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This research is a phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational intervention to learn whether it works in treating a specific cancer. "Investigational" means that the study intervention is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not yet approved this study intervention for your type of cancer.
All participants on this study are treated in an identical manner. The investigators are doing this study because there continues to be a significant risk of relapse of disease after reduced intensity transplantation. In studies which have compared transplants using high-doses of chemotherapy and/or radiation versus reduced intensity transplants, patients undergoing reduced intensity transplants appear to have higher rates of relapse, but lower rates of toxicity and complication. This study attempts to utilize clofarabine, a newer chemotherapy agent shown to be quite active in AML, ALL, and MDS, to increase the anti-tumor effects of the conditioning regimen without accumulating unacceptable toxicity.
The reduced intensity allogeneic stem cell transplantation procedure involves giving you chemotherapy in relatively less intense doses to suppress your immune system. This is followed by an infusion of healthy blood stem cells from a matched related donor or a matched unrelated volunteer donor. It is hoped that these donor cells can eventually then attack any cancer cells which remain.
In this research study, the investigators are looking to see how well this new combination of busulfan and clofarabine works in reduced intensity allogeneic stem cell transplantation. By "works" the investigators mean to analyze safety, ability of donor cells to engraft (take hold), as well as measures of complications including toxicity, infections, graft-vs-host disease (GVHD), and relapse.
You will start the conditioning regimen, which is also called the preparative regimen. Conditioning is done to kill more cancer cells which may remain as well as prepare your body for transplant. You will receive the conditioning drugs into a vein. The conditioning regimen consists of the following drugs: Busulfan and Clofarabine.
While you are in the hospital you will have regular physical exams and you will be asked specific questions about any problems that you might be having. You will also have blood tests every day to look at how your bone marrow is recovering, to give possible transfusional support, and how to see how your liver and kidneys are functioning.
You will receive the following drugs before and after the allogeneic stem cell transplant: Neupogen (G-CSF) injections, drugs to prevent infections, Tacrolimus to prevent GVHD and Methotrexate.
You will have routine and regular follow-up in the transplant clinic after discharge from the hospital. The following will be performed at each visit:
Physical exam to monitor your health and check for signs of GVHD, infections and any side effects you may be having; Blood draw for routine blood tests to measure your blood cell count and chemistry; Blood tests to see if the transplanted stem cells are being accepted and are growing in the body (engraftment); Bone marrow biopsy to see the status of the underlying disease (to be done around 100 days after the stem cell transplant).
You will be asked to return to the clinic, at a minimum, for follow-up visits at 6 months, 9 months, 12 months, 18 months and 24 months after your stem cell transplant.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BuClo RIC + SCT | Experimental | Busulfan and Clofarabine (BuClo) reduced intensity conditioning (RIC) followed by allogeneic stem cell Transplantation (SCT) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Busulfan | Drug | Busulfan as part of reduced intensity conditioning prior to allogeneic stem cell transplantation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Assessment of Donor Stem Cell Engraftment: ANC Count | Patients are considered to have achieved donor cell engraftment if they have an absolute neutrophil count (ANC) of at least 500 cells/uL of blood for 3 consecutive measurements and at least 75% of hematopoietic elements are donor-derived as determined by chimerism assays from peripheral blood prior to day +40 after Busulfan/Clofarabine (BuClo) reduced intensity allogeneic stem cell transplantation | 1, 2, 3, and 4 weeks after transplantation |
| Donor Stem Cell Engraftment: Platelet Count | Platelet recovery was defined as having a platelet count of at least 20,000 platelets/uL of blood on 2 consecutive measurements without transfusional support prior to day +100 after BuClo RIC HSCT. | 1, 2, 3, 4, 8, and 14 weeks post transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Cumulative Incidence of Non-relapse Mortality | The percentage of participants that experienced non-relapse mortality (NRM) at day 100 and 1 year after BuClo RIC SCT. Non-relapse mortality is any mortality that is not associated with or proceeded by disease progression of prior cancers. | 100 days, 1 year |
| Progression-Free and Overall Survival |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yi-Bin Chen, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States | ||
| Brigham and Women's Hospital |
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| ID | Title | Description |
|---|---|---|
| FG000 | BuClo RIC + SCT | BuClo RIC SCT Busulfan: Busulfan as part of reduced intensity conditioning prior to allogeneic stem cell transplantation Clofarabine: Clofarabine as part of reduced intensity conditioning prior to allogeneic stem cell transplantation Allogeneic Stem Cell Infusion: Allogeneic stem cell transplantation after reduced intensity conditioning with busulfan / clofarabine chemotherapy |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | BuClo RIC + SCT | BuClo RIC SCT Busulfan: Busulfan as part of reduced intensity conditioning prior to allogeneic stem cell transplantation Clofarabine: Clofarabine as part of reduced intensity conditioning prior to allogeneic stem cell transplantation Allogeneic Stem Cell Infusion: Allogeneic stem cell transplantation after reduced intensity conditioning with busulfan / clofarabine chemotherapy |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Assessment of Donor Stem Cell Engraftment: ANC Count | Patients are considered to have achieved donor cell engraftment if they have an absolute neutrophil count (ANC) of at least 500 cells/uL of blood for 3 consecutive measurements and at least 75% of hematopoietic elements are donor-derived as determined by chimerism assays from peripheral blood prior to day +40 after Busulfan/Clofarabine (BuClo) reduced intensity allogeneic stem cell transplantation | One participant experienced early death before engraftment. Outcome measure was assessed among the remaining 33 evaluable participants. | Posted | Count of Participants | Participants | 1, 2, 3, and 4 weeks after transplantation |
