Chadalavada D.,Beckman Research Institute |
Burnett J.C.,Beckman Research Institute |
Chen R.W.,Hematology and Hematopoietic Cell Transplantation |
Rossi J.J.,Beckman Research Institute
Comparative Medicine | Year: 2014
NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice are a superior strain for the engraftment of human tumors, as they provide an ideal model to explore the potency, toxicity, and dosage of therapeutic drugs. Although whole-body nonlethal irradiation is often performed to enhance engraftment, the need for irradiation to establish a human B-cell lymphoma model using the NSG strain has not been addressed. In the current study, a mouse model of B-cell lymphoma was established by intravenous injection of human B-cell lymphoma Z138 cells into mice with and without irradiation. Tumor development, signs of engraftment, survivability of engrafted mice, histopathology, and immunohistochemistry were evaluated. Potential sex-associated variations in the model were assessed also. Irradiation of NSG mice did not enhance tumor cell engraftment, and nonirradiated animals had increased survivability. Mice with irradiation survived for a median of 27 d before being euthanized due to signs of morbidity, whereas those without irradiation had a median survival of 35 d. Both irradiated and nonirradiated mice were normal in activity until 3 wk after the injection of cells. At that time, the mice started to show signs of lymphoma including ruffled fur, decreased activity, and hindlimb paralysis. There were no significant differences in evaluated parameters between male and female mice. Therefore, we conclude that a model of B-cell lymphoma can successfully be established by using Z138 cells in nonirradiated male and female NSG mice. Copyright 2014 by the American Association for Laboratory Animal Science.
PubMed | Hematology and Hematopoietic Cell Transplantation and Beckman Research Institute
Type: Comparative Study | Journal: Comparative medicine | Year: 2014
NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) mice are a superior strain for the engraftment of human tumors, as they provide an ideal model to explore the potency, toxicity, and dosage of therapeutic drugs. Although whole-body nonlethal irradiation is often performed to enhance engraftment, the need for irradiation to establish a human B-cell lymphoma model using the NSG strain has not been addressed. In the current study, a mouse model of B-cell lymphoma was established by intravenous injection of human B-cell lymphoma Z138 cells into mice with and without irradiation. Tumor development, signs of engraftment, survivability of engrafted mice, histopathology, and immunohistochemistry were evaluated. Potential sex-associated variations in the model were assessed also. Irradiation of NSG mice did not enhance tumor cell engraftment, and nonirradiated animals had increased survivability. Mice with irradiation survived for a median of 27 d before being euthanized due to signs of morbidity, whereas those without irradiation had a median survival of 35 d. Both irradiated and nonirradiated mice were normal in activity until 3 wk after the injection of cells. At that time, the mice started to show signs of lymphoma including ruffled fur, decreased activity, and hindlimb paralysis. There were no significant differences in evaluated parameters between male and female mice. Therefore, we conclude that a model of B-cell lymphoma can successfully be established by using Z138 cells in nonirradiated male and female NSG mice.
Kumar S.K.,Mayo Medical School |
Flinn I.,Sarah Cannon Research Institute |
Noga S.J.,Sinai Hospital of Baltimore |
Hari P.,Medical College of Wisconsin |
And 13 more authors.
Leukemia | Year: 2010
This phase 1 study (Clinicaltrials.gov: NCT00507442) was conducted to determine the maximum tolerated dose (MTD) of cyclophosphamide in combination with bortezomib, dexamethasone and lenalidomide (VDCR) and to assess the safety and efficacy of this combination in untreated multiple myeloma patients. Cohorts of three to six patients received a cyclophosphamide dosage of 100, 200, 300, 400 or 500 mg/m 2 (on days 1 and 8) plus bortezomib 1.3 mg/m 2 (on days 1, 4, 8 and 11), dexamethasone 40 mg (on days 1, 8 and 15) and lenalidomide 15 mg (on days 1-14), for eight 21-day induction cycles, followed by four 42-day maintenance cycles (bortezomib 1.3 mg/m 2, on days 1, 8, 15 and 22). The MTD was the cyclophosphamide dose below which more than one of six patients experienced a dose-limiting toxicity (DLT). Twenty-five patients were treated. Two DLTs were seen, of grade 4 febrile neutropenia (cyclophosphamide 400 mg/m 2) and grade 4 herpes zoster despite anti-viral prophylaxis (cyclophosphamide 500 mg/m 2). No cumulative hematological toxicity or thromboembolic episodes were reported. The overall response rate was 96%, including 20% stringent complete response (CR), 40% CR/near-complete response and 68% very good partial response. VDCR is well tolerated and highly active in this population. No MTD was reached; the recommended phase 2 cyclophosphamide dose in VDCR is 500 mg/m 2, which was the highest dose tested. © 2010 Macmillan Publishers Limited All rights reserved.
