RATIONALE: Umbilical cord blood transplantation may be able to replace cells destroyed by chemotherapy or radiation therapy.

PURPOSE: Phase II trial to study the effectiveness of umbilical cord blood transplantation in treating patients who have hematologic cancer or other hematologic or metabolic diseases.

Condition	Treatment or Intervention	Phase
Graft Versus Host Disease Refractory Anemia Previously Treated Myelodysplastic Syndrome secondary myelodysplastic syndrome refractory anemia with ringed sideroblasts de novo myelodysplastic syndrome noninvasive malignant thymoma recurrent malignant thymoma	Drug: anti-thymocyte globulin  Drug: busulfan  Drug: cyclophosphamide  Drug: cyclosporine  Drug: melphalan  Drug: methylprednisolone	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the rates of durable engraftment in patients with severe aplastic anemia, myelodysplastic syndrome, inborn errors of metabolism, or inherited hematopoietic disorders refractory to medical management, who are undergoing high dose chemoradiotherapy followed by unrelated cord blood (UCB) transplantation.

II. Determine the incidence and severity of acute and chronic graft-versus-host disease in these patients.

III. Monitor overall and event-free survival of these patients.

IV. Evaluate rate and quality of immunologic reconstitution of these patients.

V. Determine whether nucleated cell or progenitor cell content of the graft is predictive of engraftment.

PROTOCOL OUTLINE: This is a multicenter study. Patients are stratified according to low vs high weight.

Patients with severe aplastic anemia, myelodysplastic syndrome, or bone marrow failure receive cyclophosphamide IV over 1 hour on days -6 to -3 or melphalan IV over 20 minutes on days -4 to -2, antithymocyte globulin (ATG) IV over 4 hours or methylprednisolone IV over 1 hour twice a day on days -3 to -1, and total lymphoid irradiation on day -1. On day 0, patients receive umbilical cord blood (UCB) infusion.

Patients with inborn errors of metabolism or inherited hematopoietic disorders receive oral busulfan every 6 hours on days -9 to -6, cyclophosphamide IV over 1 hour on days -5 to -2 or melphalan IV over 20 minutes on days -4 to -2, and ATG IV over 4 hours or methylprednisolone IV over 1 hour on days -3 to -1. On day 0, patients receive UCB infusion.

Patients with Fanconi's anemia receive ATG IV over 4 hours or methylprednisolone IV over 1 hour on days -6 to -1, cyclophosphamide IV over 1 hour on days -5 to -2, thoracoabdominal irradiation on day -1, and then the UCB infusion on day 0.

Patients also receive cyclosporine and methylprednisolone beginning on day -2 and continuing as necessary as graft-versus-host disease prophylaxis.

Patients are followed indefinitely for survival and late toxicity.

PROJECTED ACCRUAL: A total of 4-90 patients will be accrued for this study within 5 years.

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed diagnosis of one of the following: Severe aplastic anemia with bone marrow cellularity less than 20% and at least 2 of the following criteria: Granulocyte count less than 500/mm3; Platelet count less than 20,000/mm3; Reticulocyte count less than 50,000/mm3; Etiologies may be Fanconi's anemia, hypoplastic leukemia, monosomy 7, drug exposure (chloramphenicol, NSAIDS), viral exposure (EBV, hepatitis, parvovirus, HIV), nutritional deficiencies, thymoma, paroxysmal nocturnal hemoglobinuria, and amegakaryocytic thrombocytopenia; Myelodysplastic syndrome (MDS) that is refractory to medical management or with cytogenetic abnormalities predictive of transformation into acute leukemia, including 5q-, 7q-, monosomy 7, and trisomy 8; De novo primary or therapy-related secondary MDS; Refractory anemia or refractory anemia with ringed sideroblasts only; Inherited hematopoietic disorders that are refractory to medical management; Severe combined immunodeficiency; Familial erythrophagocytic lymphohistiocytosis; Wiskott-Aldrich syndrome; Kostmann's syndrome (infantile agranulocytosis); Chronic granulomatous disease; Leukocyte adhesion deficiency; Chediak-Higashi syndrome; Paroxysmal nocturnal hemoglobinuria; Fanconi's anemia; Dyskeratosis congenita; Diamond-Blackfan anemia; Amegakaryocytic thrombocytopenia; Osteopetrosis; Gaucher's disease; Lesch-Nyhan syndrome; Mucopolysaccharidoses; Lipidoses
• Must also meet all the following conditions: No HLA-ABC/DR identical related bone marrow or UCB donor; No 5/6 antigen matched related bone marrow or UCB donor; Condition precludes waiting to search and find a donor in the National Marrow Donor Registry
• Must have backup autologous or haploidentical related marrow
• Must have available serologic match umbilical cord blood unit in the New York Blood Center's Placental Blood Project

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No concurrent cytotoxic chemotherapy
• Endocrine therapy: No concurrent immunosuppressive medications
• Radiotherapy: No concurrent radiotherapy
• Surgery: Not specified

--Patient Characteristics--

• Age: Not specified
• Performance status: Zubrod 0-1 OR Karnofsky or Lansky 80-100%
• Life expectancy: At least 3 months
• Hematopoietic: See Disease Characteristics
• Hepatic: Bilirubin no greater than 2.0 mg/dL; ALT/AST no greater than 4 times normal
• Renal: Creatinine no greater than 2.0 mg/dL; Creatinine clearance at least 50 mL/min
• Cardiovascular: Shortening fraction or ejection fraction at least 80% of normal for age
• Pulmonary: FVC and FEV1 at least 60% predicted for age; Adults: DLCO at least 60% predicted
• Other: No active concurrent malignancy; No active infections at time of backup bone marrow harvest or pretransplant cytoreduction; Not pregnant or nursing; Negative pregnancy test; HIV negative

Florida
      Division of Pediatric Surgery, Jacksonville,  Florida,  32207,  United States
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612,  United States
      University of Florida Health Science Center, Gainesville,  Florida,  32610-0296,  United States
Illinois
      Rush-Presbyterian-St. Luke's Medical Center, Chicago,  Illinois,  60612,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637,  United States
Louisiana
      Children's Hospital of New Orleans, New Orleans,  Louisiana,  70118,  United States
Missouri
      Cardinal Glennon Children's Hospital, Saint Louis,  Missouri,  63104,  United States
New Jersey
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
New York
      New York Blood Center, New York,  New York,  10021,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States
North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
Pennsylvania
      St. Christopher's Hospital for Children, Philadelphia,  Pennsylvania,  19134-1095,  United States
South Carolina
      Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States
      University of South Carolina School of Medicine, Columbia,  South Carolina,  29203,  United States

Study chairs or principal investigators

Barbara Jean Bambach,  Study Chair,  Roswell Park Cancer Institute   

Study ID Numbers:  CDR0000066755; RPCI-RP-9803; NCI-G98-1486
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003662
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08