TAC/MTX vs. TAC/MMF/PTCY for Prevention of Graft-versus-Host Disease and Microbiome and Immune Reconstitution Study (BMT CTN 1703/1801)

Phase 3

Completed

Conditions: Myelodysplasia
Lymphoma
Acute Leukemia
Chronic Myelogenous Leukemia (CML)

Interventions: Procedure: Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate
Procedure: Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide
Drug: Tacrolimus
Drug: Methotrexate
Drug: Mycophenolate Mofetil
Drug: Cyclophosphamide

Registration Number: NCT03959241

Lead Sponsor: Medical College of Wisconsin

Brief Summary: 1703: The study is designed as a randomized, phase III, multicenter trial comparing two acute graft-versus-host disease (aGVHD) prophylaxis regimens: tacrolimus/methotrexate (Tac/MTX) versus post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) in the setting of reduced intensity conditioning (RIC) allogeneic peripheral blood stem cell (PBSC) transplantation.

1801: The goal of this protocol is to test the primary hypothesis that the engraftment stool microbiome diversity predicts one-year non-relapse mortality in patients undergoing reduced intensity allogeneic HCT.

Detailed Description: 1703: Graft-versus-Host Disease (GVHD) is a complication that affects many hematopoietic stem cell transplant (HSCT) patients; it occurs when the new cells from a transplant attack the recipient's body. The current standard GVHD prophylaxis regimen for patients with hematologic malignancies undergoing HSCT involves a combination of immunosuppressive agents given for the first 6 months after transplant.

The standard strategy of Tacrolimus/Methotrexate will be used as a control arm in comparison to one other treatment plan utilizing Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide. Study participants will receive an infusion of mobilized peripheral blood stem cell grafts on both arms. Study participants will be randomized to one of these two treatment arms.

1801: A relationship between the intestinal microbiota and graft-versus-host disease (GVHD) has long been appreciated but is still not well understood. Mice transplanted in germ-free conditions or treated with gut-decontaminating antibiotics developed less severe GVHD. Clinical studies initially suggested a benefit from near-total bacterial decontamination, but later showed no clear benefit and this approach was discontinued in the early 1990s. Partial gut decontamination continues to be practiced at many centers. More recently, the advent of next-generation sequencing (NGS) has resulted in cheaper and easier characterization of complex microbial mixtures. This has led to a renewed interest in evaluating the relationship between the microbiota and human health and disease, including recipients of hematopoietic cell transplantation (HCT). Similarly, NGS has also contributed to significant advancements in the investigator's understanding of immune reconstitution in HCT patients and how this may impact clinica outcomes.

The goal of this protocol is to test the primary hypothesis that the engraftment stool microbiome diversity predicts one-year non-relapse mortality in patients undergoing reduced intensity allogeneic HCT.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 431

