Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Fludarabine

Fludarabine phosphate

Melphalan

Busulfan

Vidarabine

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antiviral Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

fludarabine (30 mg/m\^2/day, days -6 to days -2, the total dase is 150 mg/m\^2) and busulfan (3.2 mg/kg/day, days -3 to days -2, the total dose is 6.4 mg/kg)

fludarabine (30 mg/m\^2/day, days -6 to days -2, the total dose is 150 mg/m\^2) and melphalan (70 mg/m\^2/day, days -3 to days -2, the total dose is 140 mg/m\^2)

Fludarabine with total dose of 150 mg/m\^2 in combination with Busulfan with total dose of 6.4 mg/kg

Fludarabine and Busulfan

Fludarabine with total dose of 150 mg/m\^2 in combination with Melphalan with total dose of 140 mg/m\^2

Fludarabine and Melphalan

Linghui Xia, Professor

Wei Shi, Professor

Miaomiao Zhao, Doctor

The goal of this clinical trial is to compare outcomes of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan) in allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) patients. The main questions it aims to answer are:

* The safety of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan) in allogeneic hematopoietic stem cell transplantation for adult AML/MDS patients with HCT-CI≥3 or aged ≥55 years.
* The efficacy of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan) in allogeneic hematopoietic stem cell transplantation for adult AML/MDS patients with HCT-CI≥3 or aged ≥55 years.

Participants will be randomized to one of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan)

Patients are randomized to one of two reduced intensity conditioning (RIC) regimens: the combination of fludarabine (30 mg/m\^2/day, days -6 to days -2, the total dase is 150 mg/m\^2) and busulfan (3.2 mg/kg/day, days -3 to days -2, the total dose is 6.4 mg/kg) (Flu/Bu) or fludarabine (30 mg/m\^2/day, days -6 to days -2, the total dose is 150 mg/m\^2) and melphalan (70 mg/m\^2/day, days -3 to days -2, the total dose is 140 mg/m\^2) (Flu/Mel). A total of 200 patients (100 to each arm) will be recruited in this study over a period of two years. Patients will be followed for up to 18 months from allogeneic hematopoietic stem cell transplantation.

Participants will be randomized to one of two reduced intensity conditioning (RIC) regimens (fludarabine plus busulfan and fludarabine plus melphalan)

Reduced Intensity Conditioning Regimens for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Reduced Intensity Conditioning With Fludarabine and Busulfan Versus Fludarabine and Melphalan Before Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Randomised, Single-Center, Phase III Study

Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500x10\^6/liter for 3 continuous measurements on different days. The first of the 3 days will be labeled as the day of neutrophil engraftment. Platelet engraftment is defined as achieving platelet counts greater than 20,000/microliter for continuous measurements over 7 days without requiring platelet transfusions. The first day of the 7 days will be marked as the day of platelet engraftment.

List the type, number, and severity of infection events

The severity of oral ulcer or diarrhea in the early stage after transplantation, clinically significant abnormal laboratory findings.

Number of Lymphocyte Subsets of Participants

Survival without relapse or progression of the primary disease. Kaplan-Meier (KM) method was used to estimate median PFS.

Overall survival is defined as survival duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS

Death not due to recurrence or progression of the primary disease. Recurrence was considered as a competing risk event, and the Gray test was used for statistical analysis.

Relapse of the primary disease. Non-relapse mortality (TRM) was considered as a competing risk event, and Gray's test was used for statistical analysis.

Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:

Skin stage:

0: No rash

Rash \<25% of body surface area Rash on 25-50% of body surface area Rash on \> 50% of body surface area Generalized erythroderma with bullous formation

Liver stage (based on bilirubin level)\*:

0: \<2 mg/dL

2-3 mg/dL 3.01-6 mg/dL 6.01-15.0 mg/dL \>15 mg/dL

GI stage\*:

0: No diarrhea or diarrhea \<500 mL/day

Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD Diarrhea 1000-1499 mL/day Diarrhea \>1500 mL/day Severe abdominal pain with or without ileus \* If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.