News Article | December 6, 2016
DUARTE, Calif.--(BUSINESS WIRE)--For the 45th year, City of Hope will be participating in the 128th annual Tournament of Roses Parade celebrating the past, present and future successes of City of Hope’s physicians, researchers, scientists, nurses and survivors. By fostering collaboration between scientists and physicians, City of Hope is able to speed scientific advances to patients, enabling them to live successful, rewarding lives after cancer. No one knows that better than the seven patients riding atop this year’s float, a group that includes a kidney cancer survivor who has gone on to serve as president of the State Bar of California, another who left the grape fields to become a nurse and a former pediatric patient who is on his way to becoming a pediatric oncologist. The theme for the 128th annual Rose Parade is "Echoes of Success." City of Hope’s float, themed “The Miracle of Science with Soul,” reflects the comprehensive cancer center’s unique offering, a combination of leading-edge research and lifesaving, patient-centered care. This combination has created countless second chances for patients suffering from cancer, diabetes and other life-threatening diseases. Patients credit their medical teams with giving them those second chances and an opportunity to lead rich, selfless lives. The seven patients riding the float will be celebrating each other’s successes that were made possible through the selfless contributions of others. Riding and walking alongside the float are some of the doctors, nurses and caregivers who played a role in the patients’ healing. Commander Anne Clark: As the Los Angeles Police Department’s first female Hispanic commander, Anne Clark takes nothing for granted. She has spent the past 30 years with the law enforcement agency and has had her share of life-threatening moments over the years, but none hitting closer to home than her cancer Hodgkin lymphoma diagnosis two years ago. Clark resolved to beat the disease with the support of dozens of police officers rallying around her during her fight. Today she is in remission and is thankful to her medical team and fellow officers for helping her through one of the most challenging times of her life. Clark will be riding alongside her hematologist/oncologist, Stephen J. Forman, M.D., the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation at City of Hope. Darrell George: The current city manager for Duarte, Darrell George, cannot recall a time when he was sick. He cannot even remember a time he had a cold. So when he went in for an annual physical he was surprised to learn that he had developed a mass that was diagnosed as non-Hodgkin lymphoma. George immediately traveled to City of Hope and now, nearly two years later, he is in remission. He will also ride with Forman, his hematologist/oncologist. Dave Pasternak: As a successful Los Angeles attorney, cancer was the last thing Dave Pasternak had on his mind when he began experiencing a lingering case of bronchitis in 2014. That case of bronchitis, however, turned out to be advanced kidney cancer that had already begun to spread to other organs. Given the extent of his cancer, some estimated Pasternak's survival at between six months and a year — maybe even less. That’s when Pasternak came to City of Hope, where he enrolled in a clinical trial to help treat his cancer. Pasternak has been responding well. So well, in fact, that while recovering from treatment, he has successfully gone on to become the 91st president of the State Bar of California. Pasternak will be riding alongside his oncologist, Sumanta K. Pal, M.D., assistant clinical professor in the