OncoTrials - мониторинг клинических исследований

Описание

Aplastic anemia (AA) is a rare bone marrow failure syndrome with an annual incidence of about 0.74/100,000, affecting all ages but more common in the elderly. It`s divided into congenital and acquired forms, with the latter being more prevalent. The primary acquired form is linked to T lymphocyte activation and genetic factors. The best treatment is allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a near 90% cure rate. Sibling allo-HSCT is ideal but finding a match is challenging. For those who relapse after immunosuppressive therapy, haploidentical HSCT is a viable option despite risks like graft failure and GVHD. Advances in transplantation have made haplo-HSCT`s efficacy comparable to other methods. Recent studies suggest co-transplantation with umbilical cord blood cells can improve outcomes by hastening hematopoietic recovery and prognosis. Our study will evaluate the feasibility and safety of this approach in AA treatment, comparing it to sibling fully matched transplantation, with a focus on infection rates, GVHD incidence, TRM, and EFS, aiming to enhance treatment practices and benefit patients and the medical industry.

Критерии включения

• * A patient age of 14-70 years
• * Patients diagnosed with Severe Aplastic Anemia (SAA) or Transfusion-Dependent Non-Severe Aplastic Anemia (TD-NSAA) according to the Chinese Guidelines for the Diagnosis and Treatment of Aplastic Anemia (2022 Edition) and suitable for allo-HSCT
• * Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Критерии исключения

• * Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
• * Patients with any conditions not suitable for the trial (investigators` decision)

Описание

This is a multicenter, single-arm, non-interventional study (NIS) to confirm the safety and efficacy of eltrombopag in Anti-Thymocyte Globulin (ATG) treatment naive pediatric patients with aplastic anemia (AA).

Критерии включения

• * Patients whose legally acceptable representative has given written consent for cooperation in this survey prior to enrollment in this survey
• * Patients aged ≥ 6 years and /< 18 years at the start of treatment with eltrombopag
• * Pediatric patients with AA who receive eltrombopag for the first time in combination with ATG after the approval of additional dosage and administration for "ATG-naïve pediatric patients with AA"

Критерии исключения

• * Patients who have received ATG without concomitant use of eltrombopag
• * Patients with congenital AA
• * Patients with suspected or confirmed diagnosis of myelodysplastic syndrome (MDS) at the start of treatment with eltrombopag
• * Patients who have received any drug products containing the same ingredient as eltrombopag (including investigational products)

Описание

This research is being done to investigate the safety and effectiveness of Darzalex Faspro (daratumumab and hyaluronidase-fihj) (a monoclonal antibody that targets plasma cells that make antibodies) and whether it can lower donor specific antibodies (DSA) levels to low enough levels to permit patients to proceed with allogeneic peripheral blood transplant (alloBMT). Those being asked to participate have high DSA levels that puts those being asked to participate at high risk of rejecting the available donor`s blood stem cells and making those being asked to participate ineligible to receive a stem cell transplant.

Критерии включения

• 1. Participates must meet all other institutional criteria for the planned reduced intensity conditioning allogeneic peripheral blood stem cell transplant (RIC alloHSCT) as defined in Johns Hopkins BMT Policy; all potential non-cord blood donor sources are included: matched related, haploidentical, matched unrelated, mismatched unrelated.
• 2. Participants must be ≥18 years of age.
• 3. Participants must have adequate organ function for undergoing RIC allogeneic peripheral blood stem cell transplant, and for undergoing a clinical trial.
• a. Hematologic. i. White blood cell (WBC). ANC ≥ 500/mm3 (growth factor support allowed). ii. Hemoglobin. No specific cut-off. (PRBC transfusion allowed). iii. Platelets. Platelets ≥ 10,000/mm3 (platelet transfusion allowed). b. Liver. Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert`s syndrome or hemolysis), and Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) /< 5x Upper limit of normal (ULN) c. Renal. Serum creatinine ≤ 2.0 mg/dL. d. Cardiac. Left ventricular ejection fraction ≥ 35%. e. Pulmonary. FEV1 ≥ 50%.
• 4. Subjects are eligible if there are high levels of Donor Specific Antibody levels based on protocol specific scoring system regardless of prior attempts at standard desensitization.
• 5. Participants must have a no other readily available suitable alternative donor.
• 6. All potential Participants must be pre-approved by BMT faculty consensus.
• 7. Participants must have adequate willingness to participate in a clinical trial.

