Neoplasms

Blood and Lymph Conditions

All Conditions

Hematologic Neoplasms

Hematologic Diseases

Naive T Cell Depleted Donor Lymphocyte Infusion from HLA matched family member donor or 8/8 HLA matched unrelated donor.

A single naive T-cell depleted donor lymphocyte infusion will be administered through a peripheral or central venous catheter greater than or equal to 60 days post allogeneic hematopoietic stem cell transplant.

Naive T Cell Depleted Donor Lymphocyte Infusion

Mitchell Horwitz, MD

Allogeneic stem cell transplantation offers the hope of cure for a wide variety of hematologic malignancies. Mature donor T-cells play a critical role in the success or failure of this procedure and a subset of donor T-cells mediate graft-versus-host disease while other subsets provide the foundation for immune recovery. The major challenge in allogeneic stem cell transplantation is determining how to maximally exploit the beneficial effects mediated by T-cells without causing GvHD. This challenge could be overcome by selectively depleting the population of donor T-cells responsible for eliciting the GvHD response. The study hypothesis is depletion of naïve T-cells from the donor lymphocyte inoculum will not cause GVHD while providing T-cells to affect both anti-infection and anti-tumor responses.

Allogeneic stem cell transplantation (SCT) offers the hope of cure for a wide variety of hematologic malignancies. Mature donor T-cells play a critical role in the success or failure of this procedure. A subset of donor T-cells mediates graft-versus-host disease (GvHD). Other subsets provide the foundation for immune recovery. Pan-depletion of mature donor T-cells is an obligate step in haploidentical allogeneic stem cell transplantation. Without this step, the recipient would succumb to lethal acute GVHD. We have had extensive experience with in-vivo donor (and recipient) T-cell depletion using alemtuzumab as part of the bone marrow conditioning regimen. We and others have also used anti-thymocyte globulin for the same purpose. Pan-depletion of T-cells eliminates GvHD but significantly increases the risks of tumor relapse and opportunistic infections. A delayed donor lymphocyte infusion augments immune recovery and the graft versus tumor response, but it comes at the risk of inducing lethal GvHD. This is particularly problematic when the donor and recipient are HLA-discordant. Thus the major challenge in allogeneic stem cell transplantation is determining how to maximally exploit the beneficial effects mediated by T-cells without causing GvHD. This challenge could be overcome by selectively depleting the population of donor T-cells responsible for eliciting the GvHD response. We have been interested in selecting T-cells based on their naïve or memory phenotype to understand the contribution of each of these cells to the pathogenesis of GvHD. Naïve T-cells (CD62L+ or CD45RA+) are T-cells that have not encountered antigens specific for their T-cell receptor. Memory T-cells (CD62L- or CD62L+ or CD45RA-) are T-cells that have previously been exposed to their corresponding cognate antigens. If a donor has not encountered host alloantigens, GvHD-inducing host-reactive T-cells should be contained in the naïve T-cell compartment. In contrast, all the memory phenotype cells should not recognize host alloantigens. If this hypothesis is correct as suggested by several published studies, CD62L- T-cells, which are devoid of naïve T-cells and represent a subset of memory T-cells, should not be able to induce GvHD. The study hypothesis is depletion of naïve T-cells from the donor lymphocyte inoculum will abrogate GVHD while providing immunocompetent memory T-cells to affect an anti-infection and a graft versus tumor response. In this study, we will determine the maximum tolerated dose of a naïve T-cell depleted donor lymphocyte infusion given to patients following HLA-matched allogeneic stem cell transplantation. We will assess the GVHD-inducing potential of this donor lymphocyte infusion and further monitor the impact that this DLI will have on post-transplant immune recovery.

Naive T-Cell Depleted DLI Following Allo Stem Cell Transplant

Naive T-Cell Depleted Donor Lymphocyte Infusion Following Allogeneic Stem Cell Transplantation

To determine the maximum tolerated dose (MTD) of a Naive T cell depleted (TCD) donor lymphocyte infusion (DLI) post alemtuzumab-containing allogeneic transplant procedure from a HLA-identical family donor, or an 8/8 HLA-matched unrelated donor and derive a preliminary assessment of the efficacy of the naive T-cell depleted DLI.