|
Duration of the study, median duration of 20 months
Adverse events were assessed from the start of reduced intensity conditioning with Busulfan/Clofarabine until the participant died, relapsed/ had progressive disease, was taken off the study, or withdrew consent (median duration of 20 months). Adverse events were assessed at every study visit. Adverse events were assessed with the use of physicals/review of systems and routine laboratory tests.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment Arm | Reduced Intensity Conditioning with Busulfan/Clofarabine followed by Allogeneic Stem Cell Transplantation (BuClo RIC SCT) Busulfan: Busulfan as part of reduced intensity conditioning prior to allogeneic stem cell transplantation Clofarabine: Clofarabine as part of reduced intensity conditioning prior to allogeneic stem cell transplantation Allogeneic Stem Cell Infusion: Allogeneic stem cell transplantation after reduced intensity conditioning with busulfan / clofarabine chemotherapy |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Kidney Injury | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Yi-Bin Chen, MD | Massachusetts General Hospital | 617-726-0187 | YCHEN6@PARTNERS.ORG |
Not provided
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D002066 | Busulfan |
| D000077866 | Clofarabine |
| ID | Term |
|---|---|
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| Clofarabine | Drug | Clofarabine as part of reduced intensity conditioning prior to allogeneic stem cell transplantation |
|
| Allogeneic Stem Cell Infusion | Procedure | Allogeneic stem cell transplantation after reduced intensity conditioning with busulfan / clofarabine chemotherapy |
|
The 1-year and 2-year progression-free and overall survival measured from the time of stem cell transplantation. Progression is the recurrence or increase in the number of cancer cells found in the body. |
| 1 year, 2 years |
| Cumulative Incidence and Severity of Acute GVHD Within 100 Days Post Transplant | The percentage of participants who experienced grades 2-4 and grades 3-4 acute graft-versus-host disease (GVHD) by 100 days post transplantation. GVHD is a condition that can occur following an allogenic stem cell transplantation when the donated bone marrow or peripheral stem cells view the recipients body as foreign and the donated cell/marrow attack the body. Acute GVHD is generally observed within the first 100 days post transplant. Acute GVHD is associated with increased treatment related morbidity and mortality. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening. The grade of the GVHD is determined by grading GHVD associated adverse events. Associated adverse events were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4 which uses the same mild, moderate, severe, life threatening grading system as the overall GHVD assessment. | 100 days |
| Cumulative Incidence of Chronic GVHD at One Year | The percentage of participants who experienced chronic Graft Versus Host Disease (GVHD) by one year. GVHD is a condition that can occur following an allogenic stem cell transplantation when the donated bone marrow or peripheral stem cells view the recipients body as foreign and the donated cell/marrow attack the body. Chronic GVHD normally occurs after the first 100 days post transplantation. Chronic GVHD can adversely influence long term survival. | 1 year |
| Incidence of Hepatic Veno-occlusive Disease | The number of participants that experienced hepatic veno-occlusive disease (VOD). VOD is a condition in which some of the small veins in the liver are obstructed. | 2 years |
| Grade 3 or 4 Toxicities | The number of participants that experienced the specified grade 3 and 4 non-hematological toxicities during treatment and follow-up as assessed by Common Terminology Criteria for Adverse Events version 4(CTAE v 4.0). Grade 3 toxicity is considered to be severe and grade 4 is considered to be life threatening. | 2 years |
| Infection-related Complications | The number of patients with infection-related complications | 2 years |
| Boston |
| Massachusetts |
| 02115 |
| United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Diagnosis | Count of Participants | Participants |
|
| Hematopoietic Cell Transplantation (HCT) Refined Disease Risk Index (DRI) | Categorization of disease risk determined by the Refined Disease Risk Index (DRI) for patients receiving Hematopoietic Cell Transplantation (HCT). | Count of Participants | Participants |
|
| Disease Stage | Disease stage at time of treatment:
| Count of Participants | Participants |
|
| Cytogenics for patients with AML/MDS | Southwest Oncology Group Risk Stratification | The 30 participants diagnosed with ALL or MDS | Count of Participants | Participants |
|
| ALL Cytogenics | The four participants diagnosed with ALL | Count of Participants | Participants |
|
| Hematopoietic cell transplantation specific comorbidity index (HCT-CI) | The HTC-CI provides information about the overall and non-relapse mortality risk a patient is likely to experience following a hematopoietic cell transplantation. Lower scores represent lower risk and higher scores represent higher risk. The score is produced by adding up the number of specific risk factors a patient has and can range from 0 to 26. The index is usually characterized as risk categories from 0 to 4+ with patients with four or more risk factors considered high risk. | Median | Full Range | units on a scale |
