INDICATIONS Cyclophosphamide/Rabbit Anti-Thymocyte Globulin for Allograft Aplastic Anaemia (patients under 40 years) PRE-ASSESSMENT Ensure pre-transplant work-up form is complete Ensure patient has triple lumen line inserted and working Ensure results of pre-transplant investigations are checked and recorded in patient record Complete BMT front sheet and file in patient record Prescribe chemotherapy and supportive treatment 10 days prior to admission Send NBS request form 2J to NHSBS for processing of bone marrow/pbsc and ensure a copy is placed in the medical notes Ensure that patient receives irradiated blood products from the start of conditioning and indefinitely thereafter Ensure that patient receives CMV negative blood product, if patient is CMV seronegative, from the start of conditioning and indefinitely thereafter Ensure pregnancy test is carried out on all women of child-bearing potential on day -7 SUMMARY Day DRUG -6-5 -4-3 -2-1 0 +1 +3 +6 +11 Admission * Heparin * * * * * * * cont Cyclophosphamide * * * * Mesna * **** **** **** *** Rabbit ATG (rbatg) test dose * Methylprednisolone * * * rbatg * * * Pentamidine * Bone marrow infusion * Ciclosporin ** ** cont Guide to first-line antiemetics: M M M M M M M= Metoclopramide Methotrexate Days +1,+3,+6, (+11) * * * (*) Version 6 Page 1 of 8 Cy/ATG for Allo
CHEMOTHERAPY AND FLUIDS Encourage 3L oral fluids daily, give iv if oral intake insufficient. Day 5 14.00 15.00 Note ATG Test dose 2.5mg/one time only/iv in 100ml sodium chloride 0.9% over 1 hour through a 0.22 micron filter. Flush with sodium chloride 0.9% Test dose must be supervised by a doctor with adrenaline, chlorphenamine, hydrocortisone drawn up beforehand. Each ATG dose must be completed within 18 hours of being made up. Platelet count must be maintained > 30 but platelet transfusion should not be given concurrently with ATG because of it s anti-platelet activity. If possible avoid giving more than 1 unit of red cells each day of ATG to help avoid the risk of fluid overload. 22.00 500ml glucose 5% over 2hrs 23.30 Furosemide 20mg iv, then prn to maintain urine output of >100ml/hr 24.00 (T=0) Cyclophosphamide 50mg/kg iv od in 250ml sodium chloride 0.9% over 1 hour 24.00 (T=0) Mesna 24mg/kg iv Day 4 T=3,6 &9 hours Mesna 24mg/kg iv 01.00 1000ml sodium chloride 0.9% over 8hrs 09.00 1000ml glucose 5% over 8hrs 11.00 Chlorphenamine 10mg iv bolus 1 hour pre ATG 11.30 Methylprednisolone 2mg/kg iv infusion in 100mls sodium chloride 0.9% over 30 minutes. To be commenced 30 minutes before ATG Version 6 Page 2 of 8 Cy/ATG for Allo
Note Each dry powder vial contains 25mg rbatg Dose required is 1.5 vials / 10 kg body weight which is equivalent to 3.75mg/kg. Serum sickness: Reactions such as fever, rash, arthralgia, and/or myalgia may occur 5 14 days after starting ATG therapy. Symptoms are usually self- limited or resolve rapidly to corticosteroids. 12.00 ATG 3.75mg/kg iv od in 500-1000ml sodium chloride 0.9% over 12hrs through a 0.22 micron filter 17.00 1000ml sodium chloride 0.9% over 7hrs 22.00 500ml glucose 5% over 2hrs 23.30 Furosemide 20mg iv, then prn to maintain urine output of >100ml/hr 24.00 (T=0) Cyclophosphamide 50mg/kg iv od in 250ml sodium chloride 0.9% over 1 hour 24.00 (T=0) Mesna 24mg/kg iv Day 3 T=3,6 &9 hours Mesna 24mg/kg iv 01.00 1000ml sodium chloride 0.9% over 8hrs 09.00 1000ml glucose 5% over 8hrs 11.00 Chlorphenamine 10mg iv bolus 1 hour pre ATG 11.30 Methylprednisolone 2mg/kg iv infusion in 100mls sodium chloride 0.9% over 30 minutes. To be commenced 30 minutes before ATG 12.00 ATG 3.75mg/kg iv od in 500-1000ml sodium chloride 0.9% over 12hrs through a 0.22 micron filter 17.00 1000ml sodium chloride 0.9% over 7hrs Version 6 Page 3 of 8 Cy/ATG for Allo
22.00 500ml glucose 5% over 2hrs 23.30 Furosemide 20mg iv, then prn to maintain urine output of >100ml/hr 24.00 (T=0) Cyclophosphamide 50mg/kg iv od in 250ml sodium chloride 0.9% over 1 hour 24.00 (T=0) Mesna 24mg/kg iv Day 2 T=3,6 &9 hours Mesna 24mg/kg iv 01.00 1000ml sodium chloride 0.9% over 8hrs 09.00 1000ml glucose 5% over 8hrs 11.00 Chlorphenamine 10mg iv bolus 1 hour pre ATG 11.30 Methylprednisolone 2mg/kg iv infusion in 100mls sodium chloride 0.9% over 30 minutes. To be commenced 30 minutes before ATG 12.00 ATG 3.75mg/kg iv od in 500-1000ml sodium chloride 0.9% over 12hrs through a 0.22 micron filter 17.00 1000ml sodium chloride 0.9% over 7hrs 22.00 500ml glucose 5% over 2hrs 23.30 Furosemide 20mg iv, then prn to maintain urine output of >100ml/hr 24.00 (T=0) Cyclophosphamide 50mg/kg iv od in 250ml sodium chloride 0.9% over 1 hour 24.00 (T=0) Mesna 24mg/kg iv Version 6 Page 4 of 8 Cy/ATG for Allo