Immunological recovery will be assessed by the immune function panel which consists of a standardized panel of T-cell, B-cell, NK-cell, and dendritic cell antibodies, measurement of T-cell function, analysis of B-cell recovery, quantification of Naive T-cell recovery and a T-cell repertoire assay.

To assess the overall incidence of Acute Graft Versus Host Disease

To assess the overall incidence of opportunistic infections

To assess overall incidence of Chronic Graft Versus Host Disease

Principal Investigator

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Rare Diseases

Syndrome

Carcinoma

Carcinoma, Renal Cell

Graft vs Host Disease

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Homologous Wasting Disease

Engraftment Syndrome

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Dermatologic Agents

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Cyclophosphamide

Cyclosporine

Cyclosporins

Sirolimus

Temsirolimus

MTOR Inhibitors

Pentostatin

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Enzyme Inhibitors

Adenosine

A sibling who is 6/6 HLA --matched with the recipient. Donors undergo donor lymphocyte harvest and stem cell mobilization and harvest.

Recipients undergo induction therapy, allogeneic stem cell therapy and GVHD prophylaxis.

Pentostatin: 2- 4mg/m\^2(CrCL based dosing) intravenous (IV) on days 1, 8, and 15

Sirolimus: 4 mg by mouth (PO) on days -3 to +7 post-transplant (No Sirolimus administered after day 7 post-stem cell transplant (SCT))

Cyclosporine: 2 mg/kg every 12 hours PO or IV starting on day -4 of hematopoietic stem cell transplant (HSCT)

Allogeneic Hematopoietic Stem Cell Transplant

Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

Th2 rapa cells

Donor Lymphocyte Harvest

Pentostatin and cyclophosphamide (PC) conditioning regimen.

Induction Therapy

Short course of sirolimus plus maintenance therapy with sirolimus A.

GVHD prophylaxis

Following lymphocyte harvest, donors for recipients will undergo stem cell mobilization and harvest.

Donor Hematopoietic Stem Cell Harvest

Daniel H Fowler, M.D.

Background:

Low-dose chemotherapy is easier for the body to tolerate than typical high-dose chemotherapy and involves a shorter period of complete immune suppression.

Donor immune cells called lymphocytes, or T cells, fight residual tumor cells that might have remained in the recipients body after stem cell transplant, in what is called a graft-versus-tumor (GVT) effect.

The immune-suppressing drug sirolimus appears to help prevent graft-versus-host disease (GVHD), a side effect of stem cell transplant in which donated T cells sometimes attack healthy tissues, damaging organs such as the liver, intestines and skin.

Th2 cells are cells collected from the transplant donor and grown in a high concentration of sirolimus.

Objectives:

To determine whether stem cell transplantation using low-dose chemotherapy and sirolimus-generated Th2 cells can cause a remission of advanced kidney cancer.

Eligibility:

Patients between 18 and 75 years of age who have kidney cancer that has spread beyond the kidney and who have a tissue-matched sibling stem cell donor.

Design:

Patients undergo stem cell transplantation as follows:

* Low-intensity chemotherapy with pentostatin and cyclophosphamide over a 21-day period to reduce the level of the immune system to prepare for the transplant. Pentostatin is given through a vein (intravenous (IV)) on days 1, 8 and 15; cyclophosphamide tablets are taken by mouth for 21 consecutive days.
* Sirolimus tablets, taken by mouth, starting 2 days before the transplant and continuing until 60 days after the transplant.
* IV infusions of stem cells and Th2 cells.

Following the transplant, patients have the following procedures:

* Additional Th2 cell infusions on days 14 and 45 after the transplant.
* Follow-up visits at the National Institutes of Health (NIH) Clinical Center twice a week for the first 6 months after the transplant and then less frequently for at least 5 years to evaluate response to treatment and treatment side effects. Evaluations include a bone marrow aspirate and biopsy 1 month after transplant and periodic blood tests and imaging procedures (e.g., computed tomography (CT) or magnetic resonance imaging (MRI) scans).