Department of Medical Oncology & Therapeutics Research. Jackie Garcia: Jackie Garcia was only 10 years old when she had to half her jaw removed due to Ewing’s sarcoma, an aggressive bone cancer that mainly strikes children and adolescents and accounts for about 1 percent of childhood cancers. To avoid facial scars, City of Hope surgeons removed the tumor by making an incision in Garcia’s neck and rebuilt her jaw using a portion of her fibula, along with small blood vessels. The complex surgery was successful and now Garcia, 14, has her sights set on becoming a surgeon herself when she grows up. “I want to be able to share some of the love and comfort that my doctors gave me on so many occasions.” Garcia will be riding alongside her surgeons, Ellie Maghami, M.D., Chief of Otolaryngology/Head and Neck Surgery, and Robert Kang, M.D., M.P.H., assistant clinical professor in the Division of Otolaryngology/Head & Neck Surgery. Rodrigo Nunez: When Rodrigo Nunez was 18 years old, he thought he was destined to be a field worker. He spent his days picking grapes until one day he started to get sick. Soon, he was diagnosed with a rare, potentially fatal blood disease called aplastic anemia. His experience with a life-threatening illness, ironically, gave him the clearest glimpse of his future. During treatment at City of Hope he decided he would go back to school and become a nurse. Weeks after graduating, Nunez’ story came full circle: He was hired as a nurse at City of Hope. He cared for one of his first patients — coincidentally, a young man with aplastic anemia — in the same hospital room where he was treated. “Talk about a dream come true,” says Nunez, now 56. “I was taking care of patients, working with the same doctors and nurses who saved my life.” Sebastian Sanchez-Luege: Sebastian Sanchez-Luege was just 6 years old when he was diagnosed with non-Hodgkin anaplastic large cell lymphoma, a rare condition that accounts for just 2 percent of blood cancers. A year later, just two weeks after he turned 7, Sanchez-Luege underwent a lifesaving stem cell transplant. While the road to recovery wasn’t easy, Sanchez-Luege has “no doubt” that the experience positively impacted his life and the people around him. Now a senior at Stanford University, Sanchez-Luege is preparing to graduate this June. His goal: to attend medical school and become a doctor. “I want to help other patients face their illnesses with hope and empathy, knowing full well what it is like to be a patient.“ Linh Quan: Diagnosed with breast cancer after a routine mammogram at 40 years old, Quan traveled to City of Hope, where she knew from experience that she would be in good hands. After intense rounds of chemotherapy, Quan underwent a double mastectomy and spent another six months undergoing follow-up chemotherapy. Four years later, she is now cancer-free and focused on giving back as a result of the specialized care she received. “I feel very honored, and I hope to do whatever I can to make a difference.” Quan will be riding alongside her oncologist, Christina Yeon, M.D. City of Hope is an independent research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as one of only 47 comprehensive cancer centers, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the world. City of Hope is located in Duarte, California, just northeast of Los Angeles, with community clinics throughout Southern California. It is ranked as one of "America's Best Hospitals" in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation, diabetes and numerous breakthrough cancer drugs based on technology developed at the institution. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.
