Unrelated Donor Cord Blood Transplantation in Children: Lessons Learned Over 3 Decades.

Four decades ago, Broxmeyer et al. demonstrated that umbilical cord blood (CB) contained hematopoietic stem cells (HSC) and hypothesized that CB could be used as a source of donor HSC for rescue of myeloablated bone marrow. In 1988, Gluckman et al. reported the first successful matched sibling cord blood transplant (CBT) in a child with Fanconi Anemia. In 1991, Rubinstein et al. established an unrelated donor CB bank, and in 1993, the first unrelated CBT used a unit from this bank. Since that time, >40 000 CBTs have been performed worldwide. Early outcomes of CBT were mixed and demonstrated the importance of cell dose from the CB donor. We hypothesized that improvements in CB banking and transplantation favorably impacted outcomes of CBT today and performed a retrospective study combining data from Eurocord and Duke University in 4834 children transplanted with a single unrelated CB unit (CBU) from 1993 to 2019. Changes in standard transplant outcomes (overall survival [OS], disease free survival [DFS], acute and chronic graft-versus-host disease [GvHD], treatment related mortality [TRM], and relapse) over 3 time periods (1: <2005; 2: 2005 to <2010; and 3: >2010 to 2019) were studied. Increased cell dose and degree of HLA matching were observed over time. OS, times to engraftment, and DFS improved over time. The incidence of TRM and GvHD decreased while the incidence of relapse remained unchanged. Relative contributions of cell dose and HLA matching to transplant outcomes were also assessed and showed that HLA matching was more important than cell dose in this pediatric cohort.

Nonmyeloablative Alternative Donor Transplantation for Hodgkin and Non-Hodgkin Lymphoma: From the LWP-EBMT, Eurocord, and CIBMTR.

PURPOSE: To compare the outcomes of patients with Hodgkin or non-Hodgkin lymphoma undergoing nonmyeloablative haploidentical or unrelated cord blood (UCB) hematopoietic cell transplantation. PATIENTS AND METHODS: We retrospectively studied 740 patients with Hodgkin lymphoma (n = 283, 38%) and non-Hodgkin lymphoma (n = 457, 62%) age 18-75 years who received transplantations from 2009 to 2016. Data were reported to the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation, Eurocord, or Center for International Blood and Marrow Transplant Research. Of the 526 patients who received haploidentical transplantation, 68% received bone marrow and 32% received peripheral blood. All patients received a uniform transplantation conditioning regimen (2 Gy of total-body irradiation, cyclophosphamide, and fludarabine) and graft-versus-host disease prophylaxis (calcineurin inhibitor and mycophenolate). In addition, patients who received a haploidentical transplantation received posttransplantation cyclophosphamide. RESULTS: Compared with haploidentical bone marrow and peripheral-blood transplantations and adjusted for age, lymphoma subtype, and disease status, survival was lower after UCB transplantation (hazard ratio [HR], 1.55; P = .001; and HR, 1.59; P = .005, respectively). Similarly, progression-free survival was lower after UCB transplantations compared with haploidentical bone marrow and peripheral-blood transplantations (HR, 1.44; P = .002; and HR, 1.86; P < .0001), respectively. The 4-year overall and progression-free survival rates after UCB transplantation were 49% and 36%, respectively, compared with 58% and 46% after haploidentical bone marrow transplantation and 59% and 52% after peripheral-blood transplantation, respectively. Lower survival was attributed to higher transplantation-related mortality after UCB transplantation compared with haploidentical bone marrow and peripheral-blood transplantation (HR, 1.91; P = .0001; and HR, 2.27; P = .0002, respectively). CONCLUSION: When considering HLA-mismatched transplantation for Hodgkin or non-Hodgkin lymphoma, the data support haploidentical related donor transplantation over UCB transplantation.

Assessing Breast Cancer Risk Estimates Based on the Gail Model and Its Predictors in Qatari Women.