Background:

Allogeneic hematopoietic stem cell transplantation (HSCT) represents a potentially effective treatment option for patients with metastatic renal cell carcinoma (RCC).

In a pilot clinical trial in refractory hematologic malignancy subjects, we have found that augmentation of a T cell-replete allograft with donor Th2 cells generated ex vivo in sirolimus (rapamycin; Th2.rapa cells) allows prompt donor engraftment after outpatient-intensity chemotherapy. This transplant approach has been associated with a low incidence of acute graft versus host disease (GVHD).

Based on these data, we seek to safely achieve objective clinical regression of metastatic RCC by the following new transplant approach. (1) The allograft will be administered after a low intensity, outpatient induction chemotherapy regimen consisting of pentostatin and cyclophosphamide. This regimen is intended to provide sufficient host immune T cell depletion, and as such, a conventional preparative regimen will not be administered. (2) To avoid mixed chimerism for rapid potentiation of graft-versus-tumor (GVT) effects, a growth colony stimulating factor (G-CSF) mobilized allograft will be augmented with donor lymphocyte infusion at day 14 post-transplant consisting of Th2.rapa cells.

Objectives:

Primary objective: (1) Determine whether this new, low-intensity transplant approach can yield objective partial or complete remission of metastatic RCC, with the goal of ruling out a partial response (PR)/complete response (CR) rate of 20% in favor of a rate of 60%.

Secondary objectives: (1) Evaluate the safety and immune-depleting properties of the pentostatin/cyclophosphamide regimen; (2) Characterize the engraftment kinetics and GVHD profile of this new transplant approach; and (3) Characterize post-transplant immunity in study subjects, including cytokine phenotype, immune reconstitution, and potential anti-tumor effector mechanisms.

Eligibility:

Adults (18 - 75 years) with metastatic RCC who have an eligible 6/6 human leukocyte antigen (HLA)-matched sibling donor.

Must have had one prior therapy with either sorafenib, sunitinib, or temsirolimus or any other Food and Drug Administration (FDA)-approved agent for therapy of metastatic renal cell carcinoma..

Life expectancy greater than or equal to 3 months, Karnofsky score greater than or equal to 80, relatively normal organ function, and absence of central nervous system (CNS) metastases.

Design:

Patients will receive a 21-day course of pentostatin (intravenous infusion on days 1, 8, and 15; 4 mg/m\^2 per dose) and daily oral cyclophosphamide (200 mg per day).

Patients will receive a mobilized, T cell-replete allogeneic hematopoietic stem cell graft followed by a pre-emptive donor lymphocyte infusion with donor Th2 cells at day 14 post-transplant. GVHD prophylaxis will consist of a short-course of sirolimus plus maintenance therapy with cyclosporine A.

If greater than or equal to 2/5 partial or complete responses are observed within 6 months post-transplant, the therapy will be considered potentially promising, and will be expanded in a Simon two-stage design to evaluate a total of n = 14 subjects. If greater than or equal to 5/14 PR/CR are achieved, the therapy will be considered worthy of further investigation.

Low-Intensity Stem Cell Transplantation With Multiple Lymphocyte Infusions to Treat Advanced Kidney Cancer

Low Intensity Allogeneic Hematopoietic Stem Cell Transplantation Therapy of Metastatic Renal Cell Carcinoma Using Early and Multiple Donor Lymphocyte Infusions Consisting of Sirolimus-Generated Donor Th2 Cells

Response was assessed by computed tomography measurements and the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest LD recorded since the treatment started or the appearance of one or more new lesions.

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

Absolute neutrophil count determination by complete blood count methodology (Absolute Neutrophil Count (ANC) \< 500 Cells/µL).

Occurrence of infection by Common Terminology Criteria for Adverse Events (CTCAE).

Reduction in cluster of differentiation 4 (CD4)+ T cells \[change in median values and (range of values)\].

Reduction in cluster of differentiation 8 (CD8)+ T cells \[change in median values and (range of values)\].

Immune suppression is defined by the frequency of elimination of a pre-transplant T cell cytokine value.

Donor Genetic Elements by variable number tandem repeat-polymerase chain reaction (VNTR-PCR) Analysis.