News Article | December 3, 2016
DUARTE, Calif.--(BUSINESS WIRE)--Clinical trials that lay the groundwork for novel lymphoma, leukemia and multiple myeloma treatments will be among the highlights of the annual meeting of the American Society of Hematology (ASH) in San Diego Dec. 3 to 6. The trials, presented by City of Hope physicians and researchers, could ultimately lead to innovative therapeutic approaches that improve survival and quality of life for patients with those and other diseases. The ASH meeting, which will host more than 20,000 investigators working on blood diseases, including cancers, encourages clinicians and scientists working both ends of the bench-to-bedside translational research spectrum to discuss the latest results in marathon talks and poster sessions, often sharing the latest available research. “The ASH meeting brings together the best and brightest physicians and researchers in hematology to discuss the most promising research and treatment in the field,” said Stephen J. Forman, M.D., leader of City of Hope’s Hematologic Malignancies and Stem Cell Transplantation Institute and the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation. “Patients around the world ultimately benefit from leading-edge research presented at ASH.” Among the research presented by City of Hope scientists will be results of four clinical trials that lay the groundwork for novel leukemia, lymphoma or multiple myeloma treatments. Those studies address: Combination therapy results for patients with relapsed or refractory Hodgkin lymphoma. While many patients with Hodgkin lymphoma are cured with initial chemotherapy, challenges remain for treating patients who face relapsed or treatment-resistant disease. Alex Herrera, M.D., assistant professor in City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation and a hematologist/oncologist, led a phase 1/2 study of 42 participants that tested the safety and antitumor activity of brentuximab vedotin — an antibody-drug conjugate that induces an anti-tumor immune response — combined with nivolumab for use in people with relapsed or treatment-resistant Hodgkin lymphoma. Nivolumab is an immunotherapy that can restore anti-tumor immune responses by blocking the PD-1 immune checkpoint pathway, which tumors hijack to evade the immune system. Since both agents have shown success when used independently to treat the disease, researchers believed a combination approach could improve complete response rates prior to a stem cell transplant, as well as long-term outcomes. Herrera and his team found that the drug combination is a well-tolerated therapy for patients with relapsed or treatment-resistant Hodgkin lymphoma who have failed standard frontline chemotherapy. (Patients initially could have had treatment-resistant disease, or relapsed after entering a remission.) Study results also suggest that the anti-tumor activity of this combination therapy may be a promising option for this patient population. Herrera will share additional results at his ASH oral presentation on Monday, Dec. 5, at 10:45 a.m. Novel therapy for acute myeloid leukemia. For newly diagnosed acute myeloid leukemia (AML) patients under the age of 65, standard treatment is induction chemotherapy, or high doses of drugs at a continuous rate in order to kill as many cancer cells as fast as possible. While the standard combination of infused cytarabine for seven days plus anthracycline for three days (what’s known as 7+3 chemotherapy) results in a high complete response rate, a significant number of patients either experience treatment resistance or evidence of minimal residual disease. This is why a group of researchers is seeking ways to enhance and deepen remissions for AML patients. A phase 1b study involving Anthony Stein, M.D., director of the Leukemia Program and co-director of the Gehr Family Center for Leukemia Research at City of Hope, and other researchers from across the country evaluated the safety and anti-leukemic activity of a therapy that added Vadastuximab Talirine (33A) to 7+3 chemotherapy. 33A is an antibody and drug combination that targets CD33, an antigen expressed by approximately 90 percent of AML patients. The drug delivered by 33A, a pyrrolobenzodiazepine dimer, is a more powerful killer of cancer cells than systemic chemotherapeutic drugs and is released directly into CD33-expressing cells. Results from the study, which will be discussed at an ASH press briefing on Saturday, Dec. 3, at noon, included 42 patients that have shown that 33A can be safely combined with 7+3 therapy when accompanying treatment on days 1 and 4. An alternate schedule of single-day dosing on the first day of treatment is under investigation. Adverse effects of the combination therapy and induction mortality rates were also similar to those reported using 7+3 alone in this AML population. A high remission rate was seen after one cycle of the treatment with the majority of those patients showing no signs of minimal residual disease. Clinical trial examines autologous stem cell transplants in multiple myeloma patients. Multiple myeloma patients who receive an autologous blood stem cell transplant must also take medication after the procedure to kill cancer cells. The largest randomized trial