Longer Follow-Up Confirms a Low Relapse Rate after Non-Myeloablative Allogeneic Transplantation (NMT) for Non-Hodgkin's Lymphoma (NHL), Including Patients with PET or Gallium-Avid Disease.

Abstract

We have used the combination of fludarabine/cyclophosphamide/rituximab (FCR) as a conditioning regimen for NMT in patients (pts) with relapsed NHL (Blood 989:3595, 2001). Seventy-eight consecutive pts were treated. Median age was 53 yrs (range, 21–68). Median # of prior chemoregimens was 3. Twenty-one (27%) had failed a prior autologous. Histologies included follicular (FL)=47 pts (60%), diffuse large cell (DLCL)=16 pts (21%) and mantle cell (MCL)=15 pts (19%). Thirty-nine (50%) were in partial remission (PR), five (6%) had stable or progressive disease (SPD) and 34 (44%) were in complete remission (CR) at study entry. Sixty-nine (88%) had a matched sibling, 6 a matched unrelated, and three a mismatched sibling donor. Ten pts had either PET or Gallium-avid disease at transplant: six were in clinical PR and 4 were in SPD. Peripheral blood was the source of graft in 71 pts (91%). Tacrolimus/Methotrexate were used for GVHD prophylaxis. Median time for ANC >500 was 10 days. Sixty pts did not require any platelet transfusion. All but 2 pts who had SPD, converted to CR post transplant. All pts engrafted donor cells. Six had a secondary graft failure (GF), two of which occurred in the setting of disease progression. With a median follow-up time of 34 months (mos) (range, 3 to 70 mos), only 6 pts (8%) relapsed: two pts were in SPD/PET or Gallium(+), 3 were in PR/PET or Gallium(−) and one was in CR at transplant. None of the 6 pts who were PR/PET or Gallium (+) at study entry relapsed. Overall the risk of relapse in PET/Gallium (+) or (−) disease was not significant (P=0.15). Five pts received donor lymphocyte infusion (DLI) for disease progression: one achieved CR; the 4 other pts (two were in GF) did not respond. DLI was also given successfully to two other pts because of cytopenia related to a viral infection (1), and because of decreasing chimerism (1). Overall survival (OS) for all pts was 88%, 82% and 74% at 1,2 and 3-yr, respectively. By univariate analysis, OS was 95% at 3-yr for those who had failed a prior autologous transplant (P = 0.04). Patients with FL histology had also a better 3-yr survival than DLCL [88 % vs 51% (P = 0.008)]; the difference with MCL (65% at 3-yr) was not statistically significant (P = 0.2). Non-relapse related mortality was 11%, 13%, and 19% at 1, 2 and 3-yr, respectively. The incidence of acute II-IV GVHD was 17%. Patients with FL disease had lower incidence of acute II-IV and III-IV GVHD than DLCL [11% vs 31%, P = 0.04; and 2% vs 25%, P = 0.02; respectively] which may have contributed to the higher OS rate in FL. Both FL and DLCL pts had similar age and donor type distribution. Two pts developed chronic GVHD post DLI. The incidence of chronic extensive and limited GVHD was 51% and was not statistically different between various histologies. We conclude that NMT with FCR for NHL is an effective treatment even in pts who failed a prior autologous transplantation and is associated with a low incidence of acute GVHD. The lower than expected relapse rate observed may be indicative that NMT could be curative for these diseases.