Acute GVHD is assessed by the 1994 Consensus Conference on Acute GVHD grading criteria. Acute GVHD may include rash, diarrhea, and liver damage (i.e. rash Grading: \<25% body surface area (BSA) = 1, rash 25-50% BSA = 2, generalized erythroderma = 3, and desquamation and bullae = 4); liver Grading: total bilirubin 2-3 mg/dl = 1, total bilirubin 3-6 mg/dl =2, total bilirubin 6-15 mg/dl =3, and total bilirubin \>15 mg/dl = 4)).

Acute GVHD is assessed by the 1994 Consensus Conference on Acute GVHD grading criteria. Acute GVHD is assessed by the 1994 Consensus Conference on Acute GVHD grading criteria. Acute GVHD may include rash, diarrhea, and liver damage (i.e. rash Grading: \<25% body surface area (BSA) = 1, rash 25-50% BSA = 2, generalized erythroderma = 3, and desquamation and bullae = 4); liver Grading: total bilirubin 2-3 mg/dl = 1, total bilirubin 3-6 mg/dl =2, total bilirubin 6-15 mg/dl =3, and total bilirubin \>15 mg/dl = 4)).

Chronic GVHD was assessed by the 2005 Chronic GVHD Consensus Project. Chronic GVHS may include dryness of the mouth and eyes, weight loss, liver damage and lung damage leading to cough and shortness of breath (i.e. skin Grading: no symptoms = 0, \<18% body surface area (BSA) = 1, 19-50% BSA = 2, and \>50% BSA = 3); oral cavity Grading: no symptoms = 0, mild symptoms = 1, moderate symptoms =2 and severe symptoms =3)).

CD4 T Cells immune reconstitution is defined as distribution of CD4+ T cells subsets within naïve, central memory, effector memory, and effector memory-RA cells analyzed by flow cytometry.

CD8+ T Cells immune reconstitution is defined as distribution of CD8+ T cells subsets within naïve, central memory, effector memory, and effector memory-RA cells analyzed by flow cytometry.

Intra-cellular flow cytometry detection of GATA3 transcription factor.

CD4+ T cells were analyzed by flow cytometry for intracellular detection of Tbet transcription factor.

CD4+ T cells were analyzed by flow cytometry for intracellular expression of FoxP3.

National Cancer Institute (NCI)

Donor

Recipient

Donors

Recipients

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Daniel Fowler

Partial Response (PR)

Complete Response (CR)

Progressive Disease (PD)

Stable Disease (SD)

Not Applicable (NA)

Clinical Regression of Metastatic Renal Cell Carcinoma (Partial Response (PR)) or Complete Remission of Tumor (Complete Response (CR))

Count of Participants With Adverse Events

Count of Patients Having Neutropenia Attributable to the Pentostatin and Cyclophosphamide (PC) Regimen

Count of Patients Having an Infectious Complication Attributable to the Pentostatin and Cyclophosphamide (PC) Regimen

Baseline

Day 21

Immune Depletion in Cluster of Differentiation 4 (CD4) Cells

Immune Depletion in Cluster of Differentiation 8 (CD8)+ T Cells

Positive at baseline

Negative at baseline

Positive 24 hours after regimen

Negative 24 hours after regimen

Immune Suppression

Day 14 donor T cell chimerism

Day 28 donor T cell chimerism

Day 45 donor T cell chimerism

Day 60 donor T cell chimerism

Day 14 myeloid cell chimerism

Day 28 myeloid cell chimerism

Day 45 myeloid cell chimerism

Day 60 myeloid cell chimerism

Engraftment Donor T Cell and Myeloid Cell Chimerism

Count of Patients With Grade II or Greater Acute Graft Versus Host Disease (GVHD) in First 100 Days Post-Transplant

Only 6 patients were evaluable for this endpoint due to death due to malignancy.

Count of Patients With Late Acute Graft Versus Host Disease (GVHD) After Day 100 Post-Transplant

Only 4 patients were evaluable due to mortality from malignancy.

Count of Patients With Chronic Graft Versus Host Disease (GVHD)

Day 14

Day 60

Day 100

The values for each subset were stable at days 60 and 100 relative to day 14 values.

