCT from peripheral blood (PB) or bone marrow (BM) progenitors and by day +60 after SCT from unrelated cord blood (UCB) progenitors. Secondary GF was defined as a recurrent ANC <0.5×10⁹/L for at least 7days.

Eighty patients with GF were reported (median age 34 yr. [range: 1–68]; 54M/26F). Basal diseases were AML 30 (38%), ALL 14 (17%), lymphoproliferative disorder 12 (15%), myelodysplastic syndromes 9 (11%), myeloproliferative syndromes 7 (9%), aplastic anemia 5 (6%), and congenital disorders 3 (4%). Status of the neoplastic disease was: 1^st/2^nd CR or 1^st chronic phase in 50 (62%) patients and >2^nd CR or active disease in 30 (38%) patients. Conditioning therapy for 1^st SCT was myeloablative in 45 (56%) and non-myeloablative in 35 (44%) patients. Donors were related in 35 (44%) and unrelated in 45 (56%). Progenitors were from mobilized PB in 45 (56%), UCB in 26 (33%) and BM in 9 (11%). At the time of GF, chimerism status (n=75) was donor complete in 6 (8%), mixed in 28 (35%) and from the patient in 41 (55%) individuals. Forty-five (56%) and 35 (44%) patients presented primary and secondary GF.

Seventy-one patients received a second SCT from the same donor (31 patients [44%]), from a different donor (35 patients [49%]) or an autologous back-up (5 patients [7%]). The most frequent conditioning regimens (n=65) in second allogeneic stem cell infusion were fludarabine+ thymoglobulin (ATG) (19 [29%]), anti-lymphocyte immunoglobulin alone (9 [14%]) and cyclophosphamide+ATG (6 [9%]). ATG or alemtuzumab were used in 52 patients (80%) as part of the preparative regimen. Progenitors were from mobilized PB in 52 (79%), UCB in 8 (12%) and BM in 6 (9%) patients. Eleven (20%) and 2 (4%) out of 55 evaluable patients presented again primary or secondary GF.

The median survival time from GF was 12 months [range: 1–23].The 5-yr. probability of survival was 28% (95%CI: 14%–42%) with a median follow-up for alive patients of 27 months [range: 1–103]. The 5-yr. non-relapse mortality was 47% [35%–59%]. There was a trend for a better survival in patients under 18 years-old. No other factors such as graft source, in vivo T-cell depletion or the conditioning regimen influenced on patient's survival. By competing risk estimation, the transplant-related mortality and the relapse probability at 5 years in the 66 patients that received a second transplant were 51% [95%CI: 38% – 63%] and 24% [95%CI: 10% – 41%].

The prognosis of GF after allogeneic SCT was poor, although some patients presented long survival if successful recovery of GF was obtained. The strategy adopted to treat GF has been heterogeneous. Younger age showed a trend for better survival in this series. Supported by grants P-EF/10 from FIJC and RD06/0020/1056 from RETICC.

Sanz:Novartis: Speakers Bureau.