Abatacept as GVHD Prophylaxis Phase 2

Inclusion Criteria:

1. Must be at least 6 years old and weigh 20 kg.
2. Must have a willing unrelated adult donor (bone marrow or peripheral blood). Donors may have a single mismatch (i.e. be a 7/8) and this mismatch may be at the allele or antigen level; however, donors with allele level disparity should be given preference over those with antigen level disparity. The use of mismatched donors in which disparity is only in the host versus graft direction (because of recipient homozygosity) is discouraged because of the potentially heightened risk for graft rejection. Centers may perform extended typing (e.g. DQB1 and DPB1) according to institutional practices and use these results in selecting donors; however, it is recommended that this extending typing be used only to select between donors who are equally well matched with the recipient at the A, B, C and DRB1.
3. All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
4. Must have a high risk hematologic malignancy as defined below:

   1. Acute myeloid leukemia (AML).
   2. Myelodysplastic syndrome

   (i) Adult patients (≥21 years) must meet criteria for intermediate, high or very high-risk disease based on the World Health Organization classification based prognostic scoring system.

Intermediate risk (2 points), high risk (3-4 points), very high risk (4-5 points)

* RA = refractory anemia, RARS = refractory anemia with ringed sideroblasts, RCMD = refractory cytopenia with multilineage dysplasia, RCMD-RS = refractory cytopenia with multilineage dysplasia and ringed sideroblasts, RAEB-1 = refractory anemia with excess of blasts-1 (5-9% blasts), RAEB-2 = refractory anemia with excess of blasts-2 (10-19% blasts).
* \*Karyotype: Good = normal, -Y, del(5q), del(20q), Poor = complex (≥ 3 abnormalities), chromosome 7 anomalies, Intermediate = other abnormalities.

  * \*RBC transfusion requirement = having ≥ 1 RBC transfusion every 8 weeks over a 4-month period.

(ii) Pediatric patients with MDS, regardless of subtype, will be eligible.

(c) Acute lymphoblastic leukemia (ALL). (i) Given the poor prognosis of adults (≥21 years) with ALL, adults in 1st or greater complete remission will be eligible.. CR is defined as an M1 marrow (\<5% blasts), no evidence of extramedullary disease, and an absolute neutrophil count ≥ 1.0 x 109/L. Complete remissions without platelet recovery (CRp) will be considered remissions (ii) Given the generally good prognosis of children (\<21 years) with ALL, they will have to meet one of the criteria listed below. Additionally, children who are enrolled on a COG ALL trial for newly diagnosed or relapsed disease will have to meet the criteria for BMT outlined in that trial. CR is defined as an M1 marrow (\<5% blasts), no evidence of extramedullary disease, and an absolute neutrophil count ≥ 1.0 x 109/L. Complete remissions without platelet recovery (CRp) will be considered remissions.

1. In 1st complete remission with a very high risk for relapse.

   1. Haplodiploidy (\<44 chromosomes)
   2. \>1% residual marrow blasts by flow cytometry at the end of induction.
   3. \>0.01% residual marrow blasts by flow cytometry at the end of consolidation.
   4. Early T-Cell Precursor (ETP) phenotype
2. In 2nd complete remission with B-lineage disease after a marrow relapse occurring less than 36 months from diagnosis.
3. In 2nd complete remission with T-lineage disease or Ph+ disease after a marrow relapse occurring at any time.
4. In a 2nd complete remission with T-lineage disease after an extra-medullary relapse occurring less than 18 months from diagnosis.
5. In 3rd or greater complete remission after a marrow or extramedullary relapse

   (d) Patients with acute undifferentiated, biphenotypic, or bilineal leukemia, which is in 1st or greater complete remission (CR) or partial remission (PR). Cr will be defined as an M1 marrow (\<5% blasts), no evidence of extramedullary disease, and an absolute neutrophil count ≥ 1.0 x 109/L. CR without platelet recovery (CRp) will be considered complete remissions.) PR will be defined as an M2 marrow (5-19% blasts), no evidence of extramedullary disease, and an absolute neutrophil count ≥ 1.0 x 109/L.).

