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| ID | Type | Description | Link |
|---|---|---|---|
| P30CA033572 | U.S. NIH Grant/Contract | View source | |
| CHNMC-IRB-94072 | Registry Identifier | NCI PDQ | |
| NCI-V94-0545 | |||
| CDR0000063845 | Registry Identifier | NCI PDQ |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of high-dose combination chemotherapy and peripheral stem cell transplantation in treating patients who have advanced or recurrent sarcoma.
OBJECTIVES: I. Determine the feasibility of sequential high-dose chemotherapy with ifosfamide and doxorubicin followed by melphalan and cisplatin, each followed by autologous peripheral blood stem cell support, in patients with high-risk or advanced sarcomas. II. Determine the toxic effects of this regimen in these patients. III. Determine response rate and disease-free and overall survival in these patients treated with this regimen.
OUTLINE: Beginning at least 4 weeks prior to the start of chemotherapy, patients receive filgrastim (G-CSF) subcutaneously daily until the completion of peripheral blood stem cell (PBSC) harvesting. Beginning 5 days after the start of G-CSF, PBSCs are collected over several days. Patients who do not mobilize sufficient cells undergo bone marrow harvest. Regimen A: Patients receive high-dose ifosfamide IV and doxorubicin IV continuously over 96 hours on days -8 to -4. 12.5% of PBSCs or bone marrow are reinfused on day -2 and 37.5% are reinfused on day 0. Patients receive G-CSF IV beginning on day 0 and continuing until blood counts recover. Regimen B: Beginning at least 4 weeks after day 1 of Regimen A, patients receive high-dose melphalan IV followed immediately by cisplatin IV on days -11 and -4. Patients receive G-CSF IV on days -10 to -6. 12.5% of PBSCs or bone marrow are reinfused on day -3 and the remaining 37.5% are reinfused on day 0. Patients receive G-CSF IV beginning on day 0 and continuing until blood counts recover. Patients are followed monthly for 1 year, every 3 months for 1 year, and then as needed for 3 years.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT | Experimental | Cycle 1 Day -8 through Day -4 (96h) Doxorubicin 150 mg/m2 (CI) + Ifosfamide 14 g/m2 mixed with mesna (CI) Day -3 Mesna 3.5 g/m2 over 24 h Day -2 12.5% of stem cell reinfused. Cycle2 Day -11 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -10 thru Day -6 G-CSF 5ug/kg Day -4 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -3 12.5% if stem cell reinfused Day 0 37.5% of stem cell reinfused |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| filgrastim | Biological | 5 ug/kg daily following stem cell reinfusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Grade 3 Bilirubin | Criteria for early termination of this feasibility study: > 2 patients experience grade 4 or 5 hematologic toxicity or more that 3 patients experience grade 3 hematologic toxicity; > 2 patients experience grade 3 hepatic or gastrointestinal toxicity or > 3 patients are unable to receive the second cycle of treatment; > 2 patients experience grade 5 toxicity related to treatment regimen. | 2 years after completion of treatment |
| Toxicities Counts | Number of patients with grade 3 and 4 toxicities observed during cycles 1 & 2 using the Common Toxicity Criteria Version for Chemotherapy. | 2 months after completion of second cycle of treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| 5-year Progression-free Survival | Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 25% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions. | Until disease progression, up to 5 Years |
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DISEASE CHARACTERISTICS: Histologically confirmed sarcomas in the following categories: Soft tissue sarcoma (STS) High-grade STS of the extremities Primary extending to fascia or locally recurrent At least 10 cm in greatest dimension or multifocal on surgical pathology Primary site controlled by surgery and/or radiotherapy High-grade truncal or head and neck sarcoma At least 10 cm in greatest dimension or any size with no surgical options for clear margins Primary site controlled by surgery and/or radiotherapy Locally recurrent disease in CR or PR after surgery, chemotherapy, or radiotherapy Metastatic STS in CR or PR after surgery, chemotherapy, or radiotherapy Osteosarcoma (OS) Extremity OS after neoadjuvant chemotherapy and surgical resection provided: Less than 50% necrosis in the surgical specimen LDH or alkaline phosphatase greater than 2 times normal at presentation Axial OS in CR or PR after chemotherapy and/or