|
| Donor Type | Matched = Human Leukocyte Antigen (HLA) matched; Related = donor and recipient are genetic relatives | Count of Participants | Participants |
|
| Cytomegalovirus Serostatus | Count of Participants | Participants |
|
|
|
| Primary | Donor Stem Cell Engraftment: Platelet Count | Platelet recovery was defined as having a platelet count of at least 20,000 platelets/uL of blood on 2 consecutive measurements without transfusional support prior to day +100 after BuClo RIC HSCT. | One participant experienced early death before engraftment. Outcome measure was assessed among the remaining 33 evaluable participants. | Posted | Count of Participants | Participants | 1, 2, 3, 4, 8, and 14 weeks post transplant |
|
|
|
| Secondary | Cumulative Incidence of Non-relapse Mortality | The percentage of participants that experienced non-relapse mortality (NRM) at day 100 and 1 year after BuClo RIC SCT. Non-relapse mortality is any mortality that is not associated with or proceeded by disease progression of prior cancers. | Posted | Number | 95% Confidence Interval | percentage of participants who died | 100 days, 1 year |
|
|
|
| Secondary | Progression-Free and Overall Survival | The 1-year and 2-year progression-free and overall survival measured from the time of stem cell transplantation. Progression is the recurrence or increase in the number of cancer cells found in the body. | Posted | Number | 95% Confidence Interval | percentage of participants | 1 year, 2 years |
|
|
|
| Secondary | Cumulative Incidence and Severity of Acute GVHD Within 100 Days Post Transplant | The percentage of participants who experienced grades 2-4 and grades 3-4 acute graft-versus-host disease (GVHD) by 100 days post transplantation. GVHD is a condition that can occur following an allogenic stem cell transplantation when the donated bone marrow or peripheral stem cells view the recipients body as foreign and the donated cell/marrow attack the body. Acute GVHD is generally observed within the first 100 days post transplant. Acute GVHD is associated with increased treatment related morbidity and mortality. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening. The grade of the GVHD is determined by grading GHVD associated adverse events. Associated adverse events were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4 which uses the same mild, moderate, severe, life threatening grading system as the overall GHVD assessment. | Posted | Number | 95% Confidence Interval | percentage of Participants | 100 days |
|
|
|
| Secondary | Cumulative Incidence of Chronic GVHD at One Year | The percentage of participants who experienced chronic Graft Versus Host Disease (GVHD) by one year. GVHD is a condition that can occur following an allogenic stem cell transplantation when the donated bone marrow or peripheral stem cells view the recipients body as foreign and the donated cell/marrow attack the body. Chronic GVHD normally occurs after the first 100 days post transplantation. Chronic GVHD can adversely influence long term survival. | Posted | Number | 95% Confidence Interval | percentage of participants | 1 year |
|
|
|
| Secondary | Incidence of Hepatic Veno-occlusive Disease | The number of participants that experienced hepatic veno-occlusive disease (VOD). VOD is a condition in which some of the small veins in the liver are obstructed. | Posted | Count of Participants | Participants | 2 years |
|
|
|
| Secondary | Grade 3 or 4 Toxicities | The number of participants that experienced the specified grade 3 and 4 non-hematological toxicities during treatment and follow-up as assessed by Common Terminology Criteria for Adverse Events version 4(CTAE v 4.0). Grade 3 toxicity is considered to be severe and grade 4 is considered to be life threatening. | Posted | Count of Participants | Participants | 2 years |
|
|
|
| Secondary | Infection-related Complications | The number of patients with infection-related complications | Posted | Count of Participants | Participants | 2 years |
|
|
|
| 15 |
| 34 |
| 14 |
| 34 |
| 24 |
| 34 |
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Erythroderma | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertriglyceridemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Lung Infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Neutrophil Count Decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Viral Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Anal mucositis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Depression | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Erythroderma | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Glucose intolerance | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hemoglobin increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Hip fracture | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Lung infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Mucositis oral | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Muscle weakness lower limb | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Renal and urinary disorders - Other, specify | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Skin infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Thromboembolic event | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Weight loss | Investigations | CTCAE (4.0) | Systematic Assessment |
|
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| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D001855 | Bone Marrow Diseases |
| D008698 |
| Mesylates |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D000227 | Adenine Nucleotides |
| D011685 | Purine Nucleotides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D009711 | Nucleotides |
| D012265 | Ribonucleotides |
|
| Overall Survival at 2 years |
|
| Title | Measurements |
|---|---|
|
| Mucositis |
|
| Increased bilirubin |
|
| Increased alanine aminotransferase |
|
| Increased aspartate aminotransferase |
|
| Engraftment Syndrome |
|
| Febrile Neutropenia |
|
| Sepsis |
|
| Acute Renal Failure |
|
| Diffuse alveolar hemorrhage |
|
| Idiopathic pneumonia syndrome |
|