examining autologous transplants in multiple myeloma patients tested various drug combinations that patients took after the procedure. The study aimed to answer the question: What is the best option after a transplant to increase the length of remission? The phase 3 randomized study involving two City of Hope physicians – Amrita Krishnan, director of the Judy and Bernard Briskin Center for Multiple Myeloma Research and professor in the Department of Hematology & Hematopoietic Cell Transplantation, and George Somlo, professor in the Department of Medical Oncology & Therapeutics Research – involved 758 patients who first received a transplant and high dose melphalan, a chemotherapy drug. One group took an intense, short course of a combination of drugs known as “RVD,” or lenalidomide (R), an immunomodulatory agent, bortezomib (V), a proteasome inhibitor, and dexamethasone (D), a steroid that can augment the effects of those two drugs, followed by lenalidomide maintenance, a course of therapy aimed at keeping a patient in remission. A second group took just lenalidomide as a maintenance, and a third group underwent a second transplant followed by lenalidomide maintenance. Multiple myeloma in 57 percent of the patients had not progressed after a 38-month period among patients who took the RVD consolidation and melphalan; similar results were seen in 56 percent of patients taking melphalan and lenalidomide, and 52 percent of patients taking lenalidomide. Overall survival for the three groups was 86, 82 and 83 percent, respectively. Researchers concluded that progression-free and overall survival rates were comparable in all three groups. Thus, adding intensive therapies after the initial transplant (and before lenalidomide maintenance) did not significantly impact the outcomes for patients. Study results will be discussed during an ASH late breaking abstracts session on Tuesday, Dec. 6, at 7:30 a.m. Long-term outcomes of ASCT in HIV-infected patients. A retrospective study of 50 HIV-positive patients who received autologous stem cell transplant for treatment of non-Hodgkin lymphoma at City of Hope was led by hematologist Liana Nikolaenko, M.D. The study, in which all of the transplantation and follow-up analysis was done at City of Hope, is the single largest institution study reporting on long-term outcomes for autologous stem cell transplant in HIV-positive patients with non-Hodgkin lymphoma. The analysis examined the long-term outcomes of people who received the transplant between January 1998 and December 2011. Prior to transplantation, 46 percent of patients — most of whom had aggressive non-Hodgkin lymphoma — were in complete remission, and 54 percent were in partial remission. At the time of analysis, 35 out of 50 patients (70 percent) were alive, confirming the efficacy of that transplant in this patient population. In addition, the City of Hope research team found that second primary malignancies and opportunistic infections, which can be associated with autologous stem cell transplant, particularly in patients with HIV, were not major factors in mortality for this cohort, and neither was HIV infection. Of the 15 patients (30 percent) that died, the cause of death was relapsed disease in eight patients (53 percent). Study results will be presented during an ASH presentation on Monday, Dec. 5, at 6 p.m. City of Hope is an independent research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as one of only 47 comprehensive cancer centers, the highest recognition bestowed by the National Cancer Institute, City of Hope is also a founding member of the National Comprehensive Cancer Network, with research and treatment protocols that advance care throughout the world. City of Hope is located in Duarte, California, just northeast of Los Angeles, with community clinics throughout Southern California. It is ranked as one of "America's Best Hospitals" in cancer by U.S. News & World Report. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation, diabetes and numerous breakthrough cancer drugs based on technology developed at the institution. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.
News Article | December 7, 2016
SEATTLE--(BUSINESS WIRE)--Omeros Corporation (NASDAQ: OMER) today announced that an abstract highlighting positive results from the ongoing OMS721 Phase 2 clinical trial in patients with hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) has been accepted for presentation at the 2017 Tandem Meeting of the American Society of Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research in Orlando, Florida. OMS721 is Omeros’ lead human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2). In addition to its Phase 2 clinical program in TMAs, OMS721 is currently in a Phase 3 program for patients suffering from atypical hemolytic uremic syndrome and in a Phase 2 program for renal diseases, including immunoglobulin A (IgA) nephropathy and membranous nephropathy. The title of the abstract is “Early Results of Phase II Study Using OMS721 in Patients with Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (HCT-TMA),” and will be presented on Saturday, February 25, by Dr. Samer Khaled, M.D., Assistant Clinical Professor of Hematology and Hematopoietic Cell Transplantation at