GVHD grade:

0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4

Chronic GVHD is classified as the occurrence of mild, moderate, or severe chronic GVHD per 2005 NIH Consensus Criteria (Filipovich et al. 2005)

Wuhan Union Hospital, China

Immune System Diseases

Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Lymphoma

Acquired Immunodeficiency Syndrome

HIV Infections

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Antirheumatic Agents

Cyclophosphamide

One regimen from either reduced-intensity conditioning (RIC) (Fludarabine and Busulfan; or Fludarabine and Melphalan) or myeloablative conditioning (MAC) (Busulfan and Fludarabine; or Cyclophosphamide and Total Body Irradiation) will be administered prior to allogeneic hematopoietic cell transplantation (HCT).

RIC Regimen (Flu/Bu): Fludarabine total dose: 120-180 mg/m\^2, Busulfan: ≤ 8 mg/kg PO or 6.4 mg/kg IV). Recommended regimen:

* Days -6 to -2: Flu (30 mg/m\^2/day, total dose of 150 mg/m\^2)
* Days -5 to -4: Busulfan (4mg/kg/day PO or 3.2 mg/kg IV, 130 mg/m\^2/day, total dose of 8 mg/kg PO or 6.4 mg/kg IV, or 260 mg/m\^2 IV, respectively)

Patients with a creatinine clearance of 40-70 ml/min (measured or calculated) should have a 20 percent dose reduction in Fludarabine dosage.

Busulfan will be dosed according to the recipient's ideal body weight (IBW), unless the patient weighs more than 125 percent of IBW, in which case the drug will be dosed according to the adjusted IBW.

RIC Regimen (Flu/Mel): Fludarabine total dose: 120-180 mg/m\^2, Melphalan total dose: less than or equal to 150 mg/m\^2. Recommended regimen:

* Days -5 to -2: Flu (30mg/m\^2/day, total dose of 120 mg/m\^2)
* Day -1: Mel (140mg/m\^2)

Patients with a creatinine clearance of 40-70 ml/min (measured or calculated) should have a 20 percent dose reduction in Fludarabine dosage.

MAC Regimen (Bu/Flu): Fludarabine total dose: 120-180mg/m\^2 Busulfan total dose less than or equal to 16mg/kg PO or 12.8 mg/kg IV. Recommended regimen:

* Days -5 to -2: Busulfan (4 mg/kg/day PO with Bu Css 900 plus/equal to 100 ng/mL (or per institutional standard), 3.2 mg/kg/day IV or 130 mg/m\^2/day IV; total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively)
* Days -5 to -2: Flu (30 mg/m\^2/day, total dose of 120 mg/m\^2)

Patients with a creatinine clearance of 40-70 ml/min (measured or calculated) should have a 20 percent dose reduction in Fludarabine dosage.

Busulfan will be dosed according to the recipient's ideal body weight (IBW), unless the patient weighs more than 125 percent of IBW, in which case the drug will be dosed according to the adjusted IBW.

Busulfan and Fludarabine

MAC Regimen (Cy/TBI): Cyclophosphamide total dose: 120 mg/kg, Fractionated TBI total dose: 1200-1420 cGy Recommended regimen:

* Days -7 to -4: TBI (total dose of 1200-1420 cGy)
* Days -3 to -2: Cy (60 mg/kg/day, total dose of 120 mg/kg)

Cyclophosphamide will be dosed according to the recipient's ideal body weight (IBW), unless the patient weighs less than IBW, in which case the drug will be dosed according to the actual body weight.

Cyclophosphamide and Total Body Irradiation

Mary Horowitz, MD

The rationale for this trial is to demonstrate the feasibility and safety of allogeneic HCT for patients with chemotherapy-sensitive hematological malignancies and coincident HIV-infection. In particular, the trial will focus on the 100-day non-relapse mortality as an indicator of the safety of transplant in this patient population. Correlative assays will focus upon the incidence of infectious complications in this patient population, the evolution of HIV infection and immunological reconstitution. Where feasible (and when this can be accomplished without compromise of either the donor quality or the timeliness of transplantation), an attempt will be made to identify donors who are homozygotes for the delta32 mutation for CCR5.

