Microtransplantation Can Be Safe and Effective For Older AML Patients

MedicalResearch.com Interview with:
Huisheng Ai, MD, Director

Department of Hematology and Transplantation,
Affiliated Hospital of the Academy  of Military Medical Sciences,
Beijing, China 

MedicalResearch.com: Which of these results did you find most interesting or surprising?

Response: First, we must stress that microtransplant dramatically improved the outcome of older patients with AML.

As we know, older AML patients often possess unfavorable prognostic factors, organ dysfunction, and slow post-chemotherapy hematopoietic recovery. Therefore, the general treatment outcome is unsatisfactory even though the incidence is increasing by age with low complete remission (CR) rates (34% to 65%) and poor short-term survival (Two years overall survival was about 11% to 25%).

This study involved cases from multiple centers of China, USA and Spain, and found that microtransplant could not only significantly improve complete remission rate in older AML patients among all age groups from 60 to 85, but also improve 1-year and 2-year overall survival and disease free survival especially in patients aged 60 to 75. Second, microtransplant completely overcomes the restriction of HLA typing. The donor could be the patient’s haploidentical family member, or unrelated and fully mismatched one. The incidence of graft-versus-host disease (GVHD) was only 1.1%, even if no any GVHD prevention was given. Other treatment related complications and mortality were also decreased.

These results are much better than those of traditional chemotherapy, myeloablative and non-myeloablative transplant, which provides a more safe and effective treatment choice. We are looking forward to seeing the revision of NCCN guideline for older AML to make microtransplant benefit more older patients.

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Deceased Donor Kidneys Offered Median of 7 Times Before Acceptance For Transplant

MedicalResearch.com Interview with:

Dr. Anne Huml MD Center for Reducing Health Disparities Case Western Reserve University MetroHealth Medical Center Cleveland, Ohio

Dr. Huml

Dr. Anne Huml MD
Center for Reducing Health Disparities
Case Western Reserve University
MetroHealth Medical Center
Cleveland, Ohio 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Overall, about 600,000 Americans have end stage renal disease and require chronic dialysis treatment or a kidney transplant to survive. Compared to chronic dialysis, kidney transplantation results in better survival and quality of life and lower health care costs. Approximately 100,000 patients are listed for a kidney transplant. However, only 17,000 transplants occur per year with two-thirds of these coming from deceased donor organs. Annually, over 8,000 patients either die waiting for a kidney transplant or are removed from the waiting list for being too ill. Waiting times vary based on geography, but it is not unusual for patients to wait upwards of 5 years for a kidney transplant. There are sizeable race, gender, and socioeconomic disparities in access to kidney transplantation.

In this study, we evaluated the outcomes of deceased donor kidney offers and their association with donor and waitlisted patient characteristics. Differences in kidney offer outcomes to patients at the top of the waiting list may contribute to disparities in transplantation.

When a deceased donor organ becomes available, a match run list is created that ranks potential recipients in priority order based upon several characteristics, including waiting time and immunologic criteria. At the discretion of the transplant center, organ offers to patients on their waiting list can be accepted for transplant, or refused for a particular patient. The offers continue down the match run list in sequential order. For each potential recipient in whom the organ is not transplanted, a refusal code is generated and catalogued with the United Network of Organ Sharing, or UNOS. UNOS identifies 37 unique refusal codes and categorizes them into donor-related, transplant center bypassed for pre-specified criteria, recipient-related, histocompatibility-related, program-related, or other reasons for refusal.