Inclusion Criteria

Age 18.0 years or older at the time of enrollment on Segment A
Patients with acute leukemia or chronic myelogenous leukemia with no circulating blasts and with less than 5% blasts in the bone marrow
Patients with myelodysplasia/chronic myelomonocytic leukemia with no circulating blasts and with less than 10% blasts in the bone marrow (higher blast percentage allowed in MDS due to lack of differences in outcomes with <5% vs. 5-10% blasts in this disease)
Patients with relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma with chemosensitive disease at time of transplantation
Patients with lymphoma [follicular lymphoma, Hodgkin lymphoma, diffuse large B cell lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and anaplastic large cell lymphoma] with chemosensitive disease at the time of transplantation
Planned reduced intensity conditioning regimen (see eligible regimens in Table 2.4a)
Patients must have a related or unrelated peripheral blood stem cell donor as follows:
1. Sibling donor must be a 6/6 match for Human Leukocyte Antigen-A (HLA)-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing, and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation.
2. Unrelated donor must be a 7/8 or 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donor must be willing to donate peripheral blood stem cells and meet National Marrow Donor Program (NMDP) criteria for donation.
Cardiac function: Left ventricular ejection fraction at least 45%
Estimated creatinine clearance acceptable per institutional guidelines
Pulmonary function: Diffusing capacity of lung for carbon monoxide (DLCO) corrected for hemoglobin at least 40% and forced expiratory volume at one second (FEV1) predicted at least 50%
Liver function acceptable per institutional guidelines
Karnofsky Performance Score at least 60%
Female patients (unless postmenopausal for at least 1 year before the screening visit, or surgically sterilized), agree to practice two (2) effective methods of contraception at the same time, or agree to completely abstain from heterosexual intercourse, from the time of signing the informed consent through 12 months post-transplant (see Section 2.6.4 for definition of postmenopausal)
Male patients (even if surgically sterilized), of partners of women of childbearing potential must agree to one of the following: practice effective barrier contraception (see Section 2.6.4 for list of barrier methods), or abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant
Plans for the use of post-transplant maintenance therapy must be disclosed upon enrollment and must be used irrespective of the outcome of the randomization. Please note that THIS DOES NOT INCLUDE INVESTIGATIONAL AGENTS and maintenance therapy with investigational treatment requires approval by the study chairs.
Voluntary written consent obtained prior to the performance of any study-related procedure that is not a part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

Exclusion Criteria

Prior allogeneic transplant
Active central nervous system (CNS) involvement by malignant cells
Patients with secondary acute myeloid leukemia arising from myeloproliferative disease, including chronic myelomonocytic leukemia (CMML)
Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
Presence of clinically significant fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated
Patients seropositive for human immunodeficiency virus (HIV) with detectable viral load. HIV+ patients with an undetectable viral load on antiviral therapy are eligible.
Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia.
Female patients who are pregnant (as per institutional practice) or lactating
Patients with a serious medical or psychiatric illness likely to interfere with participation in this clinical study
Patients with prior malignancies except resected non-melanoma skin cancer or treated cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent < 5 years previously must be reviewed and approved by the Protocol Officer or Chairs.
Planned use of antithymocyte globulin (ATG) or alemtuzumab in conditioning regimen

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tacrolimus/Methotrexate	Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate	Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate
Tacrolimus/MMF/PTCY	Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide	Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide
Tacrolimus/Methotrexate	Methotrexate	Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate
Tacrolimus/Methotrexate	Tacrolimus	Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate
Tacrolimus/MMF/PTCY	Mycophenolate Mofetil	Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide
Tacrolimus/MMF/PTCY	Tacrolimus	Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide
Tacrolimus/MMF/PTCY	Cyclophosphamide	Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With GVHD/Relapse or Progression-free Survival (GRFS) at One Year	1 year post randomization	The primary endpoint is GRFS as a time to event endpoint from randomization. All randomized patients will be followed for one year; however, the primary endpoint will be analyzed as a time to event endpoint. The primary analysis will be done using the randomized population. An event for this time to event outcome is defined as grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, disease relapse or progression, or death by any cause, whichever comes first. Time to event analyses were conducted. An unadjusted Kaplan-Meier analysis was done. Additionally, a multivariate Cox regression model adjusting for the following pre-specified covariates: age group (\< 65 vs. 65+), disease risk index (low, intermediate, high/very high), planned RIC conditioning regimen (Fludarabine/Busulfan, Fludarabine/Melphalan, Other), donor type/HLA matching score (related 6/6, unrelated 7/8, unrelated 8/8), and planned use of post-transplant maintenance therapy (Yes vs. no).