Cluster of Differentiation 4 (CD4) T Cells Immune Reconstitution

Cluster of Differentiation 8 (CD8)+ T Cells Immune Reconstitution

Percentage of Cluster of Differentiation 4 (CD4)+ T Cells Expressing the Th2 Transcription Factor GATA Binding Protein 3 (GATA-3)

Percentage of Cluster of Differentiation 4 (CD4)+ T Cells Expressing the Th1 Transcription Factor T-bet

Percentage of Cluster of Differentiation 4 (CD4)+ T Cells Expressing the T-reg Transcription Factor Forkhead Box P3 (FoxP3))

Allogeneic Stem Cell Therapy

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Prospectively enrolled cohort of patients receiving allogeneic hematopoietic cell transplantation for multiple myeloma

Historical cohort of patients with autologous hematopoietic cell transplantation between 2010 and 2016

This observational study will compare outcomes of prospectively enrolled HCT recipients with outcomes of a cohort of matched autoHCT controls.

Mona Patel

Michael Tierney

Anita D'Souza, MD, MS

Parameswaran Hari, MD, MS

Multiple myeloma (MM) is the second most common hematologic malignancy in adults. The current standard of care for MM patients fit to undergo high dose conditioning chemotherapy is an autologous HCT (autoHCT). Allogeneic HCT (alloHCT) is the only potentially curative therapy available to patients with MM. However, the significant morbidity and mortality of this procedure historically limited its application in older patients.

Thus, although potentially curative, standard risk MM patients have excellent prognoses in the era of novel therapies which reduces the overall benefit of alloHCT. However, because the outcomes for high-risk MM remain poor despite the best available standard therapies (overall survival of 24-36 months), initial data suggest that alloHCT should be explored in this subset.

Multiple myeloma (MM) is the second most common hematologic malignancy in adults. Overall survival (OS) in MM has improved significantly in the last 15 years with the emergence of novel therapies such as thalidomide, bortezomib and lenalidomide. The median life expectancy of patients with MM treated in the current era is more than 6 years, while SEER data from a slightly earlier time period (2008-12) estimated the 5 year survival at 48.5%. However, prognosis is not uniform and varies considerably based on a presenting features and response to therapy.

The current standard of care for MM patients fit to undergo high dose conditioning chemotherapy is an autologous HCT (autoHCT). There is controversy regarding the timing of autoHCT after initial novel therapy induction with randomized trials showing similar OS whether done early or delayed to time of relapse as salvage therapy. However, more recent trials comparing early versus delayed transplant support the benefit of early upfront autoHCT.

Allogeneic HCT (alloHCT) is the only potentially curative therapy available to patients with MM. However, the significant morbidity and mortality of this procedure historically limited its application in older patients. Current data from the Center for International Blood and Marrow Research (CIBMTR) show transplant-related mortality rates of 23 (20-26)% at 5 years with myeloablative conditioning.

Thus, although potentially curative, standard risk MM patients have excellent prognoses in the era of novel therapies which reduces the overall benefit of alloHCT. However, because the outcomes for high-risk MM remain poor despite the best available standard therapies (overall survival of 24-36 months), initial data suggest that alloHCT should be explored in this subset.

Assessment of Allogeneic Hematopoietic Cell Transplantation in Medicare Beneficiaries With Multiple Myeloma

Assessment of Allogeneic Hematopoietic Cell Transplantation in Medicare Beneficiaries With Multiple Myeloma: A Study to Develop Evidence of Effectiveness for the Centers for Medicare and Medicaid Services (CMS)

Compare five-year overall survival between the alloHCT cohort and an age and disease risk matched cohort of autoHCT patients

five-year PFS probabilities between the AlloHCT cohort and an age and disease risk matched cohort of autoHCT patients

Myeloma recurrence or progression will be defined per International Myeloma Working Group (IMWG) guidelines

Death from any cause within 28 days after alloHCT or death in the absence of progression/relapse of MM after day 28 post transplant

Occurrence of Grade I, II and III/IV skin, gastrointestinal, or liver abnormalities fulfilling the Consensus criteria of Grades II-IV acute GVHD

Occurrence of symptoms in any organ system fulfilling the criteria of chronic GVHD

National Marrow Donor Program

Center for International Blood and Marrow Transplant Research

Chronic Graft Versus Host Disease

Margaret F Bevans, Ph.D.

