Unrelated Umbilical Cord Blood Transplantation for Severe Aplastic Anemia and Hypo-plastic MDS Using CordIn, Umbilical Cord Blood-Derived Ex Vivo Expanded Stem and Progenitor Cells, to Expedite Engraftment and Improve Transplant Outcome
Background: Severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) are bone marrow diseases. People with these diseases usually need a bone marrow transplant. Researchers are testing ways to make stem cell transplant safer and more effective.
Objective: To test if treating people with SAA or MDS with a co-infusion of blood stem cells from a family member and cord blood stem cells from an unrelated donor is safe and effective.
Eligibility: Recipients ages 4-60 with SAA or MDS Donors ages 4-75
Design: Recipients will be screened with: * Blood, lung, and heart tests * Bone marrow biopsy * CT scan Recipients will have an IV line placed into a vein in the neck. Starting 11 days before the transplant they will have several chemotherapy infusions and 1 30-minute radiation dose. Recipients will get the donor cells through the IV line. They will stay in the hospital 3-4 weeks. After discharge, they will have visits: * First 3-4 months: 1-2 times weekly * Then every 6 months for 5 years Donors will be screened with: * Physical exam * Medical history * Blood tests Donors veins will be checked for suitability for stem cell collection. They may need an IV line to be placed in a thigh vein. Donors will get Filgrastim or biosimilar (G-CSF) injections daily for 5-7 days. On the last day, they will have apheresis: Blood drawn from one arm or leg runs through a machine and into the other arm or leg. This may be repeated 2 days or 2-4 weeks later.
⁃ Diagnosed with severe aplastic anemia with bone marrow cellularity \<30% (excluding lymphocytes) associated with RBC or platelet transfusion dependence and/or neutropenia (absolute neutrophil count \<=1000 cells/ uL or for patients receiving granulocyte transfusions, absolute neutrophil count \<=1000 cells/ uL before beginning granulocyte transfusions).
⁃ OR
⁃ History of severe aplastic anemia transformed to MDS that meet the following criteria: a) International Prognostic Scoring System (IPSS) risk category of INT-1 or greater, b) \< 5% myeloblasts and \< 30% of cellularity in the bone marrow on screening morphologic analysis.
• Intolerance of or failure to respond to standard immunosuppressive therapy.
⁃ Identification of either a) at least one alternative donor (i.e. HLA- haploidentical related donor (i.e. \>=5/10 HLA match: HLA-A, B, C, DR, and DQ loci) or \>=9/10 HLA matched unrelated donor) who is available to serve as a stem cell donor for a salvage allogeneic transplant in the event that the CordIn(TM) unit has been rejected or b) umbilical cord blood unit/s that can be used for a salvage cord blood transplant in the event that the CordIn(TM) unit has been rejected.
• Availability of at least one \>=4/8 HLA matched (HLA-A, B, C, and DR loci) cord blood unit from the National Marrow Donor Program (NMDP).
⁃ The cord blood unit must contain a minimum TNC of at least 1.8 x 10\^9 and at least 1.5x10\^7/kg TNC and at least 8 x 10\^6 CD34+ cells (all doses prior to thawing).
⁃ Exception: Cord units containing at least 8 x 10\^6 CD34+ cells but less than 1.8 x 10\^9 TNC may be eligible for use on this trial if
‣ the pre-expansion CD34/kg recipient cell number is at least 1.5 x 10\^5 /kg
‣ AND
‣ approval for use of this cord unit for expansion is granted by Gamida Cell.
‣ the final cell counts on the cultured and non-cultured fractions meet the IND specified minimal release criteria.
• The CBU will have undergone volume reduction (both plasma and red blood cell depletion) prior to cryopreservation. All CBUs should be procured from public banks that meet local applicable regulations.
∙ Ages 4-60 years inclusive.
∙ Ability to comprehend the investigational nature of the study and provide informed consent. The procedure will be explained to subjects aged 4-17 years with formal consent being obtained from parents or legal guardian.