Secondary Outcome Measures

Name	Time	Method
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant	Day 100 post-transplant	Organ stages were graded according to Mount Sinai Acute GVHD International Consortium (MAGIC) Criteria (Harris et al. 2016). Higher stage in any organ indicates worse outcomes. For skin, stage 0-no GVHD rash; 1-Maculopapular Rash \<25% BSA; 2-Maculopapular Rash 25-50% BSA; 3-Maculopapular Rash \>50% BSA; 4-Generalized Erythroderma Plus Bullous Formation and Desquamation \>5% BSA. For Lower GI, 0-No Diarrhea or Diarrhea-Adult: \<500 mL/day, \<3 Episodes/day; Child: \<10 mL/kg/day, \<4 Episodes/day; 1-Diarrhea-Adult: 500-999 mL/day, 3-4 Episodes/day; Child: 10-19.9 mL/kg/day, 4-6 Episodes/day; 2-Diarrhea-Adult: 1000-1500 mL/day, 5-7 Episodes/day; Child: 20-30 mL/kg/day, 7-10 Episodes/day; 3-Diarrhea-Adult: \>1500 mL/day, \>7 Episodes/day; Child: \>30 mL/kg/day, \>10 Episodes/day; 4-Severe Abdominal Pain With or Without Ileus or Grossly Bloody Stool. For liver, 0-Bilirubin \<2.0 mg/dL; 1-Bilirubin 2.0-3.0 mg/dL; 2-Bilirubin 3.1-6.0 mg/dL; 3-Bilirubin 6.1-15.0 mg/dL; 4-Bilirubin \>15.0 mg/dL
Frequencies of Infections Categorized by Infection Type	1 year post-transplant	All Grade 2 and 3 infections were reported according to the BMT CTN Technical Manual of Procedures (MOP) up to 1 year post-transplant. The frequency of Grade 2-3 infections and the number of participants experiencing infections occurring within 1 year post-transplant, are tabulated by treatment arm, organism, time period of infection onset, and severity, with Grade defined per the BMT CTN Technical MOP.
Percentage of Participants With Grades II-IV and III-IV Acute GVHD at Day 100 Post-transplant	Days 100 post-transplant	Acute GVHD was graded according to Mount Sinai aGVHD International Consortium (MAGIC) Criteria (Harris et al. 2016) with higher grade indicating worse outcomes. Grade I aGVHD is defined as Skin stage 1-2 and stage 0 for both GI and liver. Grade II is stage 3 skin, stage 1 GI, or stage 1 liver. Grade III is stage 2-3 GI or stage 2-3 liver. Grade IV is stage 4 skin or stage 4 liver. The cumulative incidence of acute GVHD grade II-IV and III-IV at Day 100 was estimated using the Aalen-Johansen estimator with 95% confidence intervals, treating death prior to aGVHD as a competing event. The cumulative incidences of Minnesota standard and high risk aGVHD at Day 100 were determined with 95% confidence intervals. Time to aGVHD is defined as time from transplant until onset of grades II-IV and III-IV aGVHD, respectively. A multivariate Cox regression model was used to compare the treatment groups, with adjustment for same baseline characteristics as for the primary endpoint.
Participants With Maximum Stage of Upper GI at Day 100 Post-transplant	Day 100 post-transplant	Organ stages were graded according to Mount Sinai Acute GVHD International Consortium (MAGIC) Criteria (Harris et al. 2016). Higher stage in any organ indicates worse outcomes. For upper GI, stage 0 is no or intermittent nausea, vomiting, or anorexia; stage 1 is persistent nausea, vomiting, or anorexia. The maximum stages of Upper GI at patient level were summarized at Day 100.
Number of Participants Experiencing Chronic GVHD With Maximum Severity at 12 Months Post-transplant	12 months post-transplant	Chronic GVHD data were collected directly from providers and chart review as defined by the NIH Consensus Conference Criteria. Eight organs were scored on a 0-3 scale to reflect degree of chronic GVHD involvement per the NIH global severity scores of mild, moderate and severe chronic GVHD. The maximum severity of chronic GVHD through 12 months post-transplant will be tabulated by treatment arm.
Percentage of Participants With Lymphocyte Recovery Post-transplant	Day 60, Day 100, 6 Months, and 1 year post-transplant	Lymphocyte recovery is defined as the first day of sustained absolute lymphocyte count greater than or equal to 1000/mm\^3. The competing event is death without lymphocyte recovery. The cumulative incidence estimate of Lymphocyte recovery were described by treatment group with 95% confidence intervals (complementary log-log transformation), treating death as a competing event.
Percentage of Participants With Disease Relapse at 1 Year Post-transplant	1 year post-transplant	Disease relapse/progression is defined as being alive and free of relapse/progression of the primary disease. The time from transplant until relapse/progression of the primary disease, or cumulative incidence, was estimated at one-year post-transplant along with 95% CIs computed using the complementary log-log transformation, treating death prior to disease relapse as a competing event. A multivariate Cox regression model for the cause-specific hazard of relapse or progression will be used to compare the treatment groups, after adjustment for baseline characteristics as described for the primary endpoint.