BACKGROUND: The Gail model is the most widely used breast cancer risk assessment tool. An accurate assessment of individual's breast cancer risk is very important for prevention of the disease and for the health care providers to make decision on taking chemoprevention for high-risk women in clinical practice in Qatar. AIM: To assess the breast cancer risk among Arab women population in Qatar using the Gail model and provide a global comparison of risk assessment. SUBJECTS AND METHODS: In this cross-sectional study of 1488 women (aged 35 years and older), we used the Gail Risk Assessment Tool to assess the risk of developing breast cancer. Sociodemographic features such as age, lifestyle habits, body mass index, breast-feeding duration, consanguinity among parents, and family history of breast cancer were considered as possible risks. RESULTS: The mean age of the study population was 47.8 ± 10.8 years. Qatari women and Arab women constituted 64.7% and 35.3% of the study population, respectively. The mean 5-year and lifetime breast cancer risks were 1.12 ± 0.52 and 10.57 ± 3.1, respectively. Consanguineous marriage among parents was seen in 30.6% of participants. We found a relationship between the 5-year and lifetime risks of breast cancer and variables such as age, age at menarche, gravidity, parity, body mass index, family history of cancer, menopause age, occupation, and level of education. The linear regression analysis identified the predictors for breast cancer in women such as age, age at menarche, age of first birth, family history and age of menopausal were considered the strong predictors and significant contributing risk factors for breast cancer after adjusting for ethnicity, parity and other variables. CONCLUSION: The current study is the first to evaluate the performance of the Gail model for Arab women population in the Gulf Cooperation Council. Gail model is an appropriate breast cancer risk assessment tool for female population in Qatar.

An assessment of reliability and validity of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 among breast cancer patients in Qatar.

INTRODUCTION: Breast cancer has been the most common cancer type that affects women worldwide and subsequent treatment is often associated with considerable psychological and quality of life (QoL). AIM: This study aimed to assess psychometric properties of the Arabic version of the European Organization for Research and Treatment of Cancer (EORTC) general QoL questionnaire (QLQ-C30) for breast cancer patients in Qatar. MATERIALS AND METHODS: This is a cross-sectional hospital-based study conducted on 678 breast cancer patients using Arabic version of the EORTC QLQ-C30 tool. RESULTS: The mean age of women was 47.7 ± 10.2 years and 33.4% of women had consanguineous parents. Six subscales out of the nine met the standards of reliability with coefficients ranging from 0.55 to 0.89. The mean score of all functioning scales was high >55. Advanced breast cancer stages of III-IV had higher symptomatic scores significantly than those in early stages for the physical function, cognitive, fatigue, insomnia, appetite loss, constipation, and financial difficulties. Correlation coefficients between each item ranged from -0.113 to 0.960, and item 21 (tense) and item 23 (irritable) had strongest negative correlations with their corresponding emotional functioning subscale, whereas items 29 (physical condition) and 30 (overall QoL) had the strongest positive correlation with Global Health/QoL subscale. Item 6 (limited work) showed a higher correlation with fatigue (r = 0.749). Likewise, item 19 (pain interfered with daily activities) of the pain subscale had higher correlations with physical functioning, role functioning, and fatigue subscales. CONCLUSION: Qatari Arabic version of the EORTC QLQ-C30 showed acceptable psychometric properties, which is a reliable and valid instrument, that can be used by oncologists.

Improving the outcome of leukemia by natural killer cell-based immunotherapeutic strategies.

Blurring the boundary between innate and adaptive immune system, natural killer (NK) cells are widely recognized as potent anti-leukemia mediators. Alloreactive donor NK cells have been shown to improve the outcome of allogeneic stem-cell transplantation for leukemia. In addition, in vivo transfer of NK cells may soon reveal an important therapeutic tool for leukemia, if tolerance to NK-mediated anti-leukemia effects is overcome. This will require, at a minimum, the ex vivo generation of a clinically safe NK cell product containing adequate numbers of NK cells with robust anti-leukemia potential. Ideally, ex vivo generated NK cells should also have similar anti-leukemia potential in different patients, and be easy to obtain for convenient clinical scale-up. Moreover, optimal clinical protocols for NK therapy in leukemia and other cancers are still lacking. These and other issues are being currently addressed by multiple research groups. This review will first describe current laboratory NK cell expansion and differentiation techniques by separately addressing different NK cell sources. Subsequently, it will address the mechanisms known to be responsible for NK cell alloreactivity, as well as their clinical impact in the hematopoietic stem cells transplantation setting. Finally, it will briefly provide insight on past NK-based clinical trials.

The role of vitamin D deficiency and osteoporosis in breast cancer.