The study is designed to evaluate the feasibility and safety of reduced-intensity and fully-ablative allogeneic hematopoietic cell transplantation (HCT) for patients with hematological malignancies or myelodysplastic syndromes (MDS) who have HIV infection. The goal of the study is to assess the 100 day Non-relapse Mortality as well as immunological reconstitution in this patient population. Where feasible, an attempt will be made to identify human leukocyte antigen (HLA)-compatible hematopoietic stem cell donors who are homozygotes for the delta32 mutation of the chemokine receptor 5 (CCR5delta32). Patients will undergo a treatment plan review prior to registration on the trial. All patients will undergo allogeneic HCT from a matched sibling or unrelated donor.

Allogeneic Transplant in HIV Patients (BMT CTN 0903)

Allogeneic Hematopoietic Cell Transplant for Hematological Cancers and Myelodysplastic Syndromes in HIV-Infected Individuals (BMT CTN #0903)

Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).

The events for non-relapse mortality are death due to any cause other than relapse of the underlying malignancy.

Overall survival is defined as the time from transplant to death from any cause.

Relapse/Progression is defined as relapse or progression of the primary malignancy.

Patients will be assessed for disease status at Day 100 post-HCT, classified as complete remission, partial remission, stable disease, and relapse/progressive disease.

Recovery of hematologic function is described by the time to neutrophil and platelet recovery. Time to neutrophil recovery will be the first of three consecutive days of \> 500 neutrophils/μL following the expected nadir. Time to platelet engraftment will be described by the date when platelet count is \> 20,000/μL for the first of three consecutive labs with no platelet transfusions 7 days prior.

Donor T-cell and myeloid chimerism will be described separately by conditioning regimen intensity (myeloablative or reduced intensity) according to proportions with mixed chimerism (5-95% donor cells out of all), full chimerism (\>95% donor cells), or graft rejection (\<5% donor cells).

Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:

Skin stage:

0: No rash

1. Rash \<25% of body surface area
2. Rash on 25-50% of body surface area
3. Rash on \> 50% of body surface area
4. Generalized erythroderma with bullous formation

Liver stage (based on bilirubin level)\*:

0: \<2 mg/dL 1.2-3 mg/dL 2.3.01-6 mg/dL 3.6.01-15.0 mg/dL 4.\>15 mg/dL

GI stage\*:

0: No diarrhea or diarrhea \<500 mL/day

1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
2. Diarrhea 1000-1499 mL/day
3. Diarrhea \>1500 mL/day
4. Severe abdominal pain with or without ileus \* If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.

GVHD grade:

0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4

Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.

The maximum grade of infections reported by participants are described, as defined in the BMT CTN Technical MOP.

National Heart, Lung, and Blood Institute (NHLBI)

National Cancer Institute (NCI)

Blood and Marrow Transplant Clinical Trials Network

National Marrow Donor Program

Medical College of Wisconsin

Allogeneic Transplant

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Assesses patient self-perceived global quality of life and functioning, where 100 equals perfect quality of life.

Karnofsky Performance Score

Primary Malignancy

Leukemia Stage

Participants with lymphoma (Hodgkin's or non-Hodgkin's)

Lymphoma Stage

HIV Viral Load

Recipient Cytomegalovirus Status

Number of Regimens of Induction Chemotherapy

Number of Regimens of Salvage Chemotherapy

Donor/recipient matching described by relatedness and HLA matching. A matched donor corresponds to matching on 8/8 HLA loci, while mismatched donor indicates 7/8 matching.

Donor Type

CD4 T-cell Count

Adam Mendizabal, PhD

Day 100

1 Year

2 Years

Percentage of Participants With Non-Relapse Mortality

6 Months

Percentage of Participants With Overall Survival

Percentage of Participants With Relapse/Progression

Primary Cause of Death

Disease Status

Day 28 Neutrophil Recovery

Day 100 Platelet Recovery

Percentage of Participants Recovering Hematologic Function

Week 4

Myeloablative conditioning (MAC) (Busulfan and Fludarabine or Cyclophosphamide and Total Body Irradiation) will be administered prior to allogeneic hematopoietic cell transplantation (HCT).

