The goal of this clinical trial is to learn if photobiomodulation works to prevent severe oral mucositis in patients who are undergoing allogeneic hematopoietic cell transplantation. The main questions it aims to answer are:

Does 1) intraoral , 2) extraoral, or 3) combined intraoral/extraoral photobiomodulation have optimal prevention/therapeutic effect in prevention of oral mucositis in patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT).

Participants will:

Be randomized to one of the three treatment arms Receive daily photobiomodulation therapy (from beginning of transplant conditioning through Day +20 after transplantation) Be evaluated for oral mucositis and symptoms daily Visit the clinic once every 2 weeks for checkups and tests Keep a diary of their symptoms and the number of times they use a rescue inhaler

Patients who are planned for alloHSCT will be randomized 1:1:1 to one of the 3 treatment arms, stratified by age (<18, ≥ 18years). This is a phase 2 randomized trial to identify which of the three photobiomodulation therapy (PBMT) devices, 1) intraoral , 2) extraoral, and 3) combined intraoral/extraoral, has optimal prevention/therapeutic effect in prevention of oral mucositis in patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT). The study will be conducted in parallel, in a quasi-multi-center manner at three other alloHSCT centers (AC Camargo, SP, Brazil; Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Cincinnati Children's Hospital Medical Center; in addition to DFCI/BWH).

Participants will be evaluated daily according to the validated WHO Oral Toxicity Scale by trained and calibrated investigators. Within each arm, a Simon's 2 stage design will be applied in an intention to treat analysis of the proportion of patients who have <5 days of WHO grade ≥ 3 OM, to eliminate arms with insufficient evidence of efficacy. The remaining arms will be analyzed in a selection design (pick the winner) to determine the probability that the arm selected for a future phase 3 trial is either superior to, or at worst, more or less equivalent to, other arm(s). The study will enroll up to 96 patients with up to 26 patients per treatment arm. The accrual rate at DFCI is anticipated to be 2 patients/month, or 24 patients per year. The same accrual rate is anticipated at each of the other three study sites. Therefore, the total accrual of 78 patients can be achieved within 1 year.

The primary endpoint, duration of severe OM, is defined in section 11.1 as the total number of days between day 0 and day +20 on which severe (WHO grade 3 or 4) OM was reported. A conservative approach to missing data will be taken: Any day on which the grading of mucositis is missing will be counted as a day with WHO grade ≥3 OM. Each patient will be classified as either a success or a failure. "Success" will be defined as a patient who has a duration of WHO grade ≥3 OM <5 days; a patient with ≥5 days will be classified as a "failure" (i.e., a binary endpoint).

The secondary endpoints that will be subjectively considered in making the final selection of the winning arm are:

• Adverse events attributed to PBMT administration;
• Patient acceptability of the PBMT administration;
• Operator acceptability of the PBMT administration;
• Duration of time to complete PBMT administration;
• Duration of hospital stay; and,
• Need to initiate parenteral nutrition.

Inclusion Criteria:

• Planned to undergo myeloablative allogeneic HCT (with one of the following regimens): FluBu4, FluMel, or CyTBI conditioning and Tac-Mtx GVHD prophylaxis
• Age ≥4 years
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Participants who have had treatment with oral PBMT within four weeks of admission for HSCT.
• Participants who have a history of radiation therapy to the head and neck.
• Participants who have a history of photosensitivity or underlying disease with known photosensitivity.
• Participants who are planned to receive palifermin (keratinocyte growth factor) for OM prevention.
• Participants who have facial hair and unwilling to shave.