Background:

- Stem cell transplants are a complex treatment that can have serious side effects. Having a caregiver to help with the recovery is critical. Serving in this role, however, can cause high stress levels and negative health effects. Researchers want to better understand the health effects of caring for a family member or friend after a stem cell transplant. Understanding these effects can help develop programs that support caregivers coping with the demands of post-transplant care.

Objectives:

- To study the physical and emotional health of caregivers for a family member or friend who has had a stem cell transplant.

Eligibility:

* Individuals at least 18 years of age who are planning to be a caregiver for a person having a stem cell transplant.
* Healthy non-caregiver volunteers for comparison studies.

Design:

* A caregiver will be caring for a transplant recipient just before transplant admission and up through 6 weeks after hospital discharge. The caregiver will usually live with or spend at least 6 hours each day with the recipient.
* All participants will have three study visits. The first visit will happen before the transplant. The second and third visits will happen at the recipient s discharge, and 6 weeks after discharge. The following tests will be done at each visit:
* A health assessment with a physical exam and review of life events and current health problems
* Blood, hair, and saliva samples
* Questionnaires about stress levels, personal health, and the caregiving process.
* Caregiver participants may have an optional fourth study visit within 72 hours after an ICU admission. This visit will include the same tests as the other visits....

There are approximately 65.7 million unpaid caregivers in the United States with an estimated 8 percent providing care to someone with cancer. Although benefit-finding has been reported, providing care to a spouse or loved one with cancer is stressful and can have negative consequences for an individual s psychological and physical health. In cancer caregivers, studies have documented negative outcomes including symptoms of fatigue, impaired sleep quality, poor quality of life, anxiety and depression. These outcomes are of particular concern when cancer patients receive intense treatment such as hematopoietic stem cell transplantation (HSCT) where caregivers are embedded in a treatment trajectory that can extend 4 12 months. In dementia caregivers, additional outcomes have been reported including poor health habits and impaired immunity. In addition, longitudinal studies have also reported caregivers have an increased risk of morbidity and mortality, particularly from cardiovascular disease.

The stress response is initiated in the brain, which determines both the physiological and behavioral responses to an event. The normal physiologic response is complex and dynamic process by which the body responds to daily events in an effort to maintain equilibrium. If the stress becomes overwhelming for the individual, either due to the number or magnitude of stressors, the burden or overload can lead to dysregulation of biologic mediators and behavioral changes (poor sleep, eating or drinking too much, smoking, lack of physical activity) that can exacerbate disease (e.g. cardiovascular disease). A recent study in cancer caregivers demonstrated marked changes in neurohormonal and inflammatory processes in the year following a loved one s cancer diagnosis which may place the caregiver at risk for morbidity and mortality from disease. The relationships among the physiologic and psychological responses as well as behavioral changes to stress have not been explored in HSCT caregivers.

What is clear from the literature is that caregiving is stressful, and it appears to increase one s risk for morbidity and mortality, particularly by increasing cardiovascular risk. What is less clear is what behavioral, psychological, physiological and clinical changes are associated with the process of caregiver for individuals undergoing allogeneic HSCT, a particularly long and stressful experience. The purpose of this exploratory, pilot study is threefold: to longitudinally examine physiological, behavioral and clinical factors in HSCT caregivers during the acute transplant recovery period, to compare those factors in HSCT caregivers to non-caregivers, and to explore the associations among physiological, psychological, behavioral and clinical factors in HSCT caregivers.

Subjects will be accrued to this protocol if they are adult caregivers for a transplant recipient participating in their first allogeneic HSCT protocol at the Clinical Center. An equal sample of healthy volunteers that are non-caregivers will be recruited to serve as control subjects. A sample of 40 subjects (20 caregiver and 20 non-caregiver volunteers) will be recruited to capture the essence of the experience and adequately explore this population.

