Pilot Study of Unrelated Cord Blood Transplantation

DISEASE INCLUSION CRITERIA: In general this encompasses all haematological disorders where a volunteer unrelated donor transplant is clinically indicated. 1. Acute, chronic leukaemia or myelodysplastic syndrome for which allogeneic transplantation is considered as the best treatment option. 1. Acute myeloid leukaemia (AML) in first complete remission (CR1) with one of the following characteristics: * High risk cytogenetic or molecular alterations (e.g. t(9;22), deletion 7/7q-, monosomy 5 or del(5q), 3q26 alterations, complex karyotype \[3 or more anomalies\], p53 alterations, 11q23 especially t(6;11) abnormalities, FLT-3 ITD) * Leukocytes at diagnosis \> 50 x109/l (except in cases with good prognosis molecular rearrangements for which leukocytes should be \> 100 x 109/l) 2. Myelodysplastic syndromes * International Prognosis Index (IPSS) above 1 (intermediate group 2 or high risk) * IPSS 0 or 0.5 in the presence of cytopenias requiring treatment. 3. Therapy related AML or MDS in first CR 4. AML or MDS in second (CR2) or subsequent CR 5. Ph'-positive chronic myeloid leukaemia i. In first chronic phase if refractory and/or intolerance to tyrosine kinase inhibitors is clearly demonstrated ii. In second chronic phase 2. Acute lymphoblastic leukaemia (ALL) a. In CR1 with one of the following characteristics: i. Very high risk chromosome or molecular alterations (e.g. t(9;22), t(4;11), complex karyotype in adults, bcr/abl rearrangements, MLL rearrangements) ii. Slow response to induction treatment defined as the presence of \>10% blasts in bone marrow at day 14 of induction treatment iii. Adults aged \> 30 years iv. Adults with B ALL cell line with a number of leukocytes at diagnosis \>25 x 109/L or T ALL cell line with a number of leukocytes at diagnosis \>100X109/L b. In CR2 or subsequent CR 3. Non-Hodgkin's lymphoma 1. Follicular NHL: in second or subsequent complete or partial remission 2. Mantle cell NHL: in second or subsequent complete or partial remission 3. High grade NHL: in second complete or very good partial remission 4. Hodgkin's disease a. in second or subsequent complete or partial remission 5. Chronic lymphocytic leukaemia. 1. in second or subsequent remission 2. with adverse risk prognostic features in first remission 6. Acquired bone marrow failure syndromes 7. Other haematological malignancies for which UD bone marrow transplantation is indicated PATIENT SELECTION Inclusion criteria: myeloablative conditioning regimen 1. Aged under 35 years and greater than 18 years 2. Absence of HLA compatible related donor. 3. Need for an urgent transplantation or absence of HLA-compatible VUD after searching the international registries. 4. Patients with a HLA-compatible VUD but whose donor is considered by the transplantation centre as unsuitable will also be eligible. 5. Availability of suitable UD-UCB unit/s. 6. Informed consent. Exclusion criteria: myeloablative conditioning regimen 1. Patients with an available 5-6/6 HLA-A, -B, -DRB1 matched sibling donor or 10/10 unrelated bone marrow donor 2. ECOG performance status worse than 2 3. Cardiac insufficiency requiring treatment, symptomatic coronary artery disease or LVEF less than 40%. 4. Hepatic disease, with total bilirubin above 20umol/l or AST \> 3 times upper limit of normal. 5. Severe hypoxaemia, pO2 \< 70 mm Hg, with decreased DLCO \< 70% of predicted; or mild hypoxemia, pO2 \< 80 mm Hg with severely decreased DLCO \< 60% of predicted. 6. Impaired renal function (creatinine \> 2 times upper limit of normal or creatinine clearance \< 50% for age, gender, weight). 7. Patients who have received previous treatment with Thymoglobulin® 8. HIV or HTLV positive patients. 9. Female patients who are pregnant or breast feeding due to risks to foetus from conditioning regimen and potential risks to nursing infants. 10. Life expectancy severely limited by diseases other than the disease indication for transplant 11. Serious concurrent untreated infection e.g. active tuberculosis, mycoses or viral infection 12. Serious psychiatric/ psychological disorders 13. Absence of /inability to provide informed consent 14. Serious diseases that prevent treatments with chemotherapy 15. Myelofibrosis Inclusion criteria: reduced-intensity conditioning regimen (For both FluMel \& FluCyTBI regimens): 1. Age under 70 years and older than 18 years 2. Absence of HLA compatible related donor. 3. Need for an urgent transplantation or absence of HLA-compatible VUD after searching the international registries. 4. Patients with a HLA-compatible VUD but whose donor is considered by the transplantation centre as unsuitable will also be eligible. 5. Availability of suitable UD-UCB unit/s. 6. Informed consent. Exclusion Criteria: reduced-intensity conditioning regimen (For both FluMel \& FluCyTBI regimens): 1. Patients with an available 5-6/6 HLA-A, -B, -DRB1 matched sibling donor or 10/10 unrelated bone marrow donor 2. ECOG performance status worse than 2 3. Cardiac insufficiency requiring treatment, symptomatic coronary artery disease or LVEF less than 35%. 4. Hepatic disease, with total bilirubin greater than 2 times upper limit of normal or AST \> 5 times upper limit of normal. 5. Severe hypoxaemia, pO2 \< 70 mm Hg, with decreased DLCO \< 50% of predicted; or mild hypoxemia, pO2 \< 80 mm Hg with severely decreased DLCO \< 50% of predicted. 6. Impaired renal function (creatinine \> 2 times upper limit of normal or creatinine clearance \< 50% for age, gender, weight). 7. Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI). 8. Patients who have received previous treatment with Thymoglobulin® 9. HIV or HTLV positive patients. 10. Female patients who are pregnant or breast feeding due to risks to foetus from conditioning regimen and potential risks to nursing infants. 11. Life expectancy severely limited by diseases other than the disease indication for transplant 12. Serious concurrent uncontrolled infection e.g. active tuberculosis, mycoses or viral infection 13. Serious psychiatric/ psychological disorders 14. Absence of /inability to provide informed consent 15. Within 6 months of prior myeloablative transplant. 16. Patients with acute leukaemia in morphological relapse/ persistent/ progressive disease 17. Intermediate or high grade NHL, mantle cell NHL and Hodgkin's disease that is refractory or progressive on salvage therapy. 18. Myelofibrosis