Критерии исключения

• 1. Previous exposure to Daratumumab-SC or other anti-CD38 therapy
• 1. Exposure to Daratumumab-SC or other anti-CD38 therapies (unless a re-treatment study)
• 2. Exposure to an investigational drug (including investigational vaccine) or invasive investigational medical device for any indication within 4 weeks or 5 pharmacokinetic half-lives, whichever is longer.
• 3. Focal radiation therapy within 14 days prior to beginning of planned RIC allogeneic peripheral blood stem cell transplant regimen with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma
• 2. Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) /< 50% of predicted normal. Note that FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is /< 50% of predicted normal.
• 3. Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate.
• 4. Known hypersensitivity or intolerance to boron or mannitol, sorbitol, corticosteroids, monoclonal antibodies or human proteins, or the excipients
• 5. Diagnosis of multiple myeloma or Amyloid light-chain (AL) amyloidosis
• 6. A planned myeloablative alloBMT or the planned use of bone marrow or cord blood as a stem cell source
• 7. History of HIV infection at any time in past.
• 8. Seropositive for hepatitis B (HBV) (defined by a positive test for hepatitis B surface antigen /[HBsAg/] positive, or antibodies to hepatitis B surface and/or core antigens /[antiHBs or antiHBc, respectively/] with hepatitis B virus /[HBV/]- DNA quantitation positive). Patients who are positive for antiHBs and/or antiHBc must have a negative polymerase chain reaction (PCR) for HBV-DNA quantitation result during screening. Patients with serologic findings suggestive of HBV vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior HBV vaccination do not need to be tested for HBV DNA by PCR. Those who are PCR positive will be excluded.
• 9. Seropositive for hepatitis C (except in the setting of a sustained virologic response (SVR), defined as aviremia at least 12 weeks after completion of antiviral therapy)
• 10. Clinically significant cardiac disease, including:
• 1. Myocardial infarction within 6 months before RIC alloHSCT or unstable or uncontrolled disease/condition related to or affection cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV)
• 2. Uncontrolled cardiac arrhythmia

Описание

This project aims to collect detailed clinical data, blood samples, and patient-reported outcomes from 2,600 lung transplant candidates, donors, and recipients at Lung Transplant Centers. The goal is to create a robust resource for various research objectives, including studying the impact of variations in donor and medical practices on clinical outcomes. The project also seeks to identify serum biomarkers associated with or predictive of specific post-transplant complications and conditions.

Критерии включения

• 1. Able to understand and provide informed consent
• 2. ≥ 18 years of age at the time of written informed consent
• 3. Anticipated listing or listed for a single or bilateral cadaveric donor lung transplant or having received a lung transplant within 30 days
• * Participants undergoing repeat lung transplantation or multi-organ transplantation are eligible if they meet the inclusion/exclusion criteria.

Критерии исключения

• 1. Unwillingness of a participant or legally authorized representative (LAR) to give written informed consent or comply with study protocol
• 2. Pregnancy or plans to become pregnant
• 3. Past or current medical problems or findings from physical examination or laboratory testing, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant`s ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Описание

This is an open label Comparative Effectiveness Research (CER) study in which patients will be randomized at the site level to Prospera surveillance or EMB surveillance in a 2:1 ratio (Prospera to EMB) at each site.

Subjects will be enrolled into the study while under evaluation for heart transplantation or on the transplant waiting list prior to heart transplantation. All subjects will follow the center`s standard of care surveillance schedule from transplant through 4 weeks post-transplantation. EMB during this phase is expected to occur roughly weekly or bi-weekly.

Study group assignment will take place at randomization. Subjects will be randomized 30 days (± 10 days) post-transplant to Prospera surveillance versus EMB surveillance in a 2:1 ratio. Rejection surveillance (Prospera Group and EMB Group) will be performed at times corresponding to the institutional standard of care schedule for rejection surveillance.

Критерии включения

• 1. Age 18 years or older at the time of signing informed consent.
• 2. Undergoing transplant evaluation or currently on the heart transplant waiting list and expected to receive a heart transplant.
• 3. Able to read, understand and provide written informed consent. If the patient is unable to sign informed consent, a legally authorized representative (LAR) can consent on behalf of the patient.
• 4. Able and willing to comply with the study visit schedule, study procedures and study requirements.

