GUIDELINES FOR THE MANAGEMENT OF ADULT ACUTE LEUKAEMIA INITIAL MANAGEMENT CONSIDERATIONS N.B.: If AML is suspected definitively diagnosed, please ensure that the patient is transferred immediately f treatment to a Level 2+ Haematology unit. This can be discussed with the AML lead MDT lead in your Haematology MDT if needed. Please ensure transfer is undertaken as soon as AML is suspected such that the patient can have appropriate level 2 nursing and supptive care, and that appropriate clinical trials are considered and enrolment/treatment can occur in a timely fashion. Ideally, a bone marrow should be undertaken at the Leukaemia unit after transfer if clinically appropriate. A. Supptive Care Patients should be nursed in isolation rooms with reverse barrier nursing to prevent infections. Clean, neutropenic diets should be instituted and appropriate infection control measures should be undertaken. Prophylaxis and treatment of infection from presentation should be instituted based on local protocols with antibiotic choice largely dependent on local microbiological fla. F patients who will undergo intensive treatment schedules, a Hickman Line should be inserted as soon as is safely possible. B. Hyperleukocytosis Syndrome Definition Hyperviscosity due to an elevated leukaemic blast cell number in the peripheral blood circulation, the increased viscosity causes leukostasis within vulnerable capillary regions and ischaemia of tissues with occasional infiltration of leukaemic cells into the tissues themselves causing gan compromise. Symptoms of leukostasis occur at different blast cell count thresholds, depending on the leukaemic subtype. Patients with acute myeloid leukaemia are at highest risk and may experience symptoms with blast counts as low as 25 x 10 9 /L (especially in the monoblastic subtype), but typically the blast count is greater than 50 x 10 9 /L when symptoms occur. Leukapheresis The need f leukapheresis is determined by symptoms and risk stratification - a high leukocyte count is not in itself an indication f urgent leukapheresis. Patients with features (even very early) of leukostasis (e.g. pulmonary infiltrates, hypoxia, CNS changes, renal failure, cardiac ischaemia, priapism, severe retinopathy) should undergo leukapheresis as an emergency. C. Initial cyteduction with hydroxycarbamide F patients with high white cells counts, with symptoms ( at risk) of leukostasis, treatment with hydroxycarbamide should be started as a matter of urgency until definitive cyteductive can be administered. Treatment may be commenced with 2 Acute Leukemias Intro 2 8.docAcute_Leukaemias_Intro_2.8_Feb12.doc Page 1 of 6
grams every 6-8 hours daily to aim f rapid reduction of leukocyte counts together with rasburicase 0.20 mg/kg/day administered as a once daily 30 minute intravenous infusion in 50 ml of a sodium chlide 0.9% solution ( allopurinol 300mg/day ally if rasburicase contraindicated, e.g. G6PD deficiency), and adequate hydration. Saline hydration with additional bicarbonate to alkalinise urine may be instituted, with fced diuresis if necessary, to reduce the symptoms of leukostasis and to reduce the adverse effects of tumour lysis. Aggressive supptive measures (as indicated by the patient s perfmance status pri to the diagnosis of leukaemia) are advised. This may include ventilaty, and dialysis suppt until definitive cyteduction can be accomplished and thereafter as deemed appropriate. D. Blood transfusion Administer CMV negative blood products until the patient s CMV status is known. Red cell transfusions should be avoided if there is any risk of leukostasis. All platelet products should be single don collections in der to limit the risk of allo-sensitization. HLA-typing should be done pri to starting treatment in der to address don status if transplantation is appropriate f the patient and in case HLA-matched platelets become necessary during treatment (as often occurs in women who have had children especially). Irradiated blood products should be requested f patients on protocols containing Fludarabine, Cladrabine and Clofarabine E. Preservation of fertility Semen cryopreservation should be considered f all men below the age of 50. The possible need f embryo cryopreservation should be considered f women, although urgency of treatment does not usually allow f this. Contact the Andrology Department at the Hammersmith Hospital: 020 3313 4680 to arrange details of collection. Acute Leukemias Intro 2 8.docAcute_Leukaemias_Intro_2.8_Feb12.doc Page 2 of 6
1. ACUTE MYELOID LEUKAEMIA (AML) Treatment Algithm Consider all patients f entry into clinical trials Not eligible f trials Not APML (not AML M3) APML (AML M3) see page2 Start supptive treatment, consider emergency cyteduction with and sperm cryopreservation Patient fit f aggressive Patient not fit f aggressive Induction DA, ADE FLAG +/- Ida 20-30% blasts >30% blasts Risk of relapse assessment Refracty Fit f reinduction? Supptive care + Low intensity treatment e.g. azacitidine (NICE), s.c. ara- C, ACE, EZ hydroxyurea Supptive care +/- cyteductive : hydroxycarbamide (hydroxyurea), etoposide, mitoxantrone low dose cytarabine Low Standard High Yes No ACE 2 nd induction followed by one two consolidation courses (MACE, MiDAC, Mylotarg x1 HDAC) Consider Consider allograft after 2 nd induction 1 st consolidation HLA type siblings and discuss with transplant centre Reinduction (FLAG+/-Ida, HDAC, CIA, D-Clo, CLAG) Refracty Acute Leukemias Intro 2 8.docAcute_Leukaemias_Intro_2.8_Feb12.doc Page 3 of 6 EZ
APML Treatment Algithm AMPL (AML M3) ATRA should be started as soon as APML is suspected. Start supptive treatment (crect coagulation, keep platelet count > 50 x10^9/l), leucopheresis is contraindicated Patient fit f Patient not fit f AIDA risk adapted PETHEMA LPA 2005 ATRA +/- low dose Arsenic +/- ATRA Acute Leukemias Intro 2 8.docAcute_Leukaemias_Intro_2.8_Feb12.doc Page 4 of 6
2. ACUTE LYMPHOBLASTIC LEUKAEMIA (ALL) ALL Treatment Algithm (excluding Burkitts Lymphoma (ALL FAB L3)) Consider all patients f entry into clinical trials Not eligible f trials Start supptive treatment, consider emergency cyteduction with and sperm cryopreservation Patient fit f aggressive Patient not fit f aggressive Induction (UK ALL 12, 14 UK 2003 protocols), use tyrosine kinase inhibit as per protocol if Ph+; Tissue type siblings Ph positive Ph negative Refracty Supptive care +/- Tyrosine kinase inhibit Supptive care +/- cticosteroids Continue on the protocol and consider stem cell transplantation Fit f salvage Yes No cyteductive (vincristine, hydroxycarbamide, etoposide, clofarabine) Reinduction (FLAG+/-Ida, Hyper-CVAD, CLAG+/-Ida, Clofarabine, CIA,) Refracty Acute Leukemias Intro 2 8.docAcute_Leukaemias_Intro_2.8_Feb12.doc Page 5 of 6
Written by: Dr N Panoskaltsis and Pauline McCalla Authised by: NWLCN Haematology TWG February 2012 Date f review by Haematology TWG: February 2014 Acute Leukemias Intro 2 8.docAcute_Leukaemias_Intro_2.8_Feb12.doc Page 6 of 6