Punit Jain, Lalchand (2014) Evaluation of Berlin-Frankfurt-Munster (BFM)protocols in Acute Lymphoblastic Leukemia and the role of Flow Cytometry in Minimal Residual Disease Monitoring: A Single Tertiary Centre Analysis from India. Masters thesis, Christian Medical College, Vellore.
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Abstract
INTRODUCTION : Acute lymphoblastic leukemia (ALL) is a malignant disease of immature lymphoid cells proliferating at an uncontrolled rate with a block in its early stage of differentiation.(1) It has been reported as one of the most common malignancy of the childhood, accounting for almost 25% of all pediatric tumours and about 80% of pediatric leukemia.(1,2) Its incidence shows a bimodal peak, with the initial and the highest peak seen between 2 to 5 years of age and then a continues decline in the incidence with increasing age till the age of 50 years, following which it again shows a second peak. AIMS AND OBJECTIVES : (1) To study the clinical profile of children and adults diagnosed with acute lymphoblastic leukemia in our institute and their treatment outcome, when treated with different BFM protocols. (2) To evaluate the clinical outcome in adolescent patients with acute lymphoblastic leukemia between 15 - 20 years of age, by using pediatric treatment regimens instead of adult regimens as currently used. (3) To assess the role of minimal residual disease status monitoring by flow cytometry at time of documenting remission, post induction phase of chemotherapy. METHODOLOGY : For retrospective analysis of adult patients, we included all newly diagnosed patients with acute lymphoblastic leukemia from January 2004 to February 2014. For adolescent patients, we compared adolescents treated by adult regimens from January 2004 to June 2012 with those adolescents treated with pediatric regimens from July 2012 to February 2014. We also compared standard and intermediate risk pediatric patients treated with the non BFM 95 regimens from January 2004 to those receiving BFM 95 based regimens from 2008. Lastly, since July 2012 we prospectively analyzed the role of flow cytometry in assessing the minimal residual status at the end of induction chemotherapy and compared the outcomes of those who tested positive with those tested negative. RESULTS : Among 455 adults analyzed, there were 331(72.7 %) standard risk and 124 (27.2 %) high risk adults. Median follow up duration was 65 months. There were 132 (29 %) relapses and 179 (39.3 %) deaths. The 5 year EFS was 50.1 ± 2.9 % and the 5- year OS was 51.6 ± 2.9 %. Among children with standard risk ALL, with an actuarial median follow up period of 25(1.5 - 65) months and 17(1- 64) months for those treated with the BFM 95 protocol and those with the Non MTx/Non RT based study protocol; the three year event free survival was 95 ± 4.9 % and 86.5 ± 6.5 % respectively. (P value= 0.391). Among children with intermediate risk ALL, with an actuarial median follow up period of 27 (1 - 47) months and 18 (1-116) months for those treated with the BFM 95 protocol and those with the radiation (RT) based protocol; the two year overall survival was 96.9 ± 3.1 % and 85.6 ± 2.4 % respectively. (P value = 0.103) With an actuarial median follow up period of 7.7 (1 - 19) months and 18(1-118) months those treated with intermediate risk pediatric protocol and the modified adult GMALL protocol; the one year event free survival was 82.3 ± 7.3 % and 75.9 ± 3.6 % respectively.(P value = 0.752) Among patients tested for the minimal residual disease, with an actuarial median follow up of 7.7 (1-19) months, the 6 months and 1 year EFS in MRD (-) cohort (n = 53) is 97.4 ± 2.6 %. With an actuarial median follow up of 7.7 (1-13) months, the 6 months and 1 year EFS in MRD (+) cohort (n = 16) is 75 ± 21.7 %. With a median follow up of 6 months, the 6 months OS in MRD strongly (+) cohort (n = 6) is 20 ± 17.9 %. (P = 0.000) CONCLUSION: Using the current modified GMALL and BFM 95 regimens in adults (≥ 15 years) and children (>1<15 years), treatment outcomes were comparable to those reported in the international literature. There was no significant difference as yet in the BFM 95 and the non BFM 95 regimens. Using pediatric regimens in adolescent age group (≥15 ≤ 20 years) did not reveal any significant difference in overall outcome as compared to adult regimens. Though the follow up is short, pediatric regimens are feasible in adolescents with minimal toxicity and there appears to be a trend towards improvement in their outcomes with pediatric regimens. Using flow cytometry in detecting minimal residual disease can significantly identify high risk patients and improve their outcome by timely intensification.
| Item Type: | Thesis (Masters) |
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| Uncontrolled Keywords: | German Multicentre study group for Adult ALL (GMALL) ; Berlin-Frankfurt-Munster Protocols ; Acute Lymphoblastic Leukemia ; Flow Cytometry ; Minimal Residual Disease Monitoring ; Single Tertiary Centre Analysis. |
| Subjects: | MEDICAL > Clinical Haematology |
| Depositing User: | Subramani R |
| Date Deposited: | 16 Aug 2017 00:39 |
| Last Modified: | 16 Aug 2017 03:36 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/1790 |
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