Критерии исключения

• 1. Concurrent multiple solid organ or tissue transplants.
• 2. Prior history of any organ or cellular transplantation.
• 3. Planned use of other commercially available or investigational cfDNA or gene expression profile assays for rejection surveillance.
• 4. Pregnant.
• 5. Hemodynamically unstable or other serious medical condition that may adversely affect the subject`s ability to participate in the study.

Описание

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. There are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). However, the study was performed in single-center and with very small sample size. Therefore, it should be further validated via multicenter study. In this multi-center study, we aim to further evaluate the safety and efficacy of this protocol.

Критерии включения

• * 1. Primary disease: hematological malignancies (AML, CML, MDS, lymphoma, etc.); 2. Graft failure after the first haploidentical stem cell transplantation; 3. Time from the first transplantation to the second transplantation is less than 180 days; 4. Age≥14 years.

Критерии исключения

• * 1. Active infections; 2. Active GVHD; 3. Organ dysfunction: hepatic injury (Tbil≥2ULN), renal injury (Cr≥1.5ULN), heart injury (EF%/<50% or symptomatic heart failure); 4. Eastern Cooperative Oncology Group (ECOG) score/>2; 5. Expected life time/<30 days; 5. Patients could not cooperate; 6. Other situations that are considered inappropriate for enrollment by the investigators,

Описание

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. We previously reported encouraging results with a novel Flu/Cy regimen. However, there are still around 20% patients developed delayed platelet recovery. We designed a modified regimen to further improve the hematopoietic reconstitution after second transplantation. This prospective, single-arm study aims to investigate the safety and efficacy of this modified regimen.

Критерии включения

• * 1.Primary disease: hematological malignancies(AML, CML, MDS, lymphoma, etc.); 2.Graft failure after first allogeneic stem cell transplantation; 3.Time from the first transplantation to the second transplantation is less than 180 days; 4. Age≥14 years.

Критерии исключения

• * 1. Active infections; 2. Active GVHD; 3. Organ dysfunction: hepatic injury (Tbil≥2ULN), renal injury (Cr≥1.5ULN), heart injury (EF%/<50% or symptomatic heart failure); 4. Eastern Cooperative Oncology Group (ECOG) score/>2; 5. Expected life time/<30 days; 5. Patients could not cooperate; 6. Other situations that are considered inappropriate for enrollment by the investigators,

Описание

This is a single-arm, open-label, single-center, phase I study. The primary objective is to evaluate the safety of CD7 CAR-T Bridging to allo-HSCT therapy for patients with severe aplastic anemia

Критерии включения

• * Chinese expert consensus on the diagnosis and treatment of aplastic anemia（2017）, Diagnosis of severe aplastic anemia ，1. The degree of bone marrow cell proliferation /< 25%, or 25%-50% but residual hematopoietic cells /< 30%；2. With pancytopenia (at least two of the following peripheral blood parameters) : (1) absolute neutrophil /<0.5×10/^9/L; (2) Platelet count/< 20×10/^9/L; (3) The absolute value of reticulocytes /<20×109/L;
• * Suitable donors (relatives) with allogeneic HSCT indications and at least haploid allogeneic transplantation;
• * Patients who are not suitable or unwilling to undergo traditional allogeneic hematopoietic stem cell transplantation;
• * creatinine clearance /> 60ml/min; without liver invasion, serum total bilirubin ≤ 1.5 times the upper limit of normal, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were both ≤ 3 times the upper limit of the normal range. If there is liver invasion, serum erythrambirubin ≤ 3 times the upper limit of normal, and serum ALT and AST are both ≤ 5 times the upper limit of the normal range;
• * Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
• * No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;
• * Estimated survival time ≥ 3 months;
• * ECOG performance status 0 to 1;
• * Females and males of childbearing potential must agree to use adequate contraception prior to study entry, during study participation, and for 6 months after infusion (the safety of this therapy for unborn children is not known and has unknown risks);
• * Those who voluntarily participated in this trial and provided informed consent

Критерии исключения

• * Allergy to pre-treatment measures；
• * Those with acute graft versus host disease (GvHD) or moderate to severe chronic GvHD within 4 weeks before screening; Those who have received systemic drug therapy for GvHD within 4 weeks before the reinfusion；
• * History of epilepsy or other central nervous system disorders；
• * Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
• * Less than 100 days after allogeneic hematopoietic stem cell transplantation；
• * Patients with HIV infection，Active infection of hepatitis B virus or hepatitis C virus，Uncured active infection；
• * The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
• * Received anti-cancer chemotherapy or other drug treatment within 2 weeks prior to screening;
• * Any condition that, in the opinion of the investigator, may increase the risk to the subject or interfere with the results of the study.

