Hematopoietic Stem Cell Transplantation (HSCT) Using CD34 Selected Mismatched Related Donor and One Umbilical Cord Unit (Haplo/Cord)

Inclusion Criteria:

• Patients between 18 and 65 years old
• Patient has a related family member(haploidentical) or unrelated which is 5 of 10 HLA identical match.

Standard Risk

• Acute myelogenous leukemia: CR1 with high risk cytogenetics or molecular abnormalities such as FLT-3 ITD, or CR2 with a first remission that must have lasted > 1 year.
• Acute Lymphocytic Leukemia: CR1, in order to be standard risk must NOT have Philadelphia Chromosome.
• Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): Must be refractory to fludarabine or fail to have a complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. 2-CDA, pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog).
• Chronic myelogenous leukemia: resistant to or intolerant of TKI, in CP1 or CP2, or with a mutation that suggests resistance to TKI.
• Myelodysplastic Syndrome: RA, RARS, must be IPSS ≥ INT-2, Blasts <5%.

High Risk Patients:

• Acute myelogenous leukemia: Patients with CR2 are considered high risk if they have high risk cytogenetics, or molecular abnormalities or CR1 lasted for less than 1 year. Any evidence of active disease or no blasts in an acellular marrow.
• Acute Lymphocytic Leukemia: CR1- with Ph+ disease, CR2/+ with any cytogenetics. Any evidence of active disease.
• Chronic myelogenous leukemia- CP2/+, AP1/+, resistant or intolerant to TKI.
• Hodgkin's or Non Hodgkin's lymphoma- Disease recurrence following an autologous transplant, or high risk disease not thought to benefit from autologous transplant.
• Chronic lymphocytic leukemia- that is resistant to fludarabine, and never has been in remission or with stable disease/progressive disease
• Multiple myeloma: Must have had prior treatment. Patients in CR2 or greater can be considered, must have already failed autologous transplant Previous autologous transplant,must have been greater than 6 months prior to undergoing this transplant.
• Myelodysplastic syndrome: RAEB
• Other Myeloproliferative disorders including myelofibrosis, spent phase p Vera,Essential thrombocytosis,CMML.

Exclusion Criteria:

• Patients <18 years old Disease related criteria
• APML, presence of t(15,17) in first CR
• Patients with good risk AML, for example t(8;21), or inv 16, or normal cytogenetics with FLT-3-ITD negative, NPM-1 positive disease in 1st CR
• MDS IPSS < INT-2 Miscellaneous Criteria
• Recipients who have a matched related sibling or unrelated donor
• If recipient has evidence of anti-HLA antibodies directed against cord or haplo-donor as determined byflowPRA.

Underlying health criteria:

• Zubrod performance status > 2 (see Appendix E)
• Life expectancy is limited to less than 8 weeks by concomitant illness
• Patients with severely decreased LVEF (EF < 40%)
• Impaired pulmonary function tests (PFT's) (FVC, FEV1, DLCO < 45% predicted)
• Estimated Creatinine Clearance <50 ml/min
• Serum bilirubin> 2.0 mg/dl or SGPT >3 x upper limit of normal
• Evidence of chronic active hepatitis or cirrhosis
• HIV-positive
• Patient is pregnant
• Patient or guardian not able to provide informed consent