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IgG Endopeptidase Has Potential To Reduce Kidney Transplant Rejection

MedicalResearch.com Interview with:

Stanley C. Jordan, M.D Director, Division of Nephrology Medical Director, Kidney Transplant Program Medical Director, Human Leukocyte Antigen and Transplant Immunology Laboratory Cedars-Sinai, Los Angeles, CA

Dr. Jordan

Stanley C. Jordan, M.D
DirectorDivision of Nephrology
Medical DirectorKidney Transplant Program
Medical Director, Human Leukocyte Antigen and Transplant Immunology Laboratory
Cedars-Sinai, Los Angeles, CA 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The background for this study is as follows: Patients who are highly HLA sensitized have antibodies to transplant targets create an immunologic barrier to transplant. Currently, there are no approved therapies for elimination of these antibodies. Desensitization is available but is not always successful and most desensitized patients are still transplanted with a positive crossmatch. Thus, many patients are not able to receive life-saving kidney transplants unless newer therapies to remove antibodies are found.

The findings of our study published in the New England Journal of Medicine revealed that the use of the enzyme from streptococcal pyogenes called IdeS® (IgG endopeptidase) is very effective in eliminating donor specific antibodies and allowing transplantation to occur. Antibodies were eliminated from one week up to two months after one treatment with Ides® allowing a safe environment for the transplant to occur. Rejections episodes did occur in some of the patients but were generally mild and easily treatable. Only one patient of 25 lost his allograft during the study. Thus, the study shows promising results for a new approach for elimination of pathogenic antibodies that did not exist before.

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Factors Affecting Interest in Transplant Among ESRD Patients Receiving Dialysis

MedicalResearch.com Interview with:

Deborah Evans, MA, MSW, LCSW Manager, Social Work Services DaVita Kidney Care

Deborah Evans

Deborah Evans, MA, MSW, LCSW
Manager, Social Work Services
DaVita Kidney Care

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: For patients with end-stage renal disease (ESRD) receiving dialysis, receipt of a transplant offers the best possible long-term treatment option. However, the process of becoming qualified to receive a transplant involves many steps, beginning with the patient’s statement of interest.

In this study, we sought to characterize transplant interest among patients in a large dialysis organization in the U.S. and to explore reasons identified by the patients for lack of interest in transplant when applicable.

As of November 2016, of the 182,906 patients with available transplant status information in the LDO database, 58,057 (31.7%) expressed that they were not interested in transplant. Among patients not interested in transplant, the most frequently identified reasons for lack of interest were:

  • Advanced age (25.7%)
  • Perceived poor health (12.0%)
  • Comfortable with current modality (12.0%)
  • Uninterested in further surgeries (11.9%)
  • 13.2% of patients not interested in transplant indicated that “other” factors were responsible for their lack of interest. At the time of the study, we didn’t have any further insight into what might account for these “other” factors.

Compared to patients with transplant status listed as active, those not interested in transplant were:

  • Older (21.4% < 60 years vs 64.6%)
  • More likely to be female (47.7% vs 36.6%)
  • More likely to be white (43.9% vs 30.4%) and less likely to be Hispanic (14.7% vs 22.2%)
  • More likely to be receiving in-center hemodialysis (92.0% vs 73.7%)
  • More likely to have Medicare/Medicaid as primary insurance (91.3% vs. 77.3%)

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Food Costs Can Lead To Less Protein and Phosphorous in Indigent Kidney Transplant Patients

MedicalResearch.com Interview with:

Ms. Shifra Mincer Medical Student in the class of 2019 SUNY Downstate Medical School

Shifra Mincer

Ms. Shifra Mincer
Medical Student in the class of 2019
SUNY Downstate Medical School

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Hypophosphatemia is commonly encountered in the post-transplant setting. Early post-transplant hypophosphatemia has been ascribed to excess FGF23 and hyperphosphaturia.

Many patients remain hypohosphatemic months or even years after their transplant and the mechanism was assumed to be the same, however, our group recently reported that patients with late post-transplant hypophosphatemia had very little phosphorous in their urine (Wu S, Brar A, Markell, MS. Am J Kidney Dis. 2016,67(5): A18). We hypothesized that they were not eating enough phosphorous to compensate for the acute phosphorous losses they experienced immediately post-transplant.

