Increasing Chemotherapy Intensity Improves Relapse Rate and Not Overall Survival in AML Patients: A Single Center Experience

BACKGROUND

Acute Myeloid Leukemia (AML) represents 15%-20% of all leukemia in children less than 14 years. Over the last few years' treatment modification, intensification, introduction of new chemotherapeutic agents, targeted therapy and concomitant haematopoietic stem cell transplantation (HSCT) in high risk patients has improved overall survival in children with AML up to 50-60 %.

METHODOLOGY:

The aim of this single center retrospective study is to describe the clinic-pathological features and outcome of chemotherapy and HSCT in patients admitted with diagnosis of AML between 2005 and 2014 at King Faisal Specialist Hospital and Research Centre (KFSH&RC)-Jeddah, Saudi Arabia.

RESULTS:

A total of 32 acute myeloid leukemia patients was admitted and treated at our institute during this study periods. Out of them male were 18 (56.3%). Mean age of study population was 6.5 +/- 5 years.

Fever was the most common presenting complaints 32 (100%) followed by lymphadenopathy 31 (97%), pallor 30 (94%), hepato-splenomegally 29 (91%) and bleeding 19 (60%). Four patients have Down syndrome (12.5%) and CNS involvement were documented in 3 (9.4%). Regarding etiology majority of the patients have De Novo 30 (93.7%) and remaining 2 (96.3%) cases have MDS. Case distribution according to FAB classification was as follow M1 (n=1; 3.1%), M2 (n=7; 21.9%), M3 (n=4; 12.5%), M4 Eo (n=1; 3.1%), M5 (n=8; 25%), M6 (n=4; 12.5%), M7 (n=4; 12.5%), and no information (n=3; 9.4%). Cytogenetic were normal in most cases 18 (56.3%) and abnormal cytogenetic was recorded in remaining 14 (23.8%) cases. Out of, complex cytogenetic (n=2; 6.3%), FLT3/ITD (n=2; 6.3%), Monosomy 7 (n=3; 9.4%), t(15;17) in (n=4; 12.5%) and t(8;21) in (n=3; 9.4%). Risk group classification was as followed; High risk (n=10; 31.3%), Intermediate (n=10; 31.3%) and low risk (n=11; 34.4%) and not done in (n=1; 3.1%).

Case distribution according to the chemotherapy protocol used for treatment were POG 8498 protocol (n=15; 46.9%) and AAML 0531 protocol (n=13, 40.6%). Remaining 4 (n=4, 12.5%) patients with diagnosis of APL were treated with C9710 protocol. Complete remission after 2 cycle of induction chemotherapy was achieved in 23 (71.3%) cases, 6 (18.8%) cases experienced induction failure and another 3 (9.4%) patients expired during induction chemotherapy and/or lost to follow up. Fungal infection was observed in two cases (n=2; 6.3%), one had is documented Candida infection and this patients did not recover and expired.

Sixteen patients received allogeneic HSCT after chemotherapy (8 belongs to high risk, 6 intermediate risk and 2 low risk group), out of them 12 were in complete remission and 4 patients were not in remission at the time of transplantation. Out of 8 patients who belongs to high risk group 3 were relapsed and 1 expired and out of 6 patients who belongs to intermediate risk group, 3 were relapsed and 1 expired after HSCT.

Overall relapse rate in group of patients treated with AAML 0531 and POG 8497 were (n=6/28; 21.4%) with mean duration of relapse 26 +/- 27 months. Relapse rate in patients treated with AAML 0531 protocol was much lower than those who treated with POG 8497 protocol (15% vs 27%). Overall mortality rate was (n=8/32; 25%) mean timing of expiry from diagnosis is 37 +/- 32 months with mean duration of follow up is 48 +/- 6.5 months. Mortality rate in both group of patients who were treated with AAML 0531 protocol or POG 8497 protocol was comparable (31% vs 27%).

CONCLUSION:

We observed better event free survival in our patients treated with AAML 0531 protocol, however, the overall survival was comparable with patients treated with POG 8497 protocol. Further large scale, multicenter and long-term follow up study will be required to validate these findings.