Participants With Maximum Acute GVHD at One Year Post-transplant	One year post-transplant	Acute GVHD were graded according to Mount Sinai Acute GVHD International Consortium (MAGIC) Criteria (Harris et al. Biology of Blood and Marrow Transplantation 2016; 22:4-10). The higher acute GVHD grade indicates worse outcomes. Grade 0 is no acute GVHD of any organ. Grade I acute GVHD is defined as Skin stage of 1-2 and stage 0 for both GI and liver organs. Grade II is stage 3 of skin, or stage 1 of GI, or stage 1 of liver. Grade III is stage 2-3 for GI, or stage 2-3 of liver. Grade IV is stage 4 of skin, or stage 4 of liver. Max acute GVHD by one-year post-transplant was computed.
Percentage of Participants With Platelet Recovery Post-transplant	Day 60 and Day 100 post-transplant	Platelet recovery is defined by two different metrics: the first day of a sustained platelet count greater than or equal to 20,000/mm\^3 or greater than or equal to 50,000/mm\^3 with no platelet transfusions in the preceding seven days. The first day of sustained platelet count above these thresholds will be designated the day of platelet engraftment. For participants who never drop their platelet count below 20,000/mm\^3 or 50,000/mm\^3, the date of platelet recovery will be Day +1 post HCT. The competing event is death without platelet recovery. The cumulative incidence estimate of platelet recovery by Day 60 and Day 100 were described by treatment group with 95% confidence intervals (complementary log-log transformation), treating death as a competing event.
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant	1 year post-transplant	All Grade 3-5 toxicities will be tabulated by grade for each randomized treatment arm, by type of toxicity as well as the peak grade overall. Toxicities were evaluated using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Percentage of Participants With Lymphoproliferative Disease (PTLD) at 1 Year Post-Transplant	1 year Post-Transplant	The cumulative incidence of lymphoproliferative disease at 1-year post-transplant is described with 95% confidence intervals for each treatment group using the Aalen-Johansen estimator, treating death as a competing event.
Percentage of Participants With Chronic GVHD Post-transplant	6, 12 months post-transplant	Percentage of participants with chronic GVHD (cGVHD) at one-year will be estimated with 95% confidence intervals for each treatment group using the cumulative incidence estimate with the complementary log-log transformation, treating death prior to cGVHD as a competing event. Chronic GVHD is based on NIH Consensus Criteria (2014 NIH Consensus Criteria) and includes mild, moderate and severe chronic GVHD. Eight organs were scored on a 0-3 scale to reflect degree of cGVHD involvement. Liver and pulmonary function test results and use of systemic therapy for treatment of cGVHD were also recorded. Assessment of cGVHD occurred up to one-year post-transplant. This endpoint considers any cGVHD onset. A multivariate Cox regression model for the cause-specific hazard of cGVHD was used to compare the treatment groups, after adjustment for baseline characteristics as described for the primary endpoint.
Number of Participants With Immunosuppression-Free Survival (ISFS) at 1 Year Post-transplant	1 year post-transplant	Participants who are alive, relapse-free, and do not need ongoing immune suppression (IS) to control GVHD at one year post-transplant are considered successes for the endpoint immunosuppression-free survival (ISFS). Immune suppression is defined as any systemic agents used to control or suppress GVHD. Corticosteroid doses greater than 10 mg were considered active systemic immune suppression treatment. Participants who discontinued immune suppression within 15 days or less prior to the 1-year time point was considered to be on immune suppression for this endpoint.
Percentage of Participants With Neutrophil Recovery Post-transplant	Days 28 and day 100 post-transplant	Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) greater than or equal to 500/mm\^3 for three consecutive measurements on three different days. The first of the three days will be designated the day of neutrophil recovery. The competing event is death without neutrophil recovery. For participants who never drop ANC below 500/mm\^3, the date of neutrophil recovery will be Day +1 post-transplant. The cumulative incidence of neutrophil recovery by Day 28 and Day 100 was described for each treatment group with point estimates and 95% confidence intervals using the complementary log-log transformation and treating death as a competing event.
