This trial investigates stem cell transplants from partially mismatched donors in patients with blood and bone marrow cancers. The trial will test two kinds of transplants - a full intensity transplant using a high dose of radiotherapy and chemotherapy, and a reduced intensity transplant with lower doses of chemotherapy and radiotherapy. Patients will be entered for the treatment pathway that is most appropriate for their level of health and fitness

Patient Inclusion Criteria

1. Eligible for an allogeneic transplant in line with the current BSBMT indications for transplant criteria (http://bsbmt.org/indications-table/) accepted by Commissioners

2. Age 16-70

3. Adequate physical function

   • Cardiac: LVEF at rest ≥45%, or shortening fraction ≥25%
   • Hepatic: Bilirubin ≤35mmol/l; AST/ALT and alkaline phosphatase <5 x ULN
   • Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, creatinine clearance or GFR >40ml/min/1.73m2
   • Pulmonary: FEV1, FVC, DLCO (diffusion capacity) >50% predicted (corrected for haemoglobin); if clinically unable to perform pulmonary function tests then O2 saturation >92% on room air
   • Performance status: Karnofsky score ≥60%

4. Donor available aged ≥16 years

5. Needs an urgent transplant where a 10/10 HLA matched sibling or unrelated donor is unavailable in a timely manner. An unrelated donor search is not required for a patient to be eligible if the clinical situation dictates an urgent transplant. Clinical urgency is defined as 6-8 weeks from referral to transplant centre or low likelihood of finding a matched unrelated donor

6. HLA typing will be performed at high resolution (allelic) for the HLA-A, HLA-B, HLA-Cw, HLA-DRB1 and HLA-DQB1 loci. A minimum match of 5/10 is required

7. The donor and recipient must be identical as determined by high resolution typing at at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1 and HLA-DQB1. Fulfilment of this criterion is sufficient evidence that the donor and recipient share one HLA haplotype and typing of additional family members is not required.

8. Patient must have received cytotoxic chemotherapy within 3 months of the consent date (measured from the start date of the most recent cycle of chemotherapy) except patients with aplastic anaemia, unless otherwise agreed by the TMG (see section 5.3.4). The use of monoclonal antibody therapy may be considered cytotoxic chemotherapy, but must be agreed by the TMG

9. Written informed consent

Donor Inclusion Criteria

1. Donor must be an HLA-haploidentical first degree relative of the patient. Eligible donors include biological parents, siblings, children or half-siblings
2. Age ≥16 years
3. Donors must meet the collection centre's usual selection criteria for related allogeneic HPC donors

Patient Exclusion Criteria

1. HLA matched, related donor able to donate
2. Autologous haematopoietic stem cell transplant <3 months prior to enrolment
3. Pregnancy or breastfeeding
4. Uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiological findings), the inclusion of patients with an uncontrolled viral or fungal infection can be agreed by the TMG
5. Serious psychiatric or psychological disorders
6. Absence or inability to provide informed consent
7. Severe comorbidity (HCT-CI comorbidity score of 3 or more) or disease that prevents treatment with chemotherapy, unless otherwise agreed by the TMG
8. Positive anti-donor HLA antibody
9. Unable to receive 2Gy TBI (RIC pathway) or 12Gy TBI (MAC pathway)
10. Patients with graft rejection following a previous allograft from either adult or cord blood donors

Donor Exclusion Criteria

1. Positive anti-donor HLA antibody in the recipient
2. Pregnancy or recent birth (within 6 months prior to donating cells)