Is it necessary to treat patients after syngeneic bone marrow transplantation?
Lidia S. Lubimova, Larisa A. Kuzmina, Elena N. Parovichnikova, Inna V. Alexeeva, Valeriy G. Savchenko
Hematologic Scientific Centre, Russian Academy of Medical Sciences, Moscow, Russia
Summary
Aim
To analyze the results of SyBMT in patients (pts) with leukemia.
Materials and methods
We included 11 pts: 7 CML (6 – CP, 1 – AP) and 4 AL (3 in CR, 1 in relapse): M/F 7/4, average age 24.5 years (13–39). In all cases myeloablative conditioning (BU 16 mg/kg+Cph 120 mg/kg) was used. Morphological, cytogenetic and molecular (FISH, RT PCR) investigations were performed.
Results
Of the 7 CML pts, 4 are alive: 2 have been in complete molecular remission (CMR) for 143 and 206 mo, while a third has been in complete cytogenetic remission (CCR) for 17 mo. During the first 3 mo after BMT, the third patient had a very weak expression of the BCR/ABL gene according to an RT PCR. In 6 mo he was negative according to an RT PCR and in 13 and 16 mo BCR/ABL was determined again (0.05–0.04%) accordingly. One pt with AP CML has been in a chronic phase for 136 mo, while 3 pts relapsed and died. Of the 4 pts with AL, 3 are alive – all 3 were in CR before BMT. One pt remained in CMR and 2 pts achieved only CCR, but the persistence of inv (16) – which was detected before BMTaccording to an RT PCR – was revealed. Therefore, of the initial 11 pts, 7 (64%) are alive: 6 of who are in CCR – of which 3 are in CMR. At the same time, 3 pts with CCR – 1 CML and 2 AL – have MRD according to an RT PCR; FISH was negative in all cases.
Conclusion
After SyBMT, long survival of pts is possible in the majority of cases where CCR has been achieved. The RT PCR method was the most informative for the diagnosis of MRD, which was recognized in 3 of the 6 pts. We previously published our first encouraging results of using immunomodulatory therapy after autological BMT: the relapse rate decreased twice in treated pts. At that time a question came up: Is it necessary to treat patients after SyBMT, especially those with MRD? Recently, the use of immunomodulatory therapy after SyBMT was initiated in our clinic: IFN-α in CML and IFN-α + ATRA or IL2 in acute AL. The results will be evaluated in the future.
Keywords
syngeneic bone marrow transplantation, graft-versus-leukemia effects, GVL, acute leukemia, AL, chronic myeloid leukemia, CML, minimal residual disease, MRD