A Pilot Study to Evaluate the Feasibility of Post-Hematopoietic Stem Cell Transplant Prophylaxis With Decitabine Combined With Filgrastim for Children and Young Adults With AML, MDS and Related Myeloid Malignancies (MORE)

Inclusion Criteria: Disease Criteria: Participants must have a histologically confirmed diagnosis of one of the following hematologic malignancies for eligibility, as defined by the criteria below: AML (relapsed, de-novo or secondary) based on WHO classification MDS (relapsed, de-novo or secondary) based on WHO classification Treatment myeloid neoplasm (tMDS/AML; relapsed disease included) Note: MDS, AML, MDS/AML, or tMDS/AML as defined above may be idiopathic/de novo or derived from a germline predisposition to myeloid malignancy. For patients with an underlying germline disorder, those conditions that are not associated with increased risk for toxicity to treatment, including patients with known germline ANKRD26, DDX41, ELANE and other congenital neutropenia disorders, ETV6, GATA-2, Li-Fraumeni, RUNX1, SAMD9/SAMD9L, or Shwachman-Diamond Syndrome, will be analyzed within the general treatment cohort (Cohort A, see Table 1) along with patients with idiopathic disease (Cohort B, see Table 2). MDS, AML, MDS/AML, or tMDS/AML derived from the following germline disorders will be enrolled in a separate cohort (B) and adverse events monitored closely for higher rates compared to cohort A: Dyskeratosis Congenita or associated telomeropathies as defined by telomere length <1st percentile on 3 out of 4 lymphocyte subsets and/or corresponding pathogenic genetic mutation. Fanconi Anemia as defined by positive chromosomal breakage test to DEB/MMC and/or corresponding pathogenic genetic mutation. Nijmegen Breakage Syndrome as defined by positive chromosomal breakage test to DEB/MMC and/or corresponding pathogenic genetic mutation ERCC6L2 by genomic testing. Table 2: Overview Inherited Bone Marrow Failure syndromes (iBMF) -iBMF with Standard risk for Treatment Related toxicities: germline mutations in ANKRD26 germline mutations in DDX41 ELANE and other Congenital Neutropenia Disorders germline mutations in ETV6 germline mutations in GATA-2 Li-Fraumeni germline mutations in RUNX1 SAMD9/SAMD9L Shwachman-Diamond Syndrome Familial MDS with thrombocytopenia Diamond-Blackfan Anemia Table 2: Overview Inherited Bone Marrow Failure syndromes (iBMF) iBMF with Increased Risk for Treatment Related Toxicities: Fanconi Anemia Dyskeratosis Congenita and associated Telomere Disorders Nijmegen Breakage Syndrome ERCC6L2 Patients must be receiving an allogeneic hematopoietic stem cell transplant. All donor types and graft sources are permitted. All conditioning regimens are permitted. All GVHD prophylaxis regimens are permitted. Timing of Enrollment: Registration can occur from day - 30 to day - 10 prior to stem cell infusion. Disease Status: Study enrollment will occur pre HCT. Any disease status is acceptable at the time of enrollment; however, patients must be in a MRD negative remission (as defined by multidimensional flow cytometry (MDF) post HCT prior to protocol treatment start). Post HCT/ pretreatment disease status will be performed by Hematologics. No limitations on prior therapy. Age ≥1 year and ≤ 39 year of age. ECOG performance status ≤2 (Lansky, Karnofsky ≥60%). Participants must have adequate organ function to be eligible for allogenic HCT as per institutional standard. Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Anti- retroviral therapy must not have a non-acceptable drug interaction with protocol treatment. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Suppressive therapy must not have a non-acceptable drug interaction with protocol treatment. Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Ongoing antiviral therapy must not have a non-acceptable drug interaction with protocol treatment. Participants with a malignancy in remission are eligible for this trial. Participants with known history or current symptoms of cardiac disease should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better. The effects of filgrastim on the developing human fetus are unknown. For this reason and because decitabine is known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of decitabine administration. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 2) except for bone marrow suppression. Participants should not be enrolled on another study that prohibits initiation of maintenance therapy. History of allergic reactions attributed to compounds of similar chemical or biologic composition to decitabine or filgrastim. Participants with uncontrolled intercurrent illness. Participant who are not able to present for clinic visits for at least 7 months after study treatment initiation. Participant with FLT3/ITD mutations are excluded as maintenance therapy with tyrosine kinase therapy should be considered in this context. Participants with a concurrent active malignancy are not eligible for this trial.