Each caregiver participant will have data collected prior to the recipient s HSCT (day 0), during the first week of outpatient visits following the recipient s initial discharge from the inpatient setting, and finally 6 weeks post the transplant recipients initial discharge from the hospital. Questionnaires will capture the psychological and behavioral outcomes and include: Caregiver Reaction Assessment (caregivers only), Health-Promoting Lifestyle Profile II, Perceived Stress Scale, The UCLA Loneliness Scale (Version 3), General Self-Efficacy Scale, and PROMIS Short Forms for Anxiety, Depression, Sleep disturbance and Fatigue. Clinical variables (e.g. vital signs) and physiological variables (e.g. cortisol) will be collected along with the questionnaires during the clinic visit and following history and physical exam by a Licensed Independent Practitioner (LIP). A sample of non-caregivers will be minimally matched for age, gender, and race/ethnicity, and complete all study procedures except the questionnaires that are specific to the caregiver s experience (e.g. caregiver burden). There will be no long term follow-up after the study participation period. Exploratory, hypothesis generating analyses will be performed using parametric and non-parametric techniques.

Physical and Emotional Health of Caregivers for People Who Have Had Stem Cell Transplants

A Pilot Study to Examine Physiological and Clinical Markers of Chronic Stress in Caregivers of Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Recipients

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Naive T-Cell Depleted DLI Following Allo Stem Cell Transplant	NCT01627275	Hematological M...	Naive T Cell De...	18 Years -	Duke University
Low-Intensity Stem Cell Transplantation With Multiple Lymphocyte Infusions to Treat Advanced Kidney Cancer	NCT00923845	Renal Cell Carc... Graft-Versus-Ho... Engraftment Syn...	Pentostatin Sirolimus Cyclophosphamid... Allogeneic Hema... Th2 rapa cells Donor Lymphocyt... Induction Thera... GVHD prophylaxi... Donor Hematopoi...	18 Years - 75 Years	National Institutes of Health Clinical Center (CC)
Naive T-Cell Depleted DLI Following Allo Stem Cell Transplant	NCT01627275	Hematological M...	Naive T Cell De...	18 Years -	Duke University
Assessment of Allogeneic Hematopoietic Cell Transplantation in Medicare Beneficiaries With Multiple Myeloma	NCT03127761	Multiple Myelom...	Allogeneic Hema...	-	Center for International Blood and Marrow Transplant Research
Naive T-Cell Depleted DLI Following Allo Stem Cell Transplant	NCT01627275	Hematological M...	Naive T Cell De...	18 Years -	Duke University
Physical and Emotional Health of Caregivers for People Who Have Had Stem Cell Transplants	NCT01468857	Stress Family Caregive...		18 Years -	National Institutes of Health Clinical Center (CC)
Assessment of Allogeneic Hematopoietic Cell Transplantation in Medicare Beneficiaries With Multiple Myeloma	NCT03127761	Multiple Myelom...	Allogeneic Hema...	-	Center for International Blood and Marrow Transplant Research
Oral Posaconazole Three Times Per Day vs Weekly High Dose Amphotericin B Lipid Complex (ABLC)	NCT00750737	Invasive Fungal... Hematologic Mal...	Posaconazole ABLC	18 Years -	M.D. Anderson Cancer Center
Cemiplimab in AlloSCT/SOT Recipients With CSCC	NCT04339062	Cutaneous Squam... Advanced Cancer	Cemiplimab Everolimus Sirolimus Prednisone	18 Years -	Dana-Farber Cancer Institute
Physical and Emotional Health of Caregivers for People Who Have Had Stem Cell Transplants	NCT01468857	Stress Family Caregive...		18 Years -	National Institutes of Health Clinical Center (CC)
Busulfan and Cyclophosphamide Followed By ALLO BMT	NCT01685411	Acute Lymphobla... Acute Myeloid L... Myelodysplastic...	Allopurinol Keppra Busulfan Cyclophosphamid... Tacrolimus Mycophenolate m... Allogeneic hema... Filgrastim antithymocyte g...	- 44 Years	Masonic Cancer Center, University of Minnesota

Spots Global Cancer Trial Database for allogeneic hematopoietic stem cell transplant