Описание

A phase II trial of a reduced intensity conditioned (RIC) allogeneic hematopoietic cell transplant (HCT) with post-transplant cyclophosphamide (PTCy) for idiopathic severe aplastic anemia (SAA), paroxysmal nocturnal hemoglobinuria (PNH), acquired pure red cell aplasia (aPRCA), or acquired amegakaryocytic thrombocytopenia (aAT) utilizing population pharmacokinetic (popPK)-guided individual dosing of pre-transplant conditioning and differential dosing of low dose total body irradiation based on age, presence of myelodysplasia and/or clonal hematopoiesis.

Критерии включения

• * Idiopathic Severe Aplastic Anemia (SAA), characterized by one of the following:
• 1. Refractory cytopenia(s), with 1+ of the following:
• 1. Platelets /<20,000/uL or transfusion dependent
• 2. Absolute neutrophil count /<500/uL without hematopoietic growth factor support
• 3. Absolute reticulocyte count /<60,000/uL AND bone marrow cellularity /<50% (with /< 30% residual hematopoietic cells)
• 2. Early myelodysplastic features (bone marrow (BM) blasts /<5%), without history of MDS/AML pre-treatment.
• 3. Idiopathic SAA with post-HCT graft failure (blood/marrow donor chimerism /<5%) requiring a 2nd allogeneic HCT
• * Paroxysmal Nocturnal Hemoglobinuria (PNH), including AA-PNH overlap syndrome, acquired pure red cell aplasia (aPRCA), or acquired amegakaryocytic thrombocytopenia (aAT), characterized by one of the following:
• 1. Refractory cytopenia(s), with 1+ of the following:
• 1. Platelets /<20,000/uL or transfusion dependent
• 2. Absolute neutrophil count /<500/uL without hematopoietic growth factor support
• 3. Absolute reticulocyte count /<60,000/uL or red cell transfusion dependent AND Bone marrow evidence of 1 to 3-lineage aplasia OR peripheral blood PNH clone />/= 10%
• 2. Early myelodysplastic features (bone marrow (BM) blasts /<5%) without history of MDS/AML pre-treatment.
• 3. Idiopathic PNH, aPRCA, or aAT with post-HCT graft failure (blood/marrow donor chimerism /<5%) requiring a 2nd allogeneic HCT
• * Adequate organ function within 30 days of conditioning regimen

Критерии исключения

• * Pregnant, breastfeeding or intending to become pregnant during the study. Persons of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days of the start of treatment
• * Uncontrolled infection
• * Evidence of moderate or severe portal fibrosis or cirrhosis on biopsy
• * Known allergy to any of the study components
• * Prior radiation therapy deemed excessive by radiation therapist for proposed low dose TBI exposure on this protocol
• * Diagnosis of an inherited bone marrow failure disorder such as Fanconi anemia, Telomere biology disorder, or Schwachman-Diamond syndrome, unless reviewed by the principal investigator and deemed appropriate for this approach (e.g. GATA2 deficiency)
• * Advanced myelodysplastic syndrome (MDS; BM blasts />5%) or acute myeloid leukemia
• * Psychiatric illness/social situations that, in the judgement of the enrolling Investigator, would limit compliance with study requirements
• * Other illness or a medical issue that, in the judgement of the enrolling Investigator, would exclude the patient from participating in this study

Описание

The purpose of this study is to find out whether upfront emapalumab treatment can help in sAA (Aplastic Anemia) treatment planning and increase the effectiveness of standard treatment options.

