Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia

Patients in 1st or 2nd remission with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), who are eligible for stem cell transplant. Remission defined as no circulating blasts, \< 5% blasts in the bone marrow, normalization of previously detected cytogenetic abnormalities, no extramedullary disease

High risk myelodysplastic syndrome (MDS)

* Intermediate II and high risk by International Prognostic Scoring System (IPSS)

* Intermediate, high, or very high by World Health Organization (WHO) classification-based Prognostic Scoring System (WPSS)

* Transfusion dependent

* Therapy-related MDS or MDS evolved from previous hematological disorder (excepting myelofibrosis)

Patients with chronic myelomonocytic leukemia (CMML) are allowed to be enrolled

Patients with MDS that has evolved to AML must be in remission

Patients must not be eligible for full ablative regimens by the attending physician

Patients with AML or MDS arising from myeloproliferative neoplasm can be enrolled after principal investigator (PI) approval on case to case basis, depends on the spleen size and degree of bone marrow fibrosis

Performance status of \>= 70% on the Karnofsky scale

Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect she is pregnant while participating on the trial, she should inform her treating physician immediately

Bone marrow and peripheral blood studies must be available for confirmation of diagnosis; cytogenetics, flow cytometry, and molecular studies (such as Flt-3 status) will be obtained as per standard practice

Bone marrow aspirates/biopsies should be performed within 28 (+ 4 day window) days from registration to confirm disease remission status

A pretreatment measured creatinine clearance (absolute value) of \>= 60 mL/minute

Patients must have a serum bilirubin =\< 2.0 mg/dl

Patients must have serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =\< 2.5 times the institutional upper limit of normal

Ejection fraction measured by echocardiogram or multi gated acquisition scan (MUGA) \> 50%

Diffusing capacity of the lung for carbon monoxide (DLCO) or forced expiratory volume in 1 second (FEV1) \> 45% predicted

Availability of a human leukocyte antigen (HLA) matched (6/6) sibling donor or 8/8 matched unrelated donor; Donors with mismatch at HLA-A, HLA-B, HLA-C, and HLA-DR will be reviewed by matched unrelated donor (MUD) committee and allowed if their mismatch with the recipient does not require additional GVHD prophylaxis (other than tacrolimus and sirolimus), donors with mismatch at HLA-DQ or HLA-DPB are eligible; donor evaluation according to City of Hope (COH) standard operating procedure (SOP)

Donor stem cell source can be either peripheral blood or bone marrow

All patients must have a psychosocial evaluation prior to transplant as per COH SOP

All subjects must have the ability to understand and the willingness to sign a written informed consent

ALL or AML patients who received chemotherapy (induction or consolidation) can proceed to transplant once bone marrow cellularity is \> 10 % with no evidence of leukemia

Patients who have received radiation therapy as part of their leukemia treatment may be ineligible and individual cases must be presented to the study principal investigator (PI) for determination of eligibility

Any psychiatric, social or compliance issues that, in the treating physician's opinion, will interfere with completion of the transplant treatment and follow up

Medical or psychiatric reasons which make the donor unlikely to tolerate or cooperate with filgrastim (G-CSF) therapy or leukapheresis or bone marrow harvest

Known allergies to clofarabine, melphalan, sirolimus or tacrolimus

Cord blood as a donor source is not acceptable

Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

What this study is about