surgery Primary or recurrent metastatic OS in CR or PR after chemotherapy, surgery, and/or radiotherapy Ewing's sarcoma or primitive neuroectodermal tumor Primary site in CR or PR after chemotherapy, radiotherapy, or surgery Rib, pelvic, or axial skeleton primary Bulky tumor (at least 10 cm in greatest diameter) Primary or recurrent metastatic disease in CR or PR after surgery, chemotherapy, or radiotherapy Rhabdomyosarcoma Gross residual disease after primary treatment with surgery, chemotherapy, and radiotherapy Primary group IV or recurrent metastatic disease in CR or PR after chemotherapy and radiotherapy with or without surgery No brain metastasis No histologically confirmed bone marrow metastasis Prior metastases allowed with clearing of bone marrow at entry No contraindication to collection of mobilized stem cells or, if needed, autologous bone marrow
PATIENT CHARACTERISTICS: Age: 10 to 55 Performance status: Karnofsky 80-100% Hematopoietic: Absolute neutrophil count greater than 2,000/mm3 Platelet count greater than 150,000/mm3 Hemoglobin greater than 10 g/dL Hepatic: See Disease Characteristics Bilirubin less than 1.5 mg/dL AST and ALT less than 3 times normal Hepatitis B surface antigen negative Negative hepatitis C antigen test required in patients with hepatitis C antibody Renal: Creatinine less than 1.4 mg/dL Creatinine clearance greater than 75 mL/min Cardiovascular: LVEF at least 55% by MUGA or echocardiogram No history of significant cardiac disease Pulmonary: FEV1 greater than 2 liters PaO2 greater than 70 mm Hg on room air PaCO2 less than 42 mm Hg on room air DLCO greater than 60% predicted Other: No hearing loss of greater than 40 decibels HIV negative No organic or psychiatric CNS dysfunction that would preclude study No other medical or psychosocial problems that would place patient at unacceptable risk No history of other malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix Not pregnant Negative pregnancy test Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY: More than 2 weeks since treatment to control primary or recurrent tumor Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No more than 2 prior chemotherapy regimens (including adjuvant therapy) Prior cumulative cisplatin dose less than 400 mg/m2 Prior cumulative doxorubicin dose less than 240 mg/m2 Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics No prior radiotherapy to more than 20% of the bone marrow-containing axial skeleton No prior radiotherapy to the left chest wall Surgery: See Disease Characteristics
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| Name | Affiliation | Role |
|---|---|---|
| George Somlo, MD | City of Hope Medical Center | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cancer Center and Beckman Research Institute, City of Hope | Duarte | California | 91010-3000 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT | Cycle 1 Day -8 through Day -4 (96h) Doxorubicin 150 mg/m2 (CI) + Ifosfamide 14 g/m2 mixed with mesna (CI) Day -3 Mesna 3.5 g/m2 over 24 h Day -2 12.5% of stem cell reinfused. Cycle2 Day -11 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -10 thru Day -6 G-CSF 5ug/kg Day -4 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -3 12.5% if stem cell reinfused Day 0 37.5% of stem cell reinfused |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT | Cycle 1 Day -8 through Day -4 (96h) Doxorubicin 150 mg/m2 (CI) + Ifosfamide 14 g/m2 mixed with mesna (CI) Day -3 Mesna 3.5 g/m2 over 24 h Day -2 12.5% of stem cell reinfused. Cycle2 Day -11 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -10 thru Day -6 G-CSF 5ug/kg Day -4 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -3 12.5% if stem cell reinfused Day 0 37.5% of stem cell reinfused |
| 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 | Number of Participants With Grade 3 Bilirubin | Criteria for early termination of this feasibility study: > 2 patients experience grade 4 or 5 hematologic toxicity or more that 3 patients experience grade 3 hematologic toxicity; > 2 patients experience grade 3 hepatic or gastrointestinal toxicity or > 3 patients are unable to receive the second cycle of treatment; > 2 patients experience grade 5 toxicity related to treatment regimen. | Posted | Number | participants with Grade 3 Bilirubin | 2 years after completion of treatment |
|
Adverse events collected over a period of 45 months
"Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
