Taperring Treatment According Minimal Residual Disease

In spite its established prognostic role in ALL and being a powerful method for patient stratification, Minimal residual disease in AML is still an area of research need to be investigated to decide its value in AML treatment.

In this is a retrospective study, 388 adult AML patients from period 2009-2014 in NCI Cairo University were included, comparing minimal residual disease to other prognostic factors to determine its value as an independent prognostic factor to stratify AML patients and to assess possibility of treatment tapering according MRD.

We divided patients in to 3 groups according cytogenetics: favorable, intermediate, poor risk.

(We considered patients having negative MRD: those having day 28 and day 42 BMA free for MRD less than 0.01)

All patients with FLT3 were excluded prior start this study because we proved by other study its grave prognosis and it outweigh MRD as independent prognostic factor, and eventually those patients will relapse within a short period of time.

5 years disease free survival

First group patient with favorable cytogenetics: included 156 patients. We found that 76 patients who become MRD negative post first cycle induction had significantly better disease free survival 64% and overall survival 61.7% compared to those having persistence MRD ( 80 patient) post first cycle of induction 24%, 14% respectively with p value 0.02.

Out of 76 patients had negative MRD, 29 patients just took 2 cycles of chemotherapy one induction chemotherapy and one consolidation. Those patients continued to maintain CR in spite receiving 2 cycles of chemotherapy which confirm powerful prognostic impact of MRD with DFS : 61, OS 59.3% which showed no significant difference from those who completed their chemotherapy (p value : 0.07)

Those patients didn't continue treatment due to medical problems or non compliance or insurance coverage problems.

Those who had persistence MRD post first cycle of induction had prognosis resembling those of poor cytogenetics. Out of 80 patients having persistent MRD, 9 died prior relapse due to medical problems. 64 relapsed and took salvage chemotherapy then kept under follow up. 23 patient did allogenic bone marrow transplantation, 9 were in CR and were done due to persistence MRD and 14 patient did due to relapse and transplantation were done in second CR. patients who had did allogenic transplantation had better disease free survival and overall survival.

Second group intermediate risk: 103 patients. We had 40 patients with negative MRD, whose DFS and OS were 59% and 55% respectively. Of those patients, 14 received only 2 cycles of chemotherapy and also showed favorable prognosis in spite being intermediate risk and retained CR. DFS : 57%, OS 55% with no statistical difference between those continued chemotherapy or not.

63 Patients had positive MRD, out of them 5 patients had lost follow up. DFS was13% and OS was 11%. 47 patients relapsed took salvage chemotherapy and kept under follow up out of which 16 patients did bone marrow transplantation. 11 patients did bone marrow transplantation due to persistence MRD and they had longer disease free survival compared to those had salvage chemotherapy and kept under follow up. Same disease free survival overall survival to those did BMT post second CR.

Third group with poor risk cytogenetic included 127 patients. 32 patients got MRD negative (DFS: 38% OS: 8%). Out of which 9 didn't receive further chemotherapy post 2 cycles. Again with no significant p value between both groups (P: 0.08)

We had 95 patients with persistent MRD post induction. 11 patients lost follow up.

65 relapsed and received salvage chemotherapy DFS 29% and OS: 5%. 19 patients did allogenic bone marrow transplantation. 8 patients did allogenic bone marrow transplantation due to persistence MRD.

We found that poor risk cytogenetic outweighs MRD and only patients did BMT had favorable outcome regarding disease free survival 42% and overall survival 11%.

Finally we conclude that minimal residual disease can be used as independent prognostic factor. Also MRD can be used as in stratifying patients and tailoring the treatment plan allowing the possibility to stop treatment at a less number of cycles and preventing further chemotherapy complications.