Inclusion Criteria:

• Willing and able to provide written informed consent.
• Males or females, ≥ 18 years of age.
• Receiving a human leukocyte antigen (HLA) matched allogeneic peripheral BMT from a family or unrelated donor, HLA-mismatched related or unrelated donor, or haploidentical donor.
• Diagnosed with 1 of the following underlying diseases:
  • Refractory anemia;
  • Refractory anemia with ringed sideroblasts;
  • Refractory cytopenia with multilineage dysplasia;
  • Refractory cytopenia with multilineage dysplasia and ringed sideroblasts;
  • Refractory anemia with excess blasts - 1 (5-10% blasts);
  • Refractory anemia with excess blasts - 2 (10-20% blasts);
  • Myelodysplastic syndrome, unclassified;
  • Myelodysplastic syndrome associated with isolated del (5q);
  • Chronic myelomonocytic leukemia;
  • Lymphoma (including Hodgkin's) with chemosensitive disease (i.e., response to chemotherapy) and receiving a related donor transplant;
  • Aplastic anemia;
  • Primary or secondary myelofibrosis.
• Acute myeloid leukemia (AML), with or without a history of myelodysplastic syndrome, in first or second complete remission.
• Acute lymphoblastic leukemia, in first or second complete remission.
• Acute undifferentiated leukemia in first or second remission.
• Acute biphenotypic leukemia in first or second complete remission.
• Chronic myelogenous leukemia in either chronic or accelerated phase.
• One of the following myelodysplastic syndrome(s) defined by the following:
  • Receiving myeloablative or reduced-intensity conditioning regimens.
• Adequate renal and hepatic function, within 6 weeks of initiation of conditioning, as measured by:
  • Hepatic (within 72 hours of Day 0): alanine aminotransferase;
  • Renal (within 72 hours of Day 0): Serum creatinine within normal range for age or if serum creatinine above ULN range for age, a creatinine clearance [CrCl]) ≥60 mL/min.;
  • Baseline blood samples drawn for serum Platelia galactomannan enzyme immunoassay (GM EIA) and β-D glucan levels within 14 days before randomization, with results available prior to randomization;
  • Baseline Toxoplasma serologies available within 6 weeks prior to randomization;
  • Baseline glucose-6-phosphate dehydrogenase (G6PD) deficiency testing with no evidence of G6PD deficiency performed within 6 weeks prior to randomization.
• Female subjects of child-bearing potential < 2 years post-menopausal must agree to and comply with using 1 barrier method (e.g., female condom with spermicide) plus one other highly effective method of birth control (e.g., oral contraceptive, implant, injectable, indwelling intrauterine device, vasectomized partner), or sexual abstinence while participating in this study. Male subjects must be vasectomized, abstain from sexual intercourse, agree to use barrier contraception (condom with spermicide), and also agree not to donate sperm while participating in the study and for 120 days from the last IV dose of study drug.

Exclusion Criteria:

• Diagnosis of AML not in morphological remission.
• Diagnosis of chemotherapy-resistant lymphoma.
• Suspected or diagnosed invasive fungal disease (IFD) within 4 weeks of screening.
• Diagnosed symptomatic heart failure with left ventricular ejection fraction (LVEF) at rest ≤ 40%, LVEF > 40% but fails to improve with exercise, or shortening fraction ≤ 26%.
• Personal or family history of Long QT interval on ECG (QT) syndrome or a prolonged QT interval corrected (QTc) interval (> 470 msec in males and > 480 msec in females); or concurrent administration of terfenadine, cisapride, astemizole, erythromycin, pimozide, or quinidine.
• Diagnosed reduced lung function with either diffusion capacity (corrected for hemoglobin), forced expiratory volume 1, forced vital capacity ≤ 45% of predicted value, or O2 saturation ≤ 85% on room air.
• Suspected or documented PCP within 2 years of screening.
• Positive baseline serum Platelia GM EIA (≥ 0.5) and/or β-D glucan assay (≥ 80 pg/mL).
• Receipt of previous allogeneic BMT.
• Planned receipt of cord blood for transplantation.
• Planned peripheral blood or marrow autograft.
• Underlying diagnosis of multiple myeloma.
• Grade 2 or higher ataxia, tremor, motor neuropathy, or sensory neuropathy, per NCI CTCAE version 5.0.
• History of severe ataxia, neuropathy or tremors; or a diagnosis of multiple sclerosis or a movement disorder (including Parkinson's disease or Huntington's disease).
• Planned or ongoing therapy at screening with a known neurotoxic medication for a complete list of prohibited neurotoxic medications).
• Known hypersensitivity to Rezafungin for Injection, any echinocandin, fluconazole, posaconazole, other azole antifungal, or to any of their excipients.
• Known hypersensitivity or inability to receive TMP/SMX or any of its excipients.
• Recent use of an investigational medicinal product within 28 days of the first dose of prophylactic study drug or presence of an investigational device at the time of screening.
• Known infection with HIV.
• Pregnant or lactating females.
• The Principal Investigator (PI) determines that the subject should not participate in the study.
• Considered unlikely to follow up for 90 days after receipt of the BMT due to logistic concerns (i.e., location relative to transplant center).

Eligibility last updated 10/5/21. Questions regarding updates should be directed to the study team contact.