Treatment of chronic myeloid leukemia relapsing after allogeneic bone marrow transplantation: the case for giving interferon.

Higano et al have recently communicated their experience with interferon-a (IFN-a) treatment in 14 chronic myeloid leukemia (CML) patients with cytogenetic relapse after unmanipulated allogeneic bone marrow transplantation (BMT).1 Eighty percent of their patients obtained complete cytogenetic responses, and the authors suggest that the response to IFN-a may be related to tumor burden after having found a twofold difference in durable complete cytogenetic responses between the group with cytogenetic relapses and their previous experience using IFN-a in hematologic relapses (57% v 29%). Given the small size of the series, it would be interesting to see if these results are concordant with the published data on that topic. For that purpose, we have reviewed the data of 106 relapsing CML patients that have been previously reported in the literature, including 9 patients treated in our institution.1-9 Hematologic and cytogenetic relapses have been analyzed separately. The results are summarized in Tables 1 and 2. Since 1988, we have offered IFN-a as initial therapy for CML patients who relapse after BMT. Out of nine patients treated in our institution (seven with hematologic relapses and two with cytogenetic relapses) three patients have obtained complete cytogenetic responses (CGR) at 11, 15, and 51 months of IFN-a treatment. One of these patients lost the response after 16 months of continuous CGR, and the other two continue in CGR 33 and 98 months after having obtained it. The clinical evolution of the last patient has been previously described.10 Among these two patients, molecular remission with polymerase chain reaction (PCR) negativity has been obtained both in blood and bone marrow in the patient with the longest CGR, but RNA bcr-abl has been continuously present in the bone marrow of the other patient, whereas it has been undetectable in blood reverse transcription (RT)PCR sensitivity, 1025 cells). Six patients are alive with a median of 54 months after IFN (range, 6 to 113 months). Two of the not-responding patients have received donor lymphocyte infusions plus IFN-a. One of them obtained CGR and has extense chronic GVHD, and the other one has had grade III acute GVHD. The response has not yet been evaluated. Three patients have died, two because of transformation and one because of hepatic cyrrhosis. The literature review shows that 43 patients with isolated cytogenetic relapse have been reported (Table 1). Genetic responses have been obtained in 26 of them (58%), and they have been complete in 19 (43%). The time for obtaining CGR has been between 2 and 51 months. Duration of CGR has been quite prolonged, and several patients remained in CGR more than 5 years after having obtained it. The results have been poorer in patients with hematologic relapses (Table 2). Out of 63 patients treated in this disease status, genetic responses have been obtained in 46%, but CGR has been achieved in 18 (28%). Most responses occurred in the first year of treatment, but later CGR has been described. Complete genetic responses have been more frequently reported in patients with non–T-depleted BMT (Tables 1 and 2). Although a recent analysis of the French Group has not detected influence of type of GVHD prophylaxis on response to IFN,8 the rate of CGR was slightly higher in non–T-depleted grafts (7 out of 16 v 4 out of 17; J. Reiffers, personal communication, 1996). A European Bone Marrow Transplantation group survey has found that among patients with cytogenetic relapse, partial or complete disappearance of Ph-positive cells occurred in 40% of untreated patients and in 42% of those treated with IFN. However, the IFN group contained significantly more patients with T-deplete grafts (22 out of 24).11 This point merits further consideration. If response to IFN-a is influenced by the status of T repletion of the graft, it can be argued that IFN may exert its effect not only directly but also by its immune actions. We feel that these studies confirm those obtained by Higano et al and indicate that IFN-a can induce CGR in more than 40% of the patients with CML in isolated cytogenetic relapse. We think that the results using IFN-a as front-line therapy of relapsing CML after BMT warrant a randomized comparison with the use of donor lymphocyte infusions.