Критерии включения

• * Patients undergoing workup for suspected newly diagnosed sAA:
• * Patients with severe cytopenias and a hypocellular marrow concerning for sAA
• * Patients that meet the definition for suspected sAA (Camitta Criteria) as follows:
• Marrow Cellularity: /<25%, or 25-50% with /<30% residual hematopoietic cells Peripheral cytopenias (at least 2 of 3) Absolute neutrophil count (ANC): /<500 x 10/^9/L Platelets: /<20 x 10/^9/L Absolute Reticulocyte Count: /<60 x 10/^9/L
• * Patients that do not have evidence of leukemia or MDS
• * Patients /< 25 years of age at time of diagnosis
• * Able to tolerate emapalumab and IST (with standard institutional organ function criteria)

Критерии исключения

• * Uncontrolled infection at presentation.
• * Patients who have undergone previous treatment for sAA.
• * Patients with known inherited bone marrow failure
• * Patient who has completed a full workup for sAA including having results back from telomere testing, DEB and genetics (when applicable), as well as having an appropriate willing and available donor and would otherwise be admitted for HSCT within 2 weeks of enrolling on the trial
• * Patients with leukemia or MDS
• * Patient or parent or guardian unable to give informed consent or unable to comply with the treatment protocol including research tests.

Описание

A single-center, randomized, double-blinded placebo-controlled trial is proposed to investigate administration of supraphysiologic doses of ascorbic acid (vitamin C, AA) to patients undergoing liver transplantation. Participants randomized to the intervention group will receive intravenous (IV) AA 1500 mg every 6 hours for 48 hours. Participants randomized to the control group will receive a saline placebo. The primary study outcome will be a change in the Sequential Organ Failure Assessment (SOFA) score from baseline to three days after the first dose of drug (dSOFA3). Secondary outcomes will include total vasopressor dose in norepinephrine equivalents, 30-day and 1-year mortality, and serum AA levels.

Критерии включения

• * The subject is scheduled to undergo primary deceased donor solidary liver transplantation

Критерии исключения

• * Non-English speaking
• * Known or believed to be pregnant
• * Subject is a prisoner
• * Impaired decision-making capacity (i.e., current encephalopathy)
• * Known allergy to AA
• * Concurrent organ transplantation (i.e., simultaneous liver-kidney transplantation)
• * Planned veno-venous bypass use in the operating room
• * Prior parenteral or oral AA repletion
• * History of nephrolithiasis or oxaluria
• * Vitamin C supplement use or administration (including HAT therapy) within the last month prior to transplantation
• * Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• * Sickle cell anemia
• * Hereditary hemochromatosis
• * Preoperative anuria or creatinine />2.5mg/dL in patient not on renal replacement therapy
• * Current enrollment in another research study

Описание

This phase I trial evaluates the safety and feasibility of using a reduced-intensity regimen of cyclophosphamide, pentostatin, and anti-thymocyte globulin prior to a CD4+ T-cell depleted haploidentical hematopoietic cell transplant (haploHCT) for the treatment of patients with severe aplastic anemia that does not respond to treatment (refractory) or that has come back (recurrent). Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell`s deoxyribonucleic acid. It may also lower the body`s immune response. Pentostatin blocks a protein needed for cell growth. Anti-thymocyte globulin is an immunosuppressive drug can destroy immune cells known as T-cells. HaploHCT transfers blood-forming stem cells from a healthy partially-matched donor to a patient. Administering a regimen of cyclophosphamide, pentostatin, and anti-thymocyte globulin before haploHCT may help make room for the new, healthy cells and may reduce the risk of graft versus host disease.