City of Hope in Duarte California and OMS721 clinical investigator. Omeros controls the worldwide rights to MASP-2 and all therapeutics targeting MASP-2, a novel pro-inflammatory protein target involved in activation of the complement system, which is an important component of the immune system. The complement system plays a role in the inflammatory response and becomes activated as a result of tissue damage or microbial infection. MASP-2 is the effector enzyme of the lectin pathway, one of the principal complement activation pathways. Importantly, inhibition of MASP-2 does not appear to interfere with the antibody-dependent classical complement activation pathway, which is a critical component of the acquired immune response to infection, and its abnormal function is associated with a wide range of autoimmune disorders. MASP-2 is generated by the liver and is then released into circulation. Adult humans who are genetically deficient in one of the proteins that activate MASP-2 do not appear to be detrimentally affected by the deficiency. Omeros has received both Orphan Drug status and Fast Track designation from the U.S. FDA for its lead human MASP-2 antibody OMS721. Following discussions with both the FDA and the European Medicines Agency, a Phase 3 program for OMS721 in atypical hemolytic uremic syndrome is in progress. Also, two Phase 2 trials are ongoing. One is evaluating OMS721 in glomerulonephropathies, which has generated positive data in patients with immunoglobulin A (IgA) nephropathy and with membranous nephropathy and the other is being conducted in patients with thrombotic microangiopathies (TMAs), with positive data reported in patients with hematopoietic stem cell transplant-associated TMA. In addition to potential intravenous administration, Omeros plans to commercialize OMS721 for one or more therapeutic indications as a subcutaneous injection and is also developing small-molecule inhibitors of MASP-2. Based on requests from treating physicians, Omeros has established a compassionate-use program for OMS721, which is active in both the U.S. and Europe. Omeros also has identified MASP-3 as the protein that is critical to the activation of the complement system’s alternative pathway in humans, which is linked to a wide range of immune-related disorders. In addition to its lectin pathway inhibitors, the company is advancing its development of antibodies and small-molecule inhibitors against MASP-3 to block activation of the alternative pathway. Omeros is a biopharmaceutical company committed to discovering, developing and commercializing both small-molecule and protein therapeutics for large-market as well as orphan indications targeting inflammation, coagulopathies and disorders of the central nervous system. Part of its proprietary PharmacoSurgery® platform, the company’s first drug product, OMIDRIA® (phenylephrine and ketorolac injection) 1% / 0.3%, was broadly launched in the U.S. in April 2015. OMIDRIA is the first and only FDA-approved drug (1) for use during cataract surgery or intraocular lens (IOL) replacement to maintain pupil size by preventing intraoperative miosis (pupil constriction) and to reduce postoperative ocular pain and (2) that contains an NSAID for intraocular use. In the European Union, the European Commission has approved OMIDRIA for use in cataract surgery and lens replacement procedures to maintain mydriasis (pupil dilation), prevent miosis (pupil constriction), and to reduce postoperative eye pain. Omeros has clinical-stage development programs focused on: complement-associated thrombotic microangiopathies; complement-mediated glomerulonephropathies; Huntington’s disease and cognitive impairment; and addictive and compulsive disorders. In addition, Omeros has a proprietary G protein-coupled receptor (GPCR) platform, which is making available an unprecedented number of new GPCR drug targets and corresponding compounds to the pharmaceutical industry for drug development, and a platform used to generate antibodies. This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, which are subject to the “safe harbor” created by those sections for such statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “look forward to,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” and similar expressions and variations thereof. Forward-looking statements are based on management’s beliefs and assumptions and on information available to management only as of the date of this press release. Omeros’ actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, risks associated with product commercialization and commercial operations, unproven preclinical and clinical development activities, regulatory oversight, intellectual property claims, competitive developments, litigation, and the risks, uncertainties and other factors described under the heading “Risk Factors” in the company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 9, 2016. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and the company assumes no obligation to update these forward-looking statements, even if new information becomes available in the future.
Wong F.L.,Population science |
Francisco L.,Population science |
Togawa K.,Population science |
Kim H.,Population science |
And 7 more authors.