Day 1 T=3,6 &9 hours Mesna 24mg/kg iv 01.00 1000ml sodium chloride 0.9% over 8hrs 09.00 1000ml glucose 5% over 8hrs Day 0 06.00 12.00 Marrow/PBSC infusion (minimum 36 hrs post cyclo) 1000ml sodium chloride 0.9% +20mmol potassium chloride over 6 hours Give hydrocortisone 100mg iv, chlorphenamine 10mg iv 30 minutes before cell infusion. Day +1 Pentamidine 4mg/kg/day/iv (max 300mg) in 100ml sodium chloride 0.9% over 1 hour Day +1 Methotrexate 15mg/m2 iv bolus (min. 24hr post cell infusion) Day +3, +6, (+11) At the same time as Day 1 Methotrexate 10mg/m2 iv bolus (Day 11, check with consultant). ADMINISTRATION OF CHEMOTHERAPY; Refer to nursing care plan N.9 ADMINISTRATION OF ATG: Refer to nursing care plan N.6 BONE MARROW INFUSION: Refer to nursing care plan N.51 or N.18 DOSE MODIFICATION Consider dose reduction in renal impairment, discuss with consultant. ANTI-EMETICS Day -5 to 0 Metoclopramide 20mg iv/po qds Version 6 Page 5 of 8 Cy/ATG for Allo
CONCURRENT MEDICATION Norethisterone 5-10mg po TDS from day 0 until platelets >50x10 9 /l (menstruating women only) Fluconazole 50mg OD po from day 0 until neutrophils >1.0x10 9 /l (or longer if on steroids) Pentamidine 4mg/kg/day iv on day +1 and day +30 (unless started on to co-trimoxazole). Aciclovir For CMV Prophylaxis If either donor or recipient or both are CMV + then: 500mg /m 2 TDS iv or 800mg po QDS day -7 to day +30 then 800mg po QDS for 3 months, then 200mg TDS for further 3 months if VZV positive If both donor and recipient are CMV negative then consider HSV/VZV Prophylaxis Aciclovir dose is 250mg iv TDS or 200mg po TDS Duration of treatment depends on HSV and VZV status of recipient: HSV neg and VZV neg no aciclovir needed HSV pos and VZV neg treat for 3 months HSV pos and VZV pos treat for 6 months HSV neg and VZV pos treat for 6 months Ciclosporin (Neoral) Heparin 1.5mg/kg iv BD - total dose 3mg/kg/day (adjust for renal toxicity) in 20-100ml sodium chloride 0.9% over 2-4hrs from day 1. See protocol. Change to po prior to discharge. See Medication on Discharge 200iu/kg/48hr infusion in 48ml sodium chloride 0.9% infused at 1ml/hr from admission to day +30 or discharge Omeprazole 20mg OD from start of conditioning until platelet count >50x10 9 /l INVESTIGATIONS Daily FBC, creatinine, urea & electrolytes, weight, urinalysis Alternate days Liver function tests Mon/Thurs Group and save, clotting, calcium, magnesium, phosphate Weekly Zinc, urate Monday Ciclosporin levels - trough level. See protocol. CMV PCR from Day+14 if either patient or donor is CMV positive Other specimens for virology as clinically indicated. Version 6 Page 6 of 8 Cy/ATG for Allo
MEDICATION ON DISCHARGE (TTOs) Norethisterone Fluconazole Co-trimoxazole Aciclovir Ciclosporin (Neoral) Omeprazole Penicillin V Stop when platelets >50 x 10 9 /l (menstruating women only) Stop when neutrophils > 1x 10 9 /l (longer if patient on steroids) 960mg OD Mon, Wed, Fri until day +120, start when neutrophils >1x10 9 /l and continue until one month after immunosuppressive therapy stopped Consider prophylaxis with Pentamidine 4mg/kg iv monthly, if patient allergic to co-trimoxazole Depends on CMV/ HSV/ VZV status, refer to page 6 of this protocol On discharge the patient should be prescribed an oral dose of twice the last intravenous dose. See protocol. Check with registrar or consultant. In patients with aplastic anaemia ciclosporin should be continued for 9 months and then tailed over 3 months in the absence of GVHD. Stop unless clinically indicated 250mg BD continuously, to start when co-trimoxazole is stopped REFERENCES MarshJCW, Ball SE, Cavenagh J et al. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol. 2009; 147 ; 43-70 Thymoglobuline 25mg powder for solution for infusion - Summary of Product Characteristics www.medicines.org.uk/emc/medicine/20799/spc/thymoglobuline+25mg+p Storb R et al. Cyclophosphamide and antithymocyte globulin to condition patients with aplastic anaemia for allogeneic marrow transplantations: the experience in four centres. Biol Blood Marrow Transplant. 2001; 7(1): 39-44. Storb R et al Cyclophosphamide combined with anti-thymocyte globulin in preparation for allogeneic marrow transplants in patients with aplastic anaemia Blood 1994; 84(3): 941-49 Author Tim Littlewood, BMT Programme Director 2006 Version 6 Page 7 of 8 Cy/ATG for Allo
Review Name Revision Date Version Review date Denise Wareham, BMT Coordinator Equine ALG to Rabbit ATG Addition of Methylprednisolone Jan 2011 V.6.0 Jan 2012 Circulation BMT Protocol file Haem Ward, DTU Pharmacy TSSG website Version 6 Page 8 of 8 Cy/ATG for Allo