Clinical guidelines for the management of Acute Myeloid Leukaemia (AML)

Transcription

1 Clinical guidelines for the management of Acute Myeloid Leukaemia (AML) Prepared by: Dr Salaheddin Tueger. Countess of Chester Hospital Consultant Haematologist On behalf of the Haematology CNG Revised by: Prof Richard Clark Consultant Haematologist Written: February 2010 Reviewed: May 2016 Review: No later than March 2017 Agreed: Haematology Clinical Network Group: May 2015 The patient should be considered for available NN/MRC trials at diagnosis and relapse. All clinical teams are encouraged to enter patients into trials. Notes: 1. Gemtuzumab Ozogamicin (Mylotarg) currently does not have a FDA licence and is therefore only available to patients within the AML 18 and 19 trials. 2. SOPRA (Selinexor in Older Patients with Relapsed AML) has been open at RLUH for newly diagnosed or relapsed / refractory AML who are unfit for intensive chemotherapy and/or Transplantation. 3. CAMELLIA A Phase I dose escalation trial of the Humanized Anti-CD47 Monoclonal Antibody Hu5F9-G4 in relapsed/refractory AML. Page 1 of 6

2 Management of non APML patients <60 (or fit >60) years, fit for intensive chemotherapy and not entered into a clinical trial DA /- Gemtuzumab ozogamicin (Mylotarg) (PCT funding may need to be sought) or PR (5-15% blasts) Refractory disease (>15%blasts) DA 3+8 x2 Not Good risk Inv 16, t (8;21) Poor risk cytogenetics -5, -7, del (5q), complex, abn 3q normal risk with FLT3ITD positive, NPM1 negative Standard risk; discuss with centre Donor sibling or unrelated ; discuss with centre (FLAG-Ida) x2 No Donor or unfit for No MACE or high dose ara-c Prepared by: Dr Tueger, negative, Countess of Chester Hospital Revised by Prof Richard NPM1 Clark positive Page 2 of 6 MidAC No sibling donor or unfit for allogeneic or FLT3ITD Sibling Donor and <55 (or <65 for RIC allo) allogeneic allogeneic Full/RIC/Sib /VUD further consolidation chemotherapy or experimental therapy

3 Management of Non APML patients >60 years Not fit for intensive treatment Fit for intensive treatment not entered into a clinical trial. DA /- Gemtuzumab Ozogamicin (Mylotarg) or PR (5-15% blasts) Resistant disease blasts >15% DA 3+8 No DA 2+5 RIC allo if patient fit Best supportive care Palliative treatment experimental therapy Not fit for intensive treatment and with poor cytogenetics such as monosomal karyotype (i.e. a monosomy plus complex abnormalities, or 2 or more monosomies, if eligible enter into the AML LI-1. If not eligible then Azacytidine (only for those with blast count of <30%, low dose cytosine or hydroxycarbamide and best supportive care should be offered. For relapsed disease patients if eligible should be entered into clinical trial open at RLUH, if NOT then palliative care with low dose cytosine or hydroxycarbamide. If a prolonged 1 st remission was achieved and the patient is fit, re-induction with DA followed by a RIC allo MCCN could AML be considered Guidelines OR Gemtuzumab Ozogamicin (Mylotarg) (Funding may need to be Prepared sought) by: Dr Tueger, Countess of Chester Hospital Page 3 of 6

4 Management of Non APML patients <60 (of fit>60) years With relapsed disease If patients are eligible should be offered to enter into clinical trial open at RLUH Relapsed disease 1 <12 months 1 >12 months High dose cytosine containing regimen High dose cytosine containing regimen or repeat first remission inducing treatment 2 No 2 Donor available (sib or unrelated) and fit for allo No donor or unfit for allo Best supportive care Palliative treatment experimental therapy Allo Sib/VUD/full/RIC autograft if cells stored from first or further consolidation chemotherapy/ experimental therapy haploidentical SCT in patients <30 Page 4 of 6

5 Management of APML patients <60 years (or fit >60) Not entered into a clinical trial APML suspected treat as below. If t (15; 17) not confirmed stop ATRA and treat as per non APML protocol Correct coagulopathy Hydration Avoid leukapheresis for high white counts Samples to be sent for MRD P monitoring AIDA protocol (see section 19 of AML17 protocol) Or ATO+ ATRA If no by Day 60 proceeds to high risk protocol see below) Management of APML for patients >60 years not fit for Intensive MRC type chemotherapy There is little evidence to guide management of these patients however various therapeutic options include the elderly variation of Spanish type therapy which may be less intensive than AIDA based regimens Or Arsenic + ATRA as first line treatment Or Mylotarg has some activity as a sole agent in APML but remissions are usually short lived Page 5 of 6

6 Management of patients with relapsed/refractory APML Confirm presence of PML/RARA translocation + send samples for MRD monitoring (BM+PB) Arsenic trioxide therapy 0.30mg/kg for 5 days followed by 0.25mg/kg twice weekly for up to 7 weeks Assess MRD at 28 days MRD negative MRD positive or no haematological Further 4 weeks of arsenic therapy then Autologous stem cell from MRD negative cells if harvested in first or following arsenic re-induction If not fit for autologous consider further consolidation therapy with arsenic trioxide (up to 4 courses in total) or maintenance therapy with MTX/6-MP and ATRA or experimental therapy If not fit for consider maintenance therapy with MTX/6- MP and ATRA Page 6 of 6 Continue arsenic +Idarubicin 10mg/m 2 on 2 consecutive days reassess MRD after further 2/52 MRD negative Haematological allogeneic stem cell MRD positive No haematological Mylotarg therapy If not fit for Mylotarg or no response, ATRA alone, best supportive treatment or experimental therapy