Blood | Year: 2013
This prospective study described the trajectory of sexual well-being from before hematopoietic cell transplantation (HCT) to 3 years after in 131 allogeneic and 146 autologous HCT recipients using Derogatis Interview for Sexual Function and Derogatis Global Sexual Satisfaction Index. Sixty-one percent of men and 37% of women were sexually active pre-HCT; the prevalence declined to 51%(P 5.01) in men and increased to 48% (P 5 .02) in women at 3 years post-HCT. After HCT, sexual satisfaction declined in both sexes (P < .001). All sexual function domains were worse in women compared with men (P ≤ .001). Orgasm (P 5 .002) and drive/relationship (P < .001) declined inmen, but sexual cognition/fantasy (P 5.01) and sexual behavior/ experience (P 5 .01) improved in women. Older age negatively impacted sexual function post-HCT in both sexes (P < .01). Chronic graft-versus-host disease was associated with lower sexual cognition/fantasy (P 5 .003) and orgasm (P 5 .006) in men and sexual arousal (P 5.05) and sexual satisfaction (P 5.005) in women. Allmale sexual function domains declined after total body irradiation (P < .05). This study identifies vulnerable subpopulations that could benefit from interventional strategies to improve sexual well-being. © 2013 by The American Society of Hematology.
Sun C.-L.,Population science |
Francisco L.,Population science |
Baker K.S.,Fred Hutchinson Cancer Research Center |
Weisdorf D.J.,University of Minnesota |
And 2 more authors.
Blood | Year: 2011
Little information exists regarding long-term psychological health of hematopoietic cell transplantation (HCT) survivors. Using resources offered by the Bone Marrow Transplant Survivor Study (BMTSS), we evaluated adverse psychological outcomes in 1065 long-term HCT survivors and a healthy comparison group composed of siblings. Psychological health status was evaluated using the Brief Symptom Inventory-18. Twenty-two percent of the HCT survivors reported adverse psychological outcomes, compared with 8% of the siblings. Exposure to prednisone was associated with psychological distress across all domains (anxiety, depression, and somatic distress). Fifteen percent of the HCT survivors reported somatic distress, representing an almost 3-fold higher risk comparing to siblings. Among survivors, in addition to low annual household income and self-reported poor health, having severe/life-threatening conditions and presence of active chronic GVHD were associated with a 2-fold increased risk for somatic distress. Seven percent of the HCT survivors expressed suicidal ideation; patients with higher scores on depression subscale were most vulnerable. This study demonstrates that somatic distress is the biggest challenge faced by survivors long after HCT. These results identify vulnerable subpopulations and provide patients, families, and healthcare providers with necessary information to plan for post-HCT needs many years after HCT. © 2011 by The American Society of Hematology.
Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: A report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS)
Armenian S.H.,Population science |
Sun C.-L.,Population science |
Kawashima T.,Fred Hutchinson Cancer Research Center |
Arora M.,University of Minnesota |
And 14 more authors.
Blood | Year: 2011
HSCT is being increasingly offered as a curative option for children with hematologic malignancies. Although survival has improved, the long-term morbidity ascribed to the HSCT procedure is not known. We compared the risk of chronic health conditions and adverse health among children with cancer treated with HSCT with survivors treated conventionally, as well as with sibling controls. HSCT survivors were drawn from BMTSS (N = 145), whereas conventionally treated survivors (N = 7207) and siblings (N = 4020) were drawn from CCSS. Self-reported chronic conditions were graded with CTCAEv3.0. Fifty-nine percent of HSCT survivors reported ≥ 2 conditions, and 25.5% reported severe/life-threatening conditions. HSCT survivors were more likely than sibling controls to have severe/life-threatening (relative risk [RR] = 8.1, P < .01) and 2 or more (RR = 5.7, P < .01) conditions, as well as functional impairment (RR = 7.7, P < .01) and activity limitation (RR = 6.3, P < .01). More importantly, compared with CCSS survivors, BMTSS survivors demonstrated significantly elevated risks (severe/life-threatening conditions: RR = 3.9, P < .01; multiple conditions: RR = 2.6, P < .01; functional impairment: RR = 3.5, P < .01; activity limitation: RR = 5.8, P < .01). Unrelated donor HSCT recipients were at greatest risk. Childhood HSCT survivors carry a significantly greater burden of morbidity not only compared with noncancer populations but also compared with conventionally treated cancer patients, providing evidence for close monitoring of this high-risk population. © 2011 by The American Society of Hematology.