Summary Statistics for Donor Chimerism	Day 28 and Day 100 post-transplant	Donor cell engraftment were assessed with donor/recipient chimerism studies. Mixed chimerism is defined as the presence of donor cells, as a percentage of total cells to be less than 95% but at least 5% in the bone marrow or peripheral blood. Full donor chimerism is defined as greater than or equal to 95% of donor cells. Mixed and full chimerism will be evidence of donor cell engraftment. Donor cells of less than 5% will be considered as graft rejection. Donor chimerism at Day 28 and Day 100 after transplant in each of the randomized treatment arms will be described numerically as median and range for those evaluable.
Number of Participants With Grade 2 and 3 Infections	1 year post-transplant	All Grade 2 and 3 infections were reported according to the BMT CTN Technical Manual of Procedures (MOP) up to 1 year post-transplant. The frequency of Grade 2-3 infections and the number of participants experiencing infections occurring within 1 year post-transplant, are tabulated by treatment arm, organism, time period of infection onset, and severity, with Grade defined per the BMT CTN Technical MOP.
Percentage of Participants With CMV at Day 100 Post-transplant	Day 100 post-transplant	The cumulative incidence of initiation of systemic treatment for CMV was compared between the treatment groups using the Gray's test, with death treated as a competing risk. Estimates of the cumulative incidence of CMV reactivation are provided at Day 100 post-transplant.
Percentage of Participants With Disease-Free Survival (DFS) at 1 Year Post-transplant	1 year post-transplant	DFS is defined as being alive and free of relapse/progression of the primary disease. The time from transplant until death or relapse/progression (DFS failure) was described for each treatment arm using the Kaplan-Meier estimator, with numbers of subjects at risk at specific time points presented for each treatment group. A multivariate Cox regression model for the hazard of death will be used to compare the treatment groups, after adjustment for baseline characteristics as described for the primary endpoint.
Percentage of Participants With Immunosuppression-Free Survival (ISFS) at 1 Year Post-transplant	1 year post-transplant	Participants who are alive, relapse-free, and do not need ongoing immune suppression to control GVHD at one year post-transplant are considered successes for the endpoint immunosuppression-free survival (ISFS). Percentage of participants alive, relapse free, and off immune suppression at 1 year post-transplant were described for each treatment group, along with 95% Clopper-Pearson confidence intervals.
Number of Participants With Each Level of Donor Cell Engraftment Post-transplant	Day 28 and Day 100 post-transplant	Donor cell engraftment were assessed with donor/recipient chimerism studies. Mixed chimerism is defined as the presence of donor cells, as a proportion of total cells to be less than 95% but at least 5% in the bone marrow or peripheral blood. Full donor chimerism is defined as greater than or equal to 95% of donor cells. Mixed and full chimerism will be evidence of donor cell engraftment. Donor cells of less than 5% will be considered as graft rejection. The number of participants with each level of chimerism described above is described as part of this outcome.
Percentage of Participants With Overall Survival (OS) at 1 Year Post-transplant	1 year post-transplant	The event for this endpoint OS is death from any cause post-transplant. Time to overall survival is defined as the time interval between date of transplant and date of death from any cause. Surviving participants will be censored at last follow-up or 1 year post-transplant, whichever comes first. The time from transplant until death from any cause was described graphically for each treatment arm using the Kaplan-Meier estimator, with numbers of subjects at risk at specific time points presented for each treatment group. A multivariate Cox regression model for the hazard of death will be used to compare the treatment groups, after adjustment for baseline characteristics as described for the primary endpoint.
Percentage of Participants With Treatment-related Mortality (TRM) Post-transplant	Days 100, 180 and 1 year post-transplant	An event for this endpoint TRM is death without evidence of disease progression or recurrence. Disease progression or recurrence will be considered a competing event. The time from transplant until TRM, or cumulative incidence, estimated at specific time points along with 95% CIs computed using the complementary log-log transformation, treating relapse/progression of the primary disease as a competing risk. A multivariate Cox regression model for the cause-specific hazard of TRM was used to compare the treatment groups, after adjustment for baseline characteristics as described for the primary endpoint.
Percentage of Participants With Grade 2 and 3 Infections	6 months and 1 year post-transplant	Grade 2 and 3 infections, as defined by the BMT CTN Technical Manual of Procedures (MOP), are reported on the study. The cumulative incidence of infections post transplantation, treating death as a competing risk, were compared between the treatment groups using the Gray's test.