Myeloablative Allogeneic Transplant

Reduced-intensity conditioning (RIC) (Fludarabine and Busulfan; or Fludarabine and Melphalan) will be administered prior to allogeneic hematopoietic cell transplantation (HCT).

Reduced Intensity Allogeneic Transplant

Chimerism

Grade II-IV Acute GVHD

Grade III-IV Acute GVHD

Percentage of Participants With Acute Graft-Versus-Host Disease (GVHD)

Percentage of Participants With Chronic Graft-Versus-Host Disease (GVHD)

Infection Severity

Overall Study

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

(Flu/Bu)

* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

(Flu/Mel)

* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2

(Bu/Flu)

* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)

(Bu/Cy)

* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Busulfan and Cyclophosphamide

(Cy/TBI)

* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

The study is designed as a Phase III, multicenter trial comparing outcomes after allogeneic hematopoietic stem cell transplantation (HCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) between patients receiving myeloablative conditioning (MAC) versus reduced intensity conditioning (RIC) regimens.

Patients randomized to RIC will receive one of two regimen types: the combination of fludarabine (120-180 mg/m\^2) and busulfan (less than or equal to 8 mg/kg or IV equivalent) (Flu/Bu) or fludarabine (120-180 mg/m\^2) and melphalan (less than 150 mg/m\^2) (Flu/Mel). Patient randomized to MAC will receive one of three regimens: busulfan (16 mg/kg oral or 12.8 mg/kg IV equivalent) and cyclophosphamide (120 mg/kg) (Bu/Cy); or, busulfan (16 mg/kg PO or 12.8 mg/kg IV) and fludarabine (120-180 mg/m\^2) (Bu/Flu); or, cyclophosphamide (120 mg/kg) and total body irradiation (greater than 1200-1420cGy) (CyTBI). A total of 356 patients (178 to each arm) will be accrued on this study over a period of four years. Patients will be followed for up to 18 months from transplantation.

Reduced Intensity Regimen vs Myeloablative Regimen for Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901)

A Randomized, Multi-Center, Phase III Study of Allogeneic Stem Cell Transplantation Comparing Regimen Intensity in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia (BMT CTN #0901)

Findings will be published in a manuscript

Overall survival is defined as survival of death from any cause.

Relapse-free survival is defined as survival without relapse of the primary disease.

Disease Relapse is defined as relapse of the primary disease.

Treatment-related mortality is defined as death without a previous relapse of the primary disease.

Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500x10\^6/liter for 3 consecutive measurements on different days. The first of the 3 days will be designated the day of neutrophil engraftment. Platelet engraftment is defined as achieving platelet counts greater than 20,000/microliter for consecutive measurements over 7 days without requiring platelet transfusions. The first of the 7 days will be designated the day of platelet engraftment. Subjects must not have had platelet transfusions during the preceding 7 days.

Donor cell engraftment will be assessed by donor-recipient chimerism assays. Full donor chimerism is defined as the presence of at least 95% donor cells as a proportion of the total population in the peripheral blood or bone marrow. Graft rejection is defined as the presence of no more than 5% donor cells as a proportion of the total population. Mixed chimerism is defined as the presence of between 5% and 95% donor cells. Mixed or full donor chimerism will be considered evidence of donor engraftment.

Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:

Skin stage:

0: No rash

1. Rash \<25% of body surface area
2. Rash on 25-50% of body surface area
3. Rash on \> 50% of body surface area
4. Generalized erythroderma with bullous formation

Liver stage (based on bilirubin level)\*:

0: \<2 mg/dL

1. 2-3 mg/dL
2. 3.01-6 mg/dL
3. 6.01-15.0 mg/dL
4. \>15 mg/dL

GI stage\*:

0: No diarrhea or diarrhea \<500 mL/day

1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
2. Diarrhea 1000-1499 mL/day
3. Diarrhea \>1500 mL/day
4. Severe abdominal pain with or without ileus \* If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.