In this study, using both 3-day diet journals and 24-hour diet recall questionnaires, we found that mean intake of phosphorous and protein was barely at the Recommended Daily Allowance, and that despite 70% of the patients using EBT, 30% of those patients still reported concerns regarding food security. Patients who reported that the cost of food influenced their dietary choices ate 43% less protein (average 48,5 gms vs. 85.8 gms) and 29% less phosphorous (average 887 mg vs 1257 mg). When ability to rise from a chair over a 30 second period was evaluated, only patients who expressed food cost concerns were unable to complete the test.

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Fecal Transplantation Reduced Hospitalizations and Improved Cognitive Function in Cirrhosis Trial

MedicalResearch.com Interview with:

Jasmohan S. Bajaj, M.D. Virginia Commonwealth University Associate Professor Department of Internal Medicine Division of Gastroenterology

Dr. Bajaj

Jasmohan S. Bajaj, M.D.
Virginia Commonwealth University
Associate Professor
Department of Internal Medicine
Division of Gastroenterology

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Hepatic encephalopathy is a devastating complication of cirrhosis, which often recurs despite standard of care therapy with lactulose and rifaximin. This has a basis in an altered gut milieu therefore we need to change that in a more meaningful way to help patients. This was an FDA-monitored Phase I safety study of Fecal microbiome transfer (FMT) using a rationally-derived donor compared to standard of care.

We found that FMT was safe and was associated with lower all-cause and hepatic encephalopathy-related hospitalizations over 5 months compared to standard of care.

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Donor Sex and Size Important to Kidney Transplant Success

MedicalResearch.com Interview with:
Amanda Miller, MD, FRCPC

Dalhousie University
Transplant Nephrology

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Earlier studies have shown that there may be a higher risk of kidney transplant failure if a kidney donor is smaller than their recipient. This may be due to increased strain on the relatively smaller transplanted kidney. Very few studies have investigated outcomes associated with donor and recipient weight mismatch measured directly by differences in body weight however. There is also a suggestion that sex mismatch between kidney donor and recipient may lead to worse outcomes post-transplant, however results from earlier studies have been controversial and conflicting. The combined effect of weight and sex matching/mismatching between kidney donor and recipient (two very important and physiologically relevant factors) has not been rigorously studied previously.

Thus, the aim of this study was to determine if receiving a kidney transplant from a smaller donor of the opposite sex would impact transplant outcomes. Accounting for other transplant variables, we demonstrated that if a kidney transplant recipient is more than 30 kg (66 pounds) heavier than the donor there is a 28% increased risk of the transplant failing compared to equally weighted donors and recipients. If the kidney is from a smaller donor of the opposite sex, the risk of transplant failure is further increased to 35% for a male receiving a kidney from a female donor, and 50% for a female receiving a kidney from a male donor. This risk is high and is similar to that when a recipient receives a kidney transplant from a donor who has diabetes; a known risk factor for kidney failure in the non-transplant population.

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Frozen Fecal Transplant in Pill Form Found To Reverse C. Diff Infection

MedicalResearch.com Interview with:

Dr. H. L. DuPont MD Director, Center for Infectious Diseases, UTHealth School of Public Health Mary W. Kelsey Chair in the Medical Sciences, McGovern Medical School at UTHealth Professor, Department of Epidemiology, Human Genetics and Environmental Sciences UTHealth School of Public Health Houston, TX 77030

Dr. DuPont

Dr. H. L. DuPont MD
Director, Center for Infectious Diseases, UTHealth School of Public Health
Mary W. Kelsey Chair in the Medical Sciences, McGovern Medical School at UTHealth
Professor, Department of Epidemiology, Human Genetics and Environmental Sciences
UTHealth School of Public Health
Houston, TX 77030

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Many diseases and disorders are associated with “dysbiosis,” where the intestinal microbiota diversity is reduced. This contributes to disease and to the acquisition of antibiotic resistance. Fecal microbiota transplantation (FMT) is successful in conditions with pure dysbiosis (e.g. C diff infection) and a single dose of FMT is curative in most cases.

