Only one patient was enrolled. Due to low accrual study was terminated

This study is a means of providing transplantation to those patients who would be a stem cell transplant candidate who do not have an appropriate donor.

The use of CD34 selected haploidentical donor with an umbilical cord unit may help provide earlier engraftment without the need for long term immunosuppression.

This study tests a new method of bone marrow transplantation called combined haploidentical-cord blood transplantation. In this procedure, some of the blood forming cells (the stem cells) from a partially human leukocyte antigen (HLA) matched (haploidentical) related donor are collected from the blood, as well as cells from an umbilical cord are transplanted into the patient (the recipient) after administration of a "conditioning regimen". A conditioning regimen consists of chemotherapy and sometimes radiation to the entire body (total body irradiation, or TBI), which is meant to destroy the cancer cells and suppress the recipient's immune system to allow the transplanted cells to take (grow).

This method of stem cell transplantation is designed to overcome some of the limitations of other alternative donor transplant options. Use of unrelated umbilical cord unit (UCB) donors appears to allow a greater degree of HLA mismatch with acceptable rates of GVHD. However, when UCB transplant was studied in the adult population, investigators discovered several limitations. One major limitation with UCB was delayed engraftment, resulting in higher risk of infection in the early post transplant period. The limitations to cord blood transplant involve delayed engraftment resulting in early complications such as infections. The main limitation associated with haploidentical donors is the significant immunosuppression required to prevent/treat aGVHD. Use of this combined modality of transplantation appears to allow for rapid neutrophil engraftment from the haploidentical donor and coupled with long term hematopoiesis from the UCB donor, thus requiring less long term immunosuppression.

This study tests a new method of bone marrow transplantation called combined haploidentical-cord blood transplantation. In this procedure, some of the blood forming cells (the stem cells) from a partially HLA matched (haploidentical) related donor are collected from the blood, as well as cells from an umbilical cord are transplanted into the patient (the recipient) after administration of a "conditioning regimen". A conditioning regimen consists of chemotherapy and sometimes radiation to the entire body (total body irradiation, or TBI),

One of two 'conditioning regimens' which will be determined by the physician.

1. FLUDARABINE, MELPHALAN, ATG

   Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1)

2. FLUDARABINE, BUSULFAN, 400 CGY TBI, ATG Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2) 400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1)

Day 0 -Haploidentical donor and one umbilical cord blood unit infusion

Filgrastim will be administered daily from day +1 until blood counts have completely recovered. Tacrolimus and another immunosuppressant, Cellcept, starting before transplant also to reduce the risks of graft versus host disease and to promote the growth of the graft. Tacrolimus will be given daily from two days before the transplant until at least three months after transplantation. Cellcept, will be tapered after the cells engraft.

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