GVHD grade:

0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4

Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe.

Primary graft failure is defined by lack of neutrophil engraftment.

Secondary graft failure is defined by initial neutrophil engraftment followed by subsequent decline in neutrophil counts to less than 500x10\^6/liter that is unresponsive to growth factor therapy.

The maximum grade of toxicities reported by participants over the study duration are tabulated. Per the CTCAE criteria, toxicities are graded on a scale of 0-5, with higher numbers indicating greater severity. The categories correspond as follows:

3 - severe; 4 - life-threatening; 5 - fatal

The number and types of infection events reported are tabulated.

The maximum severity of infections reported by participants are tabulated.

The number of infections and the number of patients experiencing infections will be tabulated by type of infection, severity, and time period after transplant. The cumulative incidence of severe, life-threatening, or fatal infections will be compared between the two treatment arms at 6, 12, and 18 months from transplant or until death.

Primary cause of death was adjudicated using previously described criteria (Copelan et al. 2007). When relapse occurred, it was considered the primary cause of death regardless of other events.

Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Busulfan and Fludarabine: (Bu/Flu)

* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)

Busulfan and Cyclophosphamide: (Bu/Cy)

* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Cyclophosphamide and Total Body Irradiation: (Cy/TBI)

* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Myeloablative Conditioning Regimen (MAC)

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Fludarabine and Busulfan: (Flu/Bu)

* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Fludarabine and Melphalan: (Flu/Mel)

* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2

Reduced Intensity Conditioning (RIC)

Total

Primary Disease

Participants with MDS are categorized per 2008 WHO classification (Vardiman et al. 2009). Major features of each class are given below:

Refractory Anemia (RA): Anemia without marrow blasts or sideroblasts; Refractory Anemia with Ringed Sideroblasts (RARS): \> 15% marrow sideroblasts; Refractory Cytopenias with Multilineage Dysplasia (RCMD): Dysplasia in \>10% marrow cells; Isolated del(5q) (Del-5q): Isolated del(5q) in marrow; Unclassified (MDS-U) Refractory Anemia with Excess Blasts-1 (RAEB-1): 5-9% marrow blasts; Refractory Anemia with Excess Blasts-2 (RAEB-2): 10-19% marrow blasts;

MDS WHO Classification

Participants with AML are categorized per 2008 WHO classification (Vardiman et al. 2009). Major features of each class are given below:

AML with recurrent genetic abnormalities: Presence of specific genetic abnormalities known to be prognostic; AML with multilineage dysplasia: \> 50% of cells in at least 2 myeloid lineages are dysplastic; AML and MDS, therapy related: development of myeloid neoplasms in response to therapy that is diagnosed as either AML or MDS; AML not otherwise specified: AML that does not satisfy criteria for other classes

AML WHO Classification

Disease Duration

Disease risk status is defined according to cytogenetic and molecular abnormalities identified prior to transplantation and classified as standard or high risk. Among AML participants, high-risk disease is defined as the presence of cytogenetic abnormalities at 3q, 9q, 11q, 20q, 21q, or 17p; the presence of del(5q)/-5, -7/del(7q), t(6;9), or t(9;22); and/or FLT-3 internal tandem duplication mutation. Among MDS participants, high-risk disease is defined as the presence of \> 10% blasts in bone marrow.

Disease Risk Status

The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) (Sorror et al., 2005) summarizes relevant comorbidities present in participants prior to allogeneic transplant. Each comorbidity reported at the time of transplant is given a score of 0, 1, 2, or 3 and the overall HCT-CI score is the sum of the comorbidity scores, ranging from 0 - 26.

