Inclusion Criteria:

- Patients in 1st or 2nd remission with acute myeloid leukemia (AML) or acute
lymphoblastic leukemia (ALL) (no circulating blasts, < 5% myeloblasts in the bone
marrow, normalization of previously detected cytogenetic abnormalities, no
extramedullary disease )

- High risk myelodysplastic syndrome (MDS) (not myeloproliferative neoplasms)

- 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

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

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

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

- The effects of allogeneic transplantation on the developing fetus are highly toxic;
for this reason, 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 14 days from the start of
the conditioning regimen to confirm disease remission status

- Minimal residual disease will be assessed from pre-transplant and diagnostic (if
available) bone marrow aspirates by flow cytometry and Wilms' tumor suppressor gene
(WT1) polymerase chain reaction (PCR)

- 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 multiple gated angiogram (MUGA) > 50%

- Diffusion capacity of carbon monoxide (DLCO) or forced expiratory volume in 1 second
(FEV1) > 45% predicted

- Availability of an HLA matched (6/6) sibling donor or 8/8 matched unrelated donor (no
mismatch allowed in HLA-A, HLA-B, HLA-C and HLA-DR, donors with mismatch HLA-DQ or
HLA-DPH are eligible)

- All patients must have a psychosocial evaluation prior to transplant as per City of
Hope (COH) standard operating procedure (SOP)

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

- Patients who received chemotherapy (induction or consolidation) can proceed to
transplant once their counts have recovered (absolute neutrophil count [ANC] > 1000,
platelets > 100,000)

Exclusion Criteria:

- Patients who have received a prior autologous or allogeneic transplant are excluded

- Patients with significant hepatic dysfunction (not meeting liver function tests [LFT]
eligibility criteria in inclusion criteria)

- Patients with myelofibrosis or AML evolved from myelofibrosis

- Patients with MDS evolved into AML that is not in remission

- Patients with acute promyelocytic leukemia

- Patients with myeloproliferative neoplasms

- Patients with suspected or proven central nervous system (CNS) leukemia (diagnostic
lumbar puncture not required before enrollment)

- Uncontrolled intercurrent illness including, but not limited to ongoing or active or
poorly controlled infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, poorly controlled pulmonary disease or psychiatric
illness/social situations that would limit compliance with study requirements

- Pregnant or lactating women are excluded from this study

- Patients with immune deficiency are at increased risk of lethal infections when
treated with marrow-suppressive therapy; therefore, human immunodeficiency virus
(HIV)-positive patients are excluded from this study

- Patients who have received radiation therapy as part of their leukemia treatment may
be ineligible and individual cases must be presented to the 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

- Known allergies to clofarabine, melphalan, sirolimus or tacrolimus

- Patients with other active malignancies (besides AML, ALL, MDS) requiring treatment
or where there is concern of progression are ineligible for this study; however,
patients with previously treated skin cancer, early stage cervical or prostate cancer
may be eligible if there is no evidence of residual disease

- 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