Критерии включения

• * RECIPIENT: Documented informed consent of the participant.
• * RECIPIENT: Age: />= 40 years but =/< 75 years of age at time of enrollment.
• * RECIPIENT: Failed at least one trial of immunosuppressive therapy (IST) by being refractory (persistence of severe cytopenia and fulfillment of SAA disease criteria at least 3 months after initial IST) or having relapsed (initial improvement of cytopenia after first-line IST but then a later return to fulfillment of SAA disease criteria when IST is decreased or ceased). IST could have included anti-thymocyte globulin (ATG) based regimens, calcineuPririn inhibitors and/or other higher dose therapy directed at the treatment of primary SAA.
• * RECIPIENT: Karnofsky performance score />= 60%.
• * RECIPIENT: Confirmed diagnosis of severe aplastic anemia as:
• * Bone marrow cellularity /< 25% or marrow cellularity /< 50% but with /< 30% residual hematopoietic cells;
• * Two out of three of the following (in peripheral blood):
• * Neutrophils /< 0.5 x 10/^9/L;
• * Platelets /< 20 x 10/^9/L;
• * Reticulocyte count /< 20 x 10/^9/L (/< 60 x 10/^9/L using an automated analysis).
• * RECIPIENT: No suitable fully matched related sibling donor (6/6 match for human leukocyte antigen /[HLA/]-A and B at intermediate or high resolution and DRbetaA1 at high resolution using deoxyribonucleic acid /[DNA/]-based typing) available.
• * RECIPIENT: Available relative of the patient who is a haploidentical match, including biological parents, siblings or half siblings, children, uncles/aunts, first cousins, etc. Eligible haploidentical donors will have 2-4 mismatches if HLA-A, -B, -C, and -DRB1 typing is used; 2-5 mismatches if HLA-A, -B, -C, -DRB1, and -DQB1 typing is used; and 2-6 mismatches if HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 typing is used. A unidirectional mismatch in either the graft versus host or host versus graft direction is considered a mismatch. The donor and recipient must demonstrate that they are a full haplotype match by being identical at a minimum of one allele (at high resolution DNA-based typing) at the following genetic loci: HLA-A, -B, -C, and DRB1 if 8 allele typing is used; HLA-A, -B, -C, -DRB1, and -DQB1 if 10 allele typing is used; and HLA-A, -B, -C, -DRB1-, DQB1, and -DPB1 is 12 allele typing is used by the local center.
• * RECIPIENT: Patient and/or legal guardian must sign informed consent for the hematopoietic stem cell transplantation (HSCT).
• * RECIPIENT: The haplo donor and/or legal guardian must be able to sign informed consent documents.
• * RECIPIENT: The potential haplo donor must be willing and able to donate bone marrow.
• * RECIPIENT: The weight of the haplo donor must be />= 20 kg.
• * RECIPIENT: Total bilirubin /< 3.0 x the upper limit of normal (ULN) for age (patients who have been diagnosed with Gilbert`s Disease are allowed to exceed this limit)
• * RECIPIENT: Aspartate aminotransferase (AST) =/< 5.0 x ULN.
• * RECIPIENT: Alanine transaminase (ALT) =/< 5.0 x ULN.
• * RECIPIENT:
• * For patients />= 13.0 years of age at the time of enrollment: Creatinine clearance of />= 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula.
• * For patients /< 13 years of age at enrollment: Glomerular filtration rate (GFR) estimated by the updated Schwartz formula /> 90 mL/min/1.73 m/^2. If the estimated GFR is /< 90 mL/min/1.73m/^2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be /> 50mL/min/1.73m/^2.
• * RECIPIENT: Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• * RECIPIENT: Echocardiogram (ECHO) or multigated acquisition (MUGA): Left ventricular ejection fraction (LVEF) at rest />= 40%. For patients aged /< 13 years, shortening fraction (SF) />= 26% by echocardiogram or MUGA may be substituted for LVEF.
• * RECIPIENT:
• * For patients /> 13.0 years of age: Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected/adjusted for hemoglobin) /> 40% and forced expiratory volume in 1 second (FEV1) /> 50% predicted (without administration of bronchodilator) and forced vital capacity (FVC) /> 50% predicted.
• * For patients /< 13.0 years of age unable to perform pulmonary function tests (PFTs) due to age or developmental ability: (1) no evidence of dyspnea at rest and (2) no need for supplemental oxygen and (3) oxygen (O2) saturation /> 92% on room air at sea level (with lower levels allowed at higher elevations per established center standard of care /[e.g., Utah, 4,200 feet above sea level, does not give supplemental oxygen unless below 90%/]).
• * RECIPIENT: Seronegative for human immunodeficiency virus (HIV) antigen and antibody (Ag/Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin /[RPR/])
• * If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed.
• * RECIPIENT: Antibodies to donor red blood cell antigens including ABO and rhesus (Rh) meets institutional titer requirements.
• * RECIPIENT: WOCBP or sexually active male: Agreement to use adequate contraception prior to study entry and 6 months post-CD4+ T-cell-depleted-HaploHCT.
• * DONOR: Documented protocol-specific City of Hope (COH) informed consent per local, state and federal guidelines
• * DONOR: Documented general institutional informed consent per local, state and federal guidelines.
• * DONOR: Age: younger than 60 years.
• * DONOR: Haplo donor selection is based on HLA typing and relationship to recipient.
• * DONOR: When more than one donor is available, the donor with the lowest number of HLA allele mismatches will be chosen unless there is HLA cross-match incompatibility or a medical reason to select otherwise. In cases where there is more than one donor with the least degree of mismatch, donors will be selected based on the most favorable combination of HLA compatibility in cross-match testing and ABO compatibility. Prioritization is given to the lowest number of mismatches in the host-versus-graft (HVG) direction to minimize the risk of graft failure.
• * DONOR: If there is more than one donor with the least amount of host-versus-graft (HVG) allele mismatches, the suggested prioritization in order of importance includes ABO compatibility, cytomegalovirus (CMV) status (use a sero-negative donor for a sero-negative recipient or use a sero-positive donor for a sero-positive recipient), younger age and lighter weight (this rule applies down to the age of 18, however, children may also be used as donors if appropriate), and sex of the donor (if all else is equal, males are preferred over nulliparous females over multiparous females).
• * DONOR: Infectious disease screening performed within 30 days prior to stem cell collection and per federal guidelines and is:
• * Seronegative for HIV Ag, HIV 1+2 Ab, human T-lymphotropic virus (HTLV) I/II Ab, hepatitis B virus surface antigen (HBsAg), hepatitis B virus core antibody (HBcAb) (immunoglobulin M /[IgM/] and immunoglobulin G /[IgG/]), HCV Ab;
• * Negative RPR for syphilis.
• * DONOR: WOCBP: Urine pregnancy testing performed within 7 days prior to stem cell mobilization
• * DONOR: Is approved and completed evaluation per institutional guidelines.