HCT-CI

Flu/Bu4: busulfan (16 mg/kg oral or 12.8 mg/kg IV) and fludarabine (120-180 mg/m2); Bu/Cy: busulfan (16 mg/kg oral or 12.8 mg/kg IV) and cyclophosphamide (120 mg/kg) ; Cy/TBI: cyclophosphamide (120 mg/kg) and total body irradiation (1200-1420 cGy); Flu/Mel: fludarabine (120-180 mg/m2) and melphalan (≤ 150 mg/m2); Flu/Bu2: fludarabine (120-180 mg/m2) with busulfan (≤ 8 mg/kg oral or 6.4 mg/kg IV);

Flu/Bu4, Bu/Cy, and Cy/TBI are myeloablative conditioning regimens, while Flu/Mel and Flu/Bu2 are reduced intensity conditioning regimens.

Conditioning Regimen

Prophylaxis for Graft Versus Host Disease

GVHD Prophylaxis

ATG Use

Donor Source

The null hypothesis is that there is no difference in overall survival at 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. 18 month overall survival was compared between treatment arms using the difference in Kaplan-Meier estimators, which should be close to 0 under the null hypothesis.

Percentage of Participants With Overall Survival (OS)

The null hypothesis is that there is no difference in relapse-free survival at 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. 18 month relapse-free survival was compared between treatment arms using the difference in Kaplan-Meier estimators, which should be close to 0 under the null hypothesis.

Percentage of Participants With Relapse-Free Survival (RFS)

The null hypothesis is that there is no difference in the cumulative incidence of disease relapse during the first 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of disease relapse was compared between treatment arms using Gray's test, treating death as a competing risk.

Percentage of Participants With Disease Relapse

The null hypothesis is that there is no difference in the cumulative incidence of treatment-related mortality during the first 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of treatment-related mortality was compared between treatment arms using Gray's test, treating disease relapse as a competing risk.

Percentage of Participants With Treatment-related Mortality

The null hypothesis is that there is no difference in the cumulative incidence of neutrophil engraftment at Day 28 post-transplant between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of neutrophil engraftment at Day 28 was compared between treatment arms using the difference in Aalen-Johansen estimators, which should be close to 0 under the null hypothesis. Death was treated as a competing risk.

The null hypothesis is that there is no difference in the cumulative incidence of platelet engraftment at Day 60 post-transplant between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of platelet engraftment at Day 60 was compared between treatment arms using the difference in Aalen-Johansen estimators, which should be close to 0 under the null hypothesis. Death was treated as a competing risk.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Reduced Intensity Conditioning Regimens for Acute Myeloid Leukemia and Myelodysplastic Syndrome	NCT05674539	Acute Myeloid L... Myelodysplastic... Allogeneic Hema...	Fludarabine and... Fludarabine and...	18 Years -	Wuhan Union Hospital, China
Allogeneic Transplant in HIV Patients (BMT CTN 0903)	NCT01410344	Leukemia Lymphoma HIV	Fludarabine and... Fludarabine and... Busulfan and Fl... Cyclophosphamid...	15 Years -	Medical College of Wisconsin
Allogeneic Transplant in HIV Patients (BMT CTN 0903)	NCT01410344	Leukemia Lymphoma HIV	Fludarabine and... Fludarabine and... Busulfan and Fl... Cyclophosphamid...	15 Years -	Medical College of Wisconsin
Reduced Intensity Conditioning Regimens for Acute Myeloid Leukemia and Myelodysplastic Syndrome	NCT05674539	Acute Myeloid L... Myelodysplastic... Allogeneic Hema...	Fludarabine and... Fludarabine and...	18 Years -	Wuhan Union Hospital, China
Reduced Intensity Conditioning Regimens for Acute Myeloid Leukemia and Myelodysplastic Syndrome	NCT05674539	Acute Myeloid L... Myelodysplastic... Allogeneic Hema...	Fludarabine and... Fludarabine and...	18 Years -	Wuhan Union Hospital, China
Reduced Intensity Regimen vs Myeloablative Regimen for Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901)	NCT01339910	Leukemia, Myelo...	Fludarabine and... Fludarabine and... Busulfan and Fl... Busulfan and Cy... Cyclophosphamid...	18 Years - 65 Years	Medical College of Wisconsin

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