Allogeneic Hematopoietic Stem Cell Transplant for GATA2 Mutations
United States144 participantsStarted 2013-07-24
Plain-language summary
Background:
\- GATA2 deficiency is a disease caused by mutations in the GATA2 gene. It can cause different types of leukemia and other diseases. Researchers want to see if a stem cell transplant can be used to treat this condition. A stem cell transplant will give stem cells from a matching donor (related or unrelated) to a recipient. It will allow the donor stem cells to produce healthy bone marrow and blood cells that will attack the recipient s cancer cells.
Objectives:
\- To see if stem cell transplants are successful at treating GATA2 mutations and related conditions.
Eligibility:
\- Recipients who are between 6 and 70 years of age and have GATA2 deficiency.
Design:
* All participants will be screened with a physical exam and medical history. Blood samples will be collected. Recipients will have imaging studies and other tests.
* Recipients will have chemotherapy or radiation to prepare for the transplant. On the day of the transplant, they will receive the donated stem cells.
* Recipients will stay in the hospital until their condition is stable after transplant.
* Frequent blood tests and scans will be required for the first 6 months after the transplant, followed by less frequent visits over time.
Who can participate
Age range6 Years – 70 Years
SexALL
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Inclusion criteria
✓. Patient age of 6-70 years.
✓. Mutation in the GATA2 gene, or evidence of loss of expression of one allele of GATA2, by cDNA analysis performed by a CLIA certified laboratory, or the clinical syndrome of MonoMAC.
✓. Clinical history of at least one serious or disfiguring infection and/or GATA2 bone marrow immunodeficiency disorder with lose of one or more immune populations in the bone marrow including monocytes, Natural Killer (NK) cells, and B-lymphocytes, with or without additional cytopenias involving the red blood cell, neutrophil, or platelet compartment.
✓. Availability of a 10/10 or 9/10 or 8/10 HLA-matched related or unrelated donor, or a haploidentical related donor.
✓. Patients may have evidence of MDS with one or more peripheral blood cytopenias and greater than 5% blasts but must have less than 10% blasts in the bone marrow in the absence of filgrastim in order to proceed directly to transplant. The majority of patients with MDS will have less than 5% blasts.
✓. Disease status: Patients are to be referred in remission for evaluation. Should a patient have progressive disease with \>10% blasts on screening/baseline bone marrow biopsy, the patient may receive standard treatment under the current study prior to proceeding with transplant. Once the patient has \<10% blasts, they may proceed to transplant. The patient may also be referred back to their primary hematologist or oncologist for treatment. If this course of action is not in the best interest of the patient according to the clinical judgment of the PI/LAI, then the patient may receive standard treatment for the malignant disease or hematological disorder under the current study. If under either of these settings, it becomes apparent that the participant will not be able to proceed to transplant, then he/she must come off study. Recipient-Subjects receiving a standard therapy will be told about the therapy, associated risks, benefits and alternatives of the proposed therapy, and availability of receiving the same treatment elsewhere, outside of a research protocol.
What they're measuring
1
To determine whether allogeneic HSCT approach results in engraftment and restores normal hematopoiesis by one year in patients with mutations GATA2.
✓. Left ventricular ejection fraction \> 40%, preferably by 2-D echocardiogram obtained within 90 days prior to initiation of conditioning therapy.
✓. Creatinine: Adult patients: \<= 2.0 mg/dl and creatinine clearance \>= 30 ml/min; Pediatric patients (\<18 years old): creatinine \<1.5 mg/dL and a creatinine clearance, using the Schwartz Formula, \> 30 mL/min/1.73m\^2.
Exclusion criteria
✕. Patients who are receiving any other investigational agents with the exception of virus- specific cytotoxic T-cells for the treatment of viral infection/reactivation prior to allo HSCT
✕. HIV-positive patients are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
✕. History of allergic reactions attributed to compounds of similar chemical or biological composition to agents (steroids, cyclophosphamide, busulfan) used in the study
✕. Chronic active hepatitis B. Patient may be hepatitis B core antibody positive. For patients with a concomitant positive hepatitis B surface antigen, patients will require a hepatology consultation. The risk-benefit profile of transplant and hepatitis B will be discussed with the patient, and eligibility determined by the PI or Lead Associate Investigator.
✕. History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent.
✕. Active infection refractory to antimicrobial therapy.
✕. Active CNS involvement by malignancy (patients with known positive CSF cytology or parenchymal lesions visible by prior CT or MRI).