AIM: Epidemiological studies suggest an association between vitamin D and calcium intake and breast cancer. The aim of this study was to determine the association of breast cancer with vitamin D deficiency and osteoporosis according to menopausal status and to examine vitamin D and bone mineral density (BMD) levels in breast cancer patients. METHODS: This was an observational cohort hospital-based study. It included 635 patients with breast cancer. Socio-demographic information, type of consanguinity, menopause status, medical history, lifestyle habits, dietary intake, BMD measurements and vitamin D levels were collected. Descriptive and univariate analyses were performed. RESULTS: Of the studied patients, 36.1% were Qataris, 63.9% non-Qatari Arabs, 40% premenopausal women, 20.9% university graduates and 37.2% housewives. Overall, 31.8% of breast cancer women were affected with osteopenia/osteoporosis. Vitamin D deficiency (10.7% vs. 7.9%) and severe vitamin D insufficiency (39.2% vs. 32.5%) were higher in postmenopausal women than premenopausal women (P < 0.001). Low physical activity (< 30 min/day) was observed among vitamin D deficient (46.8%) and osteoporotic (45%) women. Dietary intake of vitamin D was significantly lower in vitamin D deficient women; these included dairy products (33.1%), milk (38.6%), seafood (39.6%), (P < 0.001) and for osteoporotic women, dairy products (46%), calcium (21.3%), milk (36.1%), yoghurt (37.6%), cheese (37.6%) and sea food (34.7%) (P < 0.001). CONCLUSION: The present study findings revealed a high prevalence of vitamin D deficiency and osteoporosis in breast cancer patients. Also, the dietary intake of vitamin D and calcium was significantly lower in breast cancer women.

Impacts of family history and lifestyle habits on colorectal cancer risk: a case-control study in Qatar.

BACKGROUND: Associations between family history of colorectal cancer (CRC) in first degree relatives and risk of developing cancer have been well defined, but interactions with environmental, lifestyle and dietary factors are much less clear. AIM: The aim of this study was to evaluate family history, lifestyle and dietary factors associated with developing colorectal cancer in an Arab population. DESIGN: This matched case-control study was conducted from August 2008 to February 2009 in Al-Amal Hospital and Primary Health Care Centers in Qatar. SUBJECTS AND METHODS: The study covered 146 colorectal cancer patients from Al-Amal hospital and 282 healthy subjects matched by age and gender as controls from primary health care centers. The questionnaire included socio-demographic information, type of consanguinity, medical history, lifestyle habits, and dietary intake. Of the selected 185 colorectal cancer cases, 146 (78.9%) agreed to participate in the study, whereas from the 350 selected controls, 282 (80.6%) gave consent. RESULTS: The mean age of cases was 54.1±12.4 and of controls 53.1±13.1. Among the life style factors, being overweight and obese (60.2%; 30.1% p=0.006), having a smoking habit (26.7%, p=0.025), and consuming bakery items (78.8% p<0.001) and soft drinks (28.7% p<0.02), were positively associated with CRC. The majority of the studied cases and controls were consuming fresh fruits (87.7% vs 85.5%), fresh vegetables (95.2% vs 95%) and green salad (91.1% vs 89.4%) regularly. Family history of CRC (41.8%) was significantly higher in colorectal patients than in controls (29.1%) (p<0.01). Parental consanguinity was observed more frequently in colorectal cancer patients (35.6%). Multivariate stepwise logistic regression analysis showed that smoking, BMI, family history, consuming bakery and soft drinks were significant predictors of development of colorectal cancer. CONCLUSION: The present study revealed family history and parental consanguinity to be strongly associated with the development of colorectal cancer. Age, gender, a sedentary lifestyle, and being overweight were also positively linked with CRC risk.

Fatal Strongyloides stercoralis hyper-infection in a patient with multiple myeloma

Strongyloides stercoralis (S.S.) is a human intestinal parasite, which may lead to complicated strongyloidiasis. We report a case of disseminated strongyloidiasis following the treatment of myeloma. The patient developed skin lesions, respiratory distress, aseptic meningitis and bacterial and fungal sepsis. The diagnosis of strongyloidiasis was established through endotracheal tube secretions. Despite the treatment with Ivermectin and Albendazole, the outcome was fatal. The value of screening for strongyloidiasis is unclear but may be of benefit in patients with hematological malignancies from high endemic areas.

Two Ocular Infections during Conventional Chemotherapy in a Patient with Acute Lymphoblastic Leukemia: A Case Report.

Viral retinitis due to cytomegalovirus (CMV) infection is rare in patients with acute leukemia who did not receive hematopoietic stem cell transplantation. We report a case of CMV retinitis that developed in a 49-year-old patient with acute lymphoblastic leukemia. The patient was treated with salvage chemotherapy using a hyper-CVAD regimen and did not receive hematopoietic stem cell transplantation. The incidence of CMV retinitis in this subgroup of patients is not described in literature. He had a very complicated course during chemotherapy but was successfully treated, with preservation of visual acuity, and to date he is in complete remission. Interestingly, prior to CMV retinitis, the patient had been diagnosed with and treated for candida retinitis. This case shows the importance of eye examination and care in patients diagnosed with hematological malignancies.

