A Phase II Study of Parathyroid Hormone Following Myeloablative Sequential Unrelated Cord Blood Transplantation

Inclusion Criteria - myeloablative arm:

1. Disease criteria:

   1. CML accelerated phase or second stable phase. Patients in first chronic phase are eligible if they have resistance to imatinib.
   2. Myelodysplasia.
   3. Aplastic Anemia, not responding to immunosuppressive therapy.
   4. Myelofibrosis, either primary or secondary to polycythemia vera.
   5. Relapsed lymphoma or Hodgkin's disease.
   6. Stage III/IV CLL, relapsed after or refractory to at least one fludarabine containing regimen.
   7. AML or ALL in CR 2 or greater or CR 1 with high risk features. Complete remission or CRp as defined by WHO criteria are acceptable.50
2. Age 18-50 years.
3. No prior autologous stem cell transplant.
4. ECOG Performance status of <2.
5. The patient and the cord blood units must be a 4/6 allele level HLA A, B, DRB1 match or greater with each other and the patient.
6. Total combined nucleated cell dose from the 2 cord blood units > 3.7 x 107NC/kg (pre-freeze dose). Each single cord blood unit cell dose must be > 1.5 x 107NC/kg.
7. Lack of 6/6 or 5/6 matched related donor or lack of 10/10 matched unrelated donor, or a donor is not available in time frame to perform a potentially curative stem cell transplant.
8. DLCO >50% predicted (corrected for hemoglobin).
9. LVEF > 50%
10. Calcium <10.5 mg/dl, phosphate > 1.6 mg/dl.
11. Non-pregnant and non-nursing.

Inclusion criteria - reduced intensity arm

1. Disease-specific criteria

   1. Non-Hodgkin's lymphoma, or Hodgkin's lymphoma: in Complete Remission >2 (second complete remission, third complete remission, etc) or in partial remission.
   2. Multiple myeloma: relapsed.
   3. Chronic lymphocytic leukemia, Rai stage III or IV, or lymphocyte doubling time of 6 months, or stage I-II, having progressed after > 2 chemotherapy regimens, in partial remission.
   4. Acute myelogenous or lymphoblastic leukemia in second or subsequent remission or in first remission with adverse cytogenetics or antecedent hematologic disorder. Complete remission or CRp as defined by WHO criteria are acceptable.
   5. Chronic myelogenous leukemia in accelerated or second stable phase, or imatinib resistant and not eligible for an ablative transplant.
   6. Myelodysplasia, previously treated or not eligible for ablative Version 9/27/2007 Page 12 of 44 transplant.
2. Age 18-65 years.
3. ECOG performance status of 0, 1, or 2.
4. The patient and the cord blood units must be a 4/6 allele level HLA A, B, DRB1 match or greater with each other and the patient.
5. Total combined nucleated cell dose from the 2 cord blood units > 3.7 x 107NC/kg (pre-freeze dose). Each single cord blood unit cell dose must be > 1.5 x 107NC/kg.
6. Lack of 6/6 or 5/6 HLA-matched related, 10/10 matched unrelated donor, or unrelated donor not available within the time frame necessary to perform a potentially curative stem cell transplant.
7. DLCO >50% predicted corrected for hemoglobin.
8. LVEF > 45%.
9. Calcium <10.5 mg/dl, phosphate > 1.6 mg/dl.
10. Not pregnant or nursing

Exclusion Criteria:

Exclusion criteria for eligibility for both regimens include:

1. Cardiac disease: symptomatic congestive heart failure, active angina pectoris, or uncontrolled hypertension.
2. Pulmonary disease: severe chronic obstructive lung disease, or symptomatic restrictive lung disease, or corrected DLCO of < 50% predicted.
3. Renal disease: serum creatinine > 2.0 mg/dl.
4. Hepatic disease: serum bilirubin > 2.0 mg/dl (except in the case of Gilbert's syndrome or hemolytic anemia in which the bilirubin can be elevated greater than 2.0mg/dl), SGOT or SGPT > 3 x upper limit normal.
5. Neurologic disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation (previous CNS malignancy, presently in CR is not exclusion).
6. HIV seropositive.
7. Uncontrolled infection.