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Brief Summary
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Background Justification/Relevance of the Proposed Work: - The established treatment protocol for AML involves the use of induction and 2-3 cycles of consolidation chemotherapy. Consolidation therapy is commonly achieved with high dose cytarabine in doses of 1.5-3 gm/m2 given twice a day, 12 hours apart on days 1, 3 and 5 of a cycle. This high dose of the drug is supposed to kill leukemic blasts including those normally shielded within the bone marrow microenvironment or sanctuary sites like the CNS. The flip side to this approach, is near ablation of the bone marrow, profound cytopenias and the risk of mortality during this phase till reconstitution of the marrow with hematologic recovery. Using the 1, 3, 5 schedule, the total duration of myelosuppression is prolonged leading to increased incidence of the above mentioned adverse effects. We hypothesize that by condensing the dosing schedule to days 1, 2 and 3, the total duration of myelosuppression will reduce, leading to a reduction in the duration of the neutropenic phase, thereby decreasing the morbidity and mortality. Besides, supportive care in the form of transfusion support, IV antibiotics, growth factors, duration of hospital stay and finally the cost of therapy (measured indirectly) will proportionately be less as compared to the conventional schedule. What needs to be evaluated is whether the use of the condensed schedule has equal efficacy in terms of overall response and relapse rates when compared to the conventional schedule. Also, by using high dose cytarabine in a condensed manner, we would like to ascertain whether the patients experience any form of immediate/infusion-related toxicity. The German AML study group have done the study and they have found positive results. However, it has not been done elsewhere, including India. If we see similar results, this study will go a long way in devising AML treatment guidelines for our resource-constrained country. Hypothesis of the study: By condensing the dosing schedule to days 1, 2 and 3, instead of the standard 1, 3 and 5-day therapy, the total duration of myelosuppression will reduce, leading to the reduction in the duration of the neutropenic phase, thereby decreasing the morbidity and mortality. Also, supportive care in the form of transfusion support, IV antibiotics, growth factors, duration of hospital stay and finally the cost of therapy (measured indirectly) will proportionately be less as compared to the conventional schedule.
Aim of the study: To compare the conventional schedule of HiDAC consolidation chemotherapy [Cytarabine given as an IV infusion (3 gm/m2) on days 1,3 and 5 Q12H] with a condensed dosing schedule, viz, the same drug at the same dose given on days 1, 2 and 3 Q12H and assess the merits and demerits in terms of time to hematologic recovery, toxicity, adverse effects and quantum of supportive care required during the hospital stay. Definition of the Problem: Acute myeloid leukaemia is a dreaded hematologic malignancy with a poor outcome. IHTM, being an apex centre for haematology in the state of West Bengal, registers numerous patients of AML every year. Definition of Population: Patients diagnosed as AML, and who have undergone successful induction chemotherapy in the institute will be recruited. Material and Methods:- Study Setting: Institute of Haematology and Transfusion Medicine, (IHTM), inpatient department (ward), Medical College and Hospital, Kolkata. Timeline: 1. Recruitment: May 2020 onwards 2. Study method: Each AML patient after successful completion of induction chemotherapy with documented morphological remission in bone marrow will be admitted to the IHTM ward. After taking informed consent and computer-based random number generation (randomization), the patient will be given chemotherapy from day 1 of admission as per either the condensed or the conventional schedule. Subsequently, the patients will receive Inj Filgrastim 5mcg/kg/day from day 4 in the condensed arm and day 6 in the conventional arm, till complete haematological recovery. 3. Study period: i. Initiation of study period: day 1 of chemotherapy. ii. Completion of study period: day of achieving complete haematological recovery (absolute neutrophil count > 1000/cumm; platelet count > 100,000/cumm; transfusion independence). Approximately one month per cycle for each patient. (Based on existing clinical practice) reference: Jaramillo S, Benner A, Krauter J, Martin H, Kindler T, Bentz M, Salih HR, Held G, Köhne CH, Götze K, Lübbert M, Kündgen A, Brossart P, Wattad M, Salwender H, Hertenstein B, Nachbaur D, Wulf G, Horst HA, Kirchen H, Fiedler W, Raghavachar A, Russ G, Kremers S, Koller E, Runde V, Heil G, Weber D, Göhring G, Döhner K, Ganser A, Döhner H, Schlenk RF. Condensed versus standard schedule of high-dose cytarabine consolidation therapy with pegfilgrastim growth factor support in acute myeloid leukemia. Blood Cancer J. 2017 May 26;7(5):e564. doi: 10.1038/bcj.2017.45. PubMed PMID: 28548643; PubMed Central PMCID: PMC5518888.
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