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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 | Doxorubicin/Ifosfamide + Melphalan/CDDP + PSCT | Cycle 1 Day -8 through Day -4 (96h) Doxorubicin 150 mg/m2 (CI) + Ifosfamide 14 g/m2 mixed with mesna (CI) Day -3 Mesna 3.5 g/m2 over 24 h Day -2 12.5% of stem cell reinfused. Cycle2 Day -11 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -10 thru Day -6 G-CSF 5ug/kg Day -4 Melphalan 75 mg/m2 + Cisplatin 100 mg/m2 Day -3 12.5% if stem cell reinfused Day 0 37.5% of stem cell reinfused |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dysrhythmias | Cardiac disorders | COH | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cerebellar | Nervous system disorders | COH | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Paul Frankel, Ph.D. | City of Hope | (626)256-4673 | 65265 | pfrankel@och.org |
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| ID | Term |
|---|---|
| D012509 | Sarcoma |
| D012516 | Osteosarcoma |
| D012208 | Rhabdomyosarcoma |
| D018241 | Neuroectodermal Tumors, Primitive, Peripheral |
| ID | Term |
|---|---|
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D018213 | Neoplasms, Bone Tissue |
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| ID | Term |
|---|---|
| D000069585 | Filgrastim |
| D002945 | Cisplatin |
| D004317 | Doxorubicin |
| D007069 | Ifosfamide |
| D008558 | Melphalan |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| ID | Term |
|---|---|
| D016179 | Granulocyte Colony-Stimulating Factor |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
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| cisplatin | Drug | Course 2 - 100 mg/m2 at an infusion rate of 25 mg/hr |
|
| doxorubicin hydrochloride | Drug | Course 1 - 150 mg/m2 by continuous intravenous infusion for 96 hours. |
|
| ifosfamide | Drug | Course 1 - 14 gm/M2 by continuous intravenous infusion for 96 hours. |
|
| melphalan | Drug | Course 2 - 75 mg/m2 infused at a rate of 5 mg/minute |
|
| peripheral blood stem cell transplantation | Procedure | Administered on Day 0 following high-dose chemotherapy in both courses 1 and 2 |
|
| 5-year Overall Survival |
Estimated using the product-limit method of Kaplan and Meier. |
| Until death from any cause, up to 5 years |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Primary | Toxicities Counts | Number of patients with grade 3 and 4 toxicities observed during cycles 1 & 2 using the Common Toxicity Criteria Version for Chemotherapy. | Posted | Count of Participants | Participants | 2 months after completion of second cycle of treatment. |
|
|
|
| Secondary | 5-year Progression-free Survival | Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 25% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions. | Posted | Number | 95% Confidence Interval | percentage of participants | Until disease progression, up to 5 Years |
|
|
|
| Secondary | 5-year Overall Survival | Estimated using the product-limit method of Kaplan and Meier. | Posted | Number | 95% Confidence Interval | percentage of participants | Until death from any cause, up to 5 years |
|
|
|
| 3 |
| 13 |
| 13 |
| 13 |
| Pulmonary | Respiratory, thoracic and mediastinal disorders | COH | Non-systematic Assessment |
|
| Partial Thromboplastin Time | Investigations | COH | Non-systematic Assessment |
|
| Clinical (Physical Exam) | General disorders | COH | Non-systematic Assessment |
|
| Dysrhythmias | Cardiac disorders | COH | Non-systematic Assessment |
|
| Fluid Retention | Renal and urinary disorders | COH | Non-systematic Assessment |
|
| Hemorrhage | General disorders | COH | Non-systematic Assessment |
|
| Infection | Infections and infestations | COH | Non-systematic Assessment |
|
| Ischemia | Vascular disorders | COH | Non-systematic Assessment |
|
| Other Misc | General disorders | COH | Non-systematic Assessment |
|
| Pericardial | Cardiac disorders | COH | Non-systematic Assessment |
|
| Pulmonary | Respiratory, thoracic and mediastinal disorders | COH | Non-systematic Assessment |
|
| Stomatitis | General disorders | COH | Non-systematic Assessment |
|
| Weight (Food Intake) | Metabolism and nutrition disorders | COH | Non-systematic Assessment |
|
| Clinical Coagulation | Blood and lymphatic system disorders | COH | Non-systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | meddra9.0 | Non-systematic Assessment |
|
| EF/CHF | Cardiac disorders | COH | Non-systematic Assessment |
|
| Ear disorder | Ear and labyrinth disorders | meddra9.0 | Non-systematic Assessment |
|
| Hearing | Ear and labyrinth disorders | COH | Non-systematic Assessment |
|
| Eye disorder | Eye disorders | meddra9.0 | Non-systematic Assessment |
|