Критерии исключения

• * RECIPIENT: Inherited and acquired (non-aplastic anemia) bone marrow failure syndromes such as Fanconi anemia must be ruled out according to center standards.
• * RECIPIENT: Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination (e.g. Monosomy 7).
• * RECIPIENT: Any somatic mutations (including TERT, TERC, DKC1, NOP10) other than PIG-A (PNH) or BCOR mutation.
• * RECIPIENT: Diagnosis of myelodysplastic syndrome (MDS).
• * RECIPIENT: Presence of anti-donor HLA antibodies (positive anti-donor HLA antibody is defined as a positive cross-match test of any titer by complement-dependent cytotoxicity or flow cytometric testing or the presence of anti-donor HLA antibody to the high expression loci HLA-A, B, C, DRB1, or DPB1 with mean fluorescence intensity /[MFI/] /> 1000 by solid phase immunoassay).
• * RECIPIENT: Prior allogeneic stem cell transplant.
• * RECIPIENT: Prior solid organ transplant.
• * RECIPIENT: Known life-threatening reaction (i.e., anaphylaxis) to Thymoglobulin (registered trademark) that would prohibit use for the patient as this study requires use of the Thymoglobulin (registered trademark) preparation of ATG.
• * RECIPIENT: Uncontrolled bacterial, viral, or fungal infection at the time of enrollment. Uncontrolled is defined as currently taking medication and with progression or no clinical improvement on adequate medical treatment.
• * RECIPIENT: Seropositive for the human immunodeficiency virus (HIV).
• * RECIPIENT: Active hepatitis B or C determined by a detectable viral load of HBV or HCV.
• * RECIPIENT: Female patients who are pregnant (per institutional practice) or breast-feeding.
• * RECIPIENT: Prior malignancies except resected basal cell carcinoma 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 will not be allowed unless approved by the protocol chairs and/or protocol officer.
• * RECIPIENT: Alemtuzumab or ATG within 2 weeks of enrollment.
• * RECIPIENT: Any other condition that would, in the investigator`s judgment, contraindicate the patient`s participation in the clinical study due to safety concerns with clinical study procedures.
• * RECIPIENT: Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).
• * DONOR: Has undergone any transplantation (i.e. organ, stem cell, bone marrow, blood).
• * DONOR: Receiving any investigational agents, or concurrent biological, chemotherapy, immunosuppression or radiation therapy.
• * DONOR: Active infection.
• * DONOR: Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis.
• * DONOR: Factors which place the donor at increased risk for complications from leukapheresis or granulocyte colony-stimulating factor (G-CSF) therapy.
• * DONOR: WOCBP: pregnant or =/< 6 months breastfeeding.