Campath/Fludarabine/Melphalan Transplant Conditioning for Non-Malignant Diseases

A Study of Hematopoietic Stem Cell Transplantation (HSCT) in Non-Malignant Disease Using a Reduced-Intensity Preparatory Regime

The hypothesis for this study is that a preparative regimen that maximizes host immunosuppression without myeloablation will be well tolerated and sufficient for engraftment of donor hematopoietic cells. It is also to determine major toxicities from these conditioning regimens, within the first 100 days after transplantation.

The study uses reduced intensity conditioning that is immune suppressive to achieve donor cell engraftment without exposure to radiation or high dose chemotherapy in children with non-malignant disorders. The intent is to minimize early and late regimen related toxicities in the context of a reduced intensity regimen.

In addition to maximizing opportunity for donor cell engraftment, the trial seeks to minimize toxicities associated with transplant such as graft versus host disease and employs GVHD prophylaxis that seeks to decrease rates of acute and chronic GVHD in the setting of matched and mismatched donor stem cell transplants from marrow and cord blood sources.

Inclusion Criteria:

Stratum 1: Patient must have non-malignant disorder, excluding thalassemia. Must be receiving a 8/8 HLA-matched bone marrow, related or unrelated Stratum 2: Patient must have thalassemia receiving 8/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated.

Stratum 3: Patient must have a hemoglobinopathy receiving 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated.

Stratum 4: Patient must have a non-malignant disorder (excluding hemoglobinopathy) receiving 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated.

All strata:

• Recipient age < 21 years
• Lansky/Karnofsky >/= 40
• Adequate pulmonary, renal, liver, and other organ function as defined in protocol
• Negative pregnancy test
• Adequate total nucleated cell or CD34+ dose of product as defined in protocol
• If sickle cell, Hemoglobin S <30%

Exclusion Criteria:

• HIV positive
• Invasive infection
• Pregnancy/lactating