   (e) Chronic myelogenous leukemia (CML). (i) Chronic phase with resistance to tyrosine kinase inhibitors. (ii) accelerated phase (development of cytogenetic abnormality in addition to t(9:22), blood blast percentage ≥10, blood basophil percentage ≥20, platelet count \<100,000 X 109/L) (iii) blast crisis. (iv) 2nd or greater chronic phase.

   (f) Acute Lymphoblastic Lymphoma in 2nd or greater complete remission. Complete remission includes confirmed complete response (CR) defined as the disappearance of all evidence of disease from all sites for at least 4 weeks. Bone marrow and CSF must be normal and any macroscopic nodules in any organs detectable on imaging techniques should no longer be present. Imaging should include PET scanning. CR will also include unconfirmed complete responses defined as a residual lymph node mass \> 1.5 cm in greatest transverse diameter that has regressed by \> 75% in sum of the products of the greatest perpendicular diameters (SPD), or any residual lesions in organs that have decreased by \> 75%, with a negative PET scan, negative bone marrow and CSF.

   (g) Peripheral T cell lymphoma (PTCL).

   (h) Chronic lymphocytic leukemia (CLL) (i) Newly diagnosed disease with 17p- (ii) Disease beyond first CR that has been treated with a fludarabine containing regimen.

   (i) Chronic myelomonocytic leukemia.

   (j) Atypical (BCR-ABL negative) chronic myelogenous leukemia

   (k) Hodgkin lymphoma that has recurred or progressed after an autologous BMT. Disease must be chemosensitive; salvage chemotherapy must produce at least a partial response.

   (l) Non-Hodgkin lymphomas that has recurred or progressed after an autologous BMT.

Exclusion Criteria:

1. Prior allogeneic HSCT.
2. The patient is enrolled on a COG trial that uses criteria for unrelated donor HSCT, which conflict with our eligibility criteria.
3. The patient is enrolled on a COG trial that utilizes unrelated donor HSCT and requires that patients be transplanted using an approach specified by the protocol that is in conflict with the approach specified in this protocol.
4. Availability of a willing and suitable HLA identical related donor.
5. Uncontrolled viral, bacterial, fungal or protozoal infection at the time of study enrollment.
6. HIV infection.
7. Serious psychiatric disease including schizophrenia, bipolar disorder and severe depression.
8. Any patient with a known or suspected inherited predisposition to cancer should be discussed with the study team prior to screening for eligibility.

   1. Patients with a known inherited or constitutional predisposition to transplant morbidities, including, but not limited to Fanconi Anemia, Dyskeratosis Congenita, Shwachman-Diamond Syndrome and Down Syndrome will be excluded.
   2. Patients with known inherited or constitutional predisposition to non-hematologic cancers including, but not limited to Li-Fraumeni syndrome, BRCA1 and BRCA2 mutations will be excluded.
   3. Patients with an inherited predisposition to leukemia or otherwise hematologic malignancies that have not been associated with predisposition to transplant morbidities or non-hematologic cancers will not be excluded.
9. Known inherited or constitutional predisposition to cancer including, but not limited to Li-Fraumeni syndrome, Down syndrome and BRCA1 and BRCA2 mutations.
10. Incompletely treated active tuberculosis Infection.
11. Pregnancy (positive serum b-HCG) or breastfeeding.
12. Estimated GFR of \< 50 mL/min/1.73m2.
13. Cardiac ejection fraction \< 50.
14. bilirubin \> 2 × upper limit of normal or ALT \> 4 × upper limit of normal or unresolved veno-occlusive disease.
15. Pulmonary disease with FVC, FEV1 or DLCO parameters \<45% predicted (corrected for hemoglobin) or requiring supplemental oxygen. Children who are developmentally unable to perform pulmonary function testing will be assessed solely on their need for supplemental oxygen.
16. Karnofsky performance score or Lansky Play-Performance Scale score \<80
17. Presence of antibodies to a mismatched donor HLA antigen