| Vision | Eye disorders | COH | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | COH | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | meddra9.0 | Non-systematic Assessment |
|
| Mucositis oral | Gastrointestinal disorders | meddra9.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | meddra9.0 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | meddra9.0 | Non-systematic Assessment |
|
| Chills | General disorders | meddra9.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | COH | Non-systematic Assessment |
|
| Fever (no infection) | General disorders | COH | Non-systematic Assessment |
|
| Allergy | Immune system disorders | COH | Non-systematic Assessment |
|
| AGC | Investigations | COH | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | meddra9.0 | Non-systematic Assessment |
|
| Alkaline Phosphatase | Investigations | COH | Non-systematic Assessment |
|
| Amylase | Investigations | COH | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | meddra9.0 | Non-systematic Assessment |
|
| Bilirubin | Investigations | COH | Non-systematic Assessment |
|
| Creatinine | Investigations | COH | Non-systematic Assessment |
|
| Creatinine increased | Investigations | meddra9.0 | Non-systematic Assessment |
|
| Fibrinogen | Investigations | COH | Non-systematic Assessment |
|
| Hyperbilirubinemia | Investigations | meddra9.0 | Non-systematic Assessment |
|
| Neutrophil count decreased | Investigations | meddra9.0 | Non-systematic Assessment |
|
| Partial Thromboplastin Time | Investigations | COH | Non-systematic Assessment |
|
| Platelet count decreased | Investigations | meddra9.0 | Non-systematic Assessment |
|
| Platelets | Investigations | COH | Non-systematic Assessment |
|
| Prothrombin Time | Investigations | COH | Non-systematic Assessment |
|
| SGOT/SGT | Investigations | COH | Non-systematic Assessment |
|
| WBC | Investigations | COH | Non-systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | meddra9.0 | Non-systematic Assessment |
|
| Hypercalcemia | Metabolism and nutrition disorders | COH | Non-systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | meddra9.0 | Non-systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | meddra9.0 | Non-systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | COH | Non-systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | meddra9.0 | Non-systematic Assessment |
|
| Cortical/State of Consciousness | Nervous system disorders | COH | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | meddra9.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | meddra9.0 | Non-systematic Assessment |
|
| Motor Activity | Nervous system disorders | COH | Non-systematic Assessment |
|
| Peripheral Nervous System Sensory | Nervous system disorders | COH | Non-systematic Assessment |
|
| Peripheral motor neuropathy | Nervous system disorders | meddra9.0 | Non-systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | meddra9.0 | Non-systematic Assessment |
|
| Taste alteration | Nervous system disorders | meddra9.0 | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | meddra9.0 | Non-systematic Assessment |
|
| Ideation | Psychiatric disorders | COH | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | meddra9.0 | Non-systematic Assessment |
|
| Mood | Psychiatric disorders | COH | Non-systematic Assessment |
|
| Hematuria | Renal and urinary disorders | COH | Non-systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | COH | Non-systematic Assessment |
|
| Hiccough | Respiratory, thoracic and mediastinal disorders | meddra9.0 | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | COH | Non-systematic Assessment |
|
| Extensive Skin Rash | Skin and subcutaneous tissue disorders | COH | Non-systematic Assessment |
|
| Local Skin Rash | Skin and subcutaneous tissue disorders | COH | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | COH | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | COH | Non-systematic Assessment |
|
Not provided
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| D009372 | Neoplasms, Connective Tissue |
| D009217 | Myosarcoma |
| D009379 | Neoplasms, Muscle Tissue |
| D018242 | Neuroectodermal Tumors, Primitive |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D003520 | Cyclophosphamide |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D010078 | Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
| Neutropenia |
|
| Febrile neutropenia |
|
| Thrombocytopenia |
|
| Mucositis |
|
| Bacteremia/sepsis |
|
| Hyperglycemia |
|
| Pulmonary function impairment (FEV1) |
|
| Pulmonary infiltrates |
|
| Diarrhea |
|
| Arrhythmia |
|
| Hematuria |
|
| Mood |
|
| Elevated PTT |
|