Trial Locations

Locations (39): Johns Hopkins University
🇺🇸
Baltimore, Maryland, United States
Dana Farber Cancer Institute/Brigham & Women's
🇺🇸
Boston, Massachusetts, United States
Ohio State/Arthur G. James Cancer Hospital
🇺🇸
Columbus, Ohio, United States
Baylor College of Medicine/The Methodist Hospital
🇺🇸
Houston, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸
Seattle, Washington, United States
City of Hope National Medical Center
🇺🇸
Duarte, California, United States
University of Kansas Hospital
🇺🇸
Kansas City, Kansas, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
University of California, San Francisco
🇺🇸
San Francisco, California, United States
University of Miami
🇺🇸
Miami, Florida, United States
Indiana University Simon Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Indiana BMT - St. Francis Hospital
🇺🇸
Indianapolis, Indiana, United States
Karmanos Cancer Institute, Children's Hospital of Michigan
🇺🇸
Detroit, Michigan, United States
Mayo Clinic - Rochester
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Rochester, Minnesota, United States
Duke University Medical Center
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Durham, North Carolina, United States
Oregon Health & Science University
🇺🇸
Portland, Oregon, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Stanford Hospital and Clinics
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Stanford, California, United States
University of Florida College of Medicine (Shands)
🇺🇸
Gainesville, Florida, United States
Emory University
🇺🇸
Atlanta, Georgia, United States
Blood & Marrow Transplant Program at Northside Hospital
🇺🇸
Atlanta, Georgia, United States
H. Lee Moffitt Cancer Center
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Tampa, Florida, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
Loyola University
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Maywood, Illinois, United States
University of Iowa Hospitals and Clinics
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Iowa City, Iowa, United States
Dana Farber Cancer Institute/Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Washington University/Barnes Jewish Hospital
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Saint Louis, Missouri, United States
Mount Sinai Medical Center
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New York, New York, United States
University Hospitals of Cleveland/Case Western
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Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
University of Pennsylvania Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
University of Texas, MD Anderson Cancer Research Center
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Houston, Texas, United States
University of Wisconsin Hospital & Clinics
🇺🇸
Madison, Wisconsin, United States
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
University of North Carolina
🇺🇸
Chapel Hill, North Carolina, United States
Virginia Commonwealth University, MCV Hospital
🇺🇸
Richmond, Virginia, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States