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Comparison of Posttransplant Dermatologic Diseases by Race

MedicalResearch.com Interview with:
Christina Lee Chung, MD, FAAD
Associate Professor of Dermatology
Director, Center for Transplant Patients
Drexel University College of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It’s long been recognized immunosuppressed organ transplant recipients are at significantly increased risk for skin cancer and other types of skin disease.

But despite advances to improve skin cancer prevention for these patients, little is known about how skin conditions affect African-American, Asian and Hispanic transplant recipients. This is problematic given that, according to the U.S. Department of Health and Human Services, more than half of the 120,000 Americans on the waiting list for organs identify as nonwhite.

We compared medical records of 412 organ transplant recipients — including 154 white patients and 258 nonwhite (black, Asian or Hispanic) — who were referred to the Drexel Dermatology Center for Transplant Patients between 2011 and 2016. As one of the only models of its kind in the country, the center provides post-transplant dermatological care to every patient who is transplanted by and/or followed by the Drexel University and Hahnemann University Hospital Transplant Programs. That means that every patient, regardless of race, is screened annually for skin cancer, which provided a unique dataset for us to analyze.

Two hundred eighty-nine transplant recipients exhibited malignant, infectious or inflammatory conditions during their evaluation, but their primary acute diagnoses differed greatly by race. In 82 white patients, skin cancer was the most common acute problem requiring attention at first visit. Black and Hispanic patients, by contrast, were most often diagnosed with inflammatory or infectious processes, such as fungal infections, warts, eczema, psoriasis, and rashes that required immediate medical attention.

Overall, squamous cell carcinoma in situ was the most common type of skin cancer diagnosed in each racial or ethnic group. But the location of the cancerous lesions again depended on the race of the patient. Most lesions in white and Asian patients occurred in sun-exposed areas of the body, like the scalp, neck, chest and back. For black patients, the lesions were primarily found in the groin.  Moreover, six of the nine lesions found on black patients tested positive for high-risk HPV strains, suggesting an association between the virus and skin cancer for African Americans.

We also provided questionnaires to 66 organ transplant recipients to find out more about the patients’ awareness of skin cancer prevention. Seventy-seven percent of white patients were aware their skin cancer risk was increased, compared to 68 percent of nonwhites. Only 11 percent of nonwhite patients reported having regular dermatologic examinations, compared to 36 percent of whites. Finally, 45 percent of white patients but only 25 percent of nonwhite reported knowing the signs of skin cancer.

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Cancer Killed While Preserving A Kidney Transplant

MedicalResearch.com Interview with:

Kenar D. Jhaveri, MD Professor of Medicine Division of Kidney Diseases and Hypertension Hofstra Northwell School of Medicine, 100 Community Drive, Great Neck, NY 11021

Dr. Kenar Jhaveri,

Kenar D. Jhaveri, MD
Professor of Medicine
Division of Kidney Diseases and Hypertension
Hofstra Northwell School of Medicine,
100 Community Drive, Great Neck, NY 11021

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The immune check point inhibitors are novel anti cancer agents being used rapidly in various cancers. Many cancers don’t allow our natural immune system to attack the cancer. These immunotherapy agents “activate” the immune system to attack the cancer. These agents have been reported to cause multiple end organ side effects as noted by this recent NYT article. We also recently reported the known renal effects of immunotherapy.

In the kidney transplant patient who is on immunosuppressive agents, the physicians need to keep the immune system suppressed to preserve the kidney. When one of these agents are used for a cancer in a kidney transplant patient, prior reports have suggested severe rejection episodes and loss of the transplanted kidney. Our case in the NEJM is the first report of a preventive strategy used to allow for simultaneous treatment of cancer and preventive rejection of the kidney. We used a regimen of steroids and sirolimus( an anti-proliferative agent that is used to treat cancer and also is an immunosuppresant) along with the immunotherapy. The cancer started regressing and the kidney did not reject.

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