IMRT-TMI With Fludarabine as Myeloablative Conditioning for Allogeneic HSCT

Inclusion Criteria:

1. Patients must be diagnosed with one of the following conditions:

   Acute Myeloid Leukemia (AML) who are not in complete remission, and who have either primary refractory or relapsed disease, and who do not have more than one of the following adverse factors:
   1. Duration of first CR \< 6 months (if previously in CR)
   2. Poor risk karyotype including any of the following: complex karyotype with ≥3 clonal abnormalities, 5q-/-5, 7q-/-7, 11q23 abnormalities, inv(3q), 20q or 21q abnormalities, t(6;9), t(9;22), 17p abnormalities \[or TP53 mutations\] or monosomal karyotype. Molecular typing (except for TP53 mutation) will not be used for eligibility criteria determination.
   3. Circulating peripheral blood blasts at time of enrollment
   4. Karnofsky performance status \<90%

   Acute Lymphocytic Leukemia (ALL) who are not in complete remission, and who have either primary refractory or relapsed disease, and who do not have more than one of the following adverse factors:
   1. First refractory relapse. Patients in second or subsequent relapse are excluded.
   2. Donor is CMV seropositive
   3. Bone marrow blasts \>25% (within 30 days of admission)
   4. Age \>40 years

   Myelodysplasia with a Revised International Prognostic Score (IPSS-R) of greater than 4.5 (i.e., high- or very-high risk).

   Chronic Myelogenous Leukemia (CML) in either
   1. Accelerated phase, defined by any of the following:

      * 10-19% blasts in peripheral blood white cells or bone marrow
      * Peripheral blood basophils at least 20%
      * Persistent thrombocytopenia (\<100 x 109/l) unrelated to therapy, or persistent thrombocytosis (\>1000 x 109/l) unresponsive to therapy
      * Increasing spleen size and increasing white blood cell (WBC) count unresponsive to therapy
      * Cytogenetic evidence of clonal evolution (i.e., the appearance of an additional genetic abnormality that was not present in the initial specimen at the time of diagnosis of chronic phase)
   2. Chronic phase provided a complete hematologic remission was not achieved by 3 months or a complete cytogenetic remission by 18 months and the patient had received at least 2 tyrosine kinase inhibitors.
2. Patient age 18-65 years old at time of consent
3. Availability of a consenting human leukocyte antigens(HLA) -matched donor
4. Karnofsky Performance Status 70% or higher
5. Required baseline laboratory values:

   1. Estimated creatinine clearance ≥ 60 ml/min
   2. Aspartate aminotransferase and alanine aminotransferease ≤ 2.5 x upper limit of normal value
   3. Bilirubin ≤ 1.5 x upper limit of normal value
6. Required baseline cardiac function of left ventricular ejection fraction (LVEF) \> 45

   * corrected
7. Required baseline pulmonary function of lung diffusing capacity (DLCO) \> 45 % predicted (corrected for hemoglobin)
8. Patient must be capable of understanding the investigational nature of this study, potential risks and benefits of the study, and be able to provide a valid informed consent.

Exclusion Criteria:

1. Patients with ALL who are in second or subsequent relapse
2. HIV seropositive patients.
3. Pregnant or nursing females are excluded from this study.
4. Prior radiation therapy
5. Patients who have had a prior autologous or allogeneic bone marrow or stem cell transplantation