Fatal Strongyloides stercoralis hyper-infection in a patient with multiple myeloma.

Strongyloides stercoralis (S.S.) is a human intestinal parasite, which may lead to complicated strongyloidiasis. We report a case of disseminated strongyloidiasis following the treatment of myeloma. The patient developed skin lesions, respiratory distress, aseptic meningitis and bacterial and fungal sepsis. The diagnosis of strongyloidiasis was established through endotracheal tube secretions. Despite the treatment with Ivermectin and Albendazole, the outcome was fatal. The value of screening for strongyloidiasis is unclear but may be of benefit in patients with hematological malignancies from high endemic areas.

Do we need to maximise the breast cancer screening awareness? Experience with an endogamous society with high fertility.

BACKGROUND: In the State of Qatar, breast cancer has become the most common form of cancer among women. The aim of this study was to explore knowledge, attitude and practice about breast cancer and to identify potential barriers to screening procedures among women. METHODS: This multistage sampling cross sectional survey in primary health care centers and the outpatient department of the Women's Hospital in the State of Qatar targeted a representative sample of 1,200 Qatari women aged between 30 to 55 years of age during the period from December 2008 to April 2009. A total 1,002 subjects (83.5%) consented to participation. Face to face interviews were conducted with a designed questionnaire covering knowledge about breast cancer, attitudes and practices of breast cancer screening. Socio-demographic variables were included. RESULTS: The majority of Qatari women demonstrated an adequate knowledge about breast cancer, with a significant relation to education status. Almost three quarters were aware that breast cancer is the most common cancer in women. A good proportion knew that nipple retraction (81.2%) and discharge of blood (74.6%) are warning signs. Of the studied Qatari women, 24.9% identified breast self examination, 23.3% clinical breast examination (CBE) and 22.5% mammography as methods for detection of breast cancer. The frequently reported barriers among the Qatari women were asking any doctor/nurse how to perform breast self examination (57.3%), embarrassment about CBE (53.3%) and fear of mammography results (54.9%). Univariate and multivariate logistic regression analysis showed that family history, level of education, living in an urban area and having medical check-ups when healthy were significant predictors for CBE and mammography. CONCLUSION: The study findings revealed that although Qatari women had adequate general knowledge about breast cancer, the screening rates for BSE, CBE and mammography were low, these being performed most frequently by young Qatari women with a higher level of education.

Impact of consanguinity on cancer in a highly endogamous population.

BACKGROUND: Many epidemiological studies have indicated that inbreeding has little or no effect on the incidence of cancer. Due to the high prevalence of consanguinity in Qatar (54%), its influence may nevertheless be of special importance. AIM: The aim of this study was to examine whether parental consanguinity affects the risk of cancer in a local Arab highly inbred population. DESIGN: Matched case-control study. SETTING: The study was carried out in Al-Amal cancer hospital and primary health care centers in Qatar over a period from August 2008 to February 2009. SUBJECTS AND METHODS: The study included 370 Qataris and other Arab expatriates with various types of cancers and 635 controls matched by age and ethnicity. A questionnaire that included socio-demographic information, type of consanguinity, medical history, and tumor grade was designed to collect the information of cases and controls. RESULTS: The study revealed that the rate of parental consanguinity was similar in both cases (29.5%) and controls (29.9%) with a higher inbreeding coefficient in controls (0.017-/+0.03), compared to cancer patients (0.0155-/+0.03). Other Arab expatriates had a higher incidence of cancer (61.1%) than Qataris (38.9%). The inbreeding coefficient was higher in male cancer patients (0.0189-/+0.03), but lower in female cancer patients (0.014-/+0.03) as compared to controls. Controls were more inbred in the overall studied subjects (23.6%) and women (23.8%) than cases. The coefficient of inbreeding was lower in patients with breast (0.014), skin (0.012), thyroid (0.008) and female genital (0.014) cancers, whereas it was higher in cases for leukemia and lymphoma (0.018), colorectal (0.025) and prostate (0.017), with no significant difference between cases and controls. No significant differences were observed between cases and controls in the parental consanguinity, mean coefficient of inbreeding and proportion of more inbred subjects. CONCLUSIONS: The study findings revealed that although the consanguinity rate is high in our Arab population, it has no effect on the incidence of cancers overall. However, there was an increased risk found for leukemia and lymphoma, colorectal and prostate cancer groups, but a reduced risk in breast, skin, thyroid and female genital cancer groups.