Rawad S Rihani

Abstract: BACKGROUND: High frequency oscillatory ventilation (HFOV) has been successfully used in the management of acute respiratory distress syndrome (ARDS) in children. The aim of our study is to determine its effectiveness in pediatric patients with cancer or post hematopoietic stem cell transplantation (HSCT) diagnosed with ARDS. PROCEDURE: A retrospective case review, in a pediatric intensive care unit (PICU) in a tertiary-care oncology center in Amman, Jordan. Patients included were children with cancer and/or receiving allogeneic HSCT who were diagnosed with ARDS and placed on HFOV from January 2007 to February 2009. RESULTS: Data from 12 pediatric oncology patients on HFOV were analyzed for demographics, oncological diagnosis, PRISM III scores, ventilator settings before switching to HFOV and 24 hours after switching, complications, and outcomes. Alveolar-arterial oxygen (A-a) gradient and oxygen index (OI) were calculated, and pressure of arterial CO(2) (PaCO(2) ) was measured before and 24 hours after switching. Endpoints were successful extubation and discharge, or death while intubated. After 24 hours on HFOV, the A-a gradient decreased significantly in all patients (from a median of 564-267 torr; P=0.001). OI decreased in all but two patients who died (median 17); PaCO(2) decrease was not significant. Five patients died (two of them post-HSCT) and the 7 (58%) survivors were weaned from HFOV (median, 9 days) and discharged. CONCLUSIONS: HFOV improves gas exchange and is useful in managing critically ill children with cancer and post-HSCT patients who develop ARDS.

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Abstract: Abstract BACKGROUND: Accurate data about childhood acute lymphoblastic leukemia (ALL) in low- and middle-income countries are lacking. Our study is designed to assess survival of childhood ALL at King Hussein Cancer Center (KHCC) using modified St. Jude Children's Research Hospital protocols. PATIENTS AND METHODS: We reviewed the medical records of children 1-18 years of age who were diagnosed with ALL and treated at KHCC from January 2003 through December 2009. Disease characteristics and outcome were analyzed. RESULTS: Over a 7-year period, 300 children with ALL were treated. One hundred and seventy-three (57.7%) were males and 127 (42.3%) were females. The median age at diagnosis was 5 years. One hundred and fifty-seven (52.3%) children were classified as low-risk, 118 (39.3%) were standard-risk and 25 (8.3%) were high-risk. Two hundred and sixty-two (88.5%) children had pre-B cell phenotype and 34 (11.5%) had T-cell phenotype. Two hundred and seventy-three (91.3%) children were classified as having CNS I disease, 24 (8%) had CNS II, and 2 (0.67%) had CNS III. Cytogenetic abnormalities included: t(12;21) in 30 (12%) children and t(9;22) in 18 (7.4%). Four (1.3%) children died in induction, 6 (2%) died in first remission and 27 (9%) relapsed. After a median follow-up of 34.5 months (range 0.32-84.5), the estimated 5-year event free survival and overall survival were 80% and 89%, respectively. CONCLUSION: Treatment protocols developed by major cooperative groups and institutions to treat childhood ALL was successfully adapted and suggest that such an approach may be useful in other low- and middle-income countries.

Abstract: Unrelated cord blood transplantation can restore hematologic and immunologic functions in patients with Chediak-Higashi syndrome. Pediatr Transplantation 2011. © 2011 John Wiley & Sons A/S. Abstract:  CHS is a rare hereditary fatal disease, if not treated. APs occur in 85% of patients and are usually the main cause of mortality, and HSCT from HLA-matched related and unrelated donors is the only effective treatment for CHS and prevents recurrences of APs. We reviewed the records of three patients with CHS who underwent UCBT at KHCC. Records were examined for clinical features at the time of UCBT, conditioning regimens, morbidities, and outcomes. Conditioning comprised BU, cyclophosphamide, horse ATG, and etoposide. All patients tolerated the conditioning well. Two patients are alive, one with mixed and the other with full donor chimerism; hematologic and immunologic defects of CHS have been corrected in both patients. They show no evidence of recurrences of APs and have normal growth and development. In patients with CHS who lack HLA-matched related and unrelated donors, UCBT is a suitable alternative source of stem cells to restore immunologic and hematologic functions and prevent AP relapses, even in mixed chimeric states. Long follow-up and close monitoring are essential to evaluate the long-term benefits of using UCBT in patients with CHS.

Abstract: We analyzed data from 18 898 adults (age ≥20 years) and 2836 children/adolescents reported in the Surveillance, Epidemiology and End Results (SEER) database as having Hodgkin lymphoma (HL), diagnosed from 1988 to 2005. The nodular sclerosis subtype was significantly more common in the pediatric age group (76% in children/adolescents vs. 61% in adults, p < 0.001). The mixed cellularity subtype was more prevalent in children <10 years old (22%), but less likely in older children/adolescents (8.5%). Systemic symptoms were reported in 39% of children/adolescents and in 48% of adults (p < 0.001). Children/adolescents had significantly better HL-specific survival than adults (5-year survival rate, 96% ± 0.4% vs.88% ± 0.3%, p < 0.001). Using a Cox proportional-hazards regression model in patients with classical HL, the prognostic factors significantly impacting survival were age, histology, stage, B symptoms, year of diagnosis, and race. The only adverse prognostic factors that were significant when this analysis was restricted to children/adolescents were stage IV disease and the presence of B symptoms. In conclusion, several differences in clinicopathologic features and outcomes were identified between children/adolescents and adults with HL, and this was particularly noted in young children (<10 years).

Abstract: A 7-year-old male with Fanconi Anemia who developed primary graft failure following one antigen-mismatched unrelated cord blood transplantation and a nonradiation-based conditioning, underwent a second hematopoietic stem cell transplantation (HSCT) from his 2-loci mismatched haploidentical father, using a nonradiation-based regimen, 79 days after the first HSCT. A sustained hematological engraftment was achieved at 9 days post-second HSCT. At 15 months post-second HSCT; the patient demonstrated normal blood counts, sustained donor chimerism, and no evidence of GVHD. Haploidentical HSCTs as primary or secondary sources of stem cells, with appropriate T-cell depletion, may be a readily available option in the absence of HLA-matched related or unrelated donors.

Abstract: BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare malignancy in the United States, which is considered a low-risk country. METHODS: We searched the surveillance, epidemiology, and end results (SEER) database for patients with NPC who were diagnosed from 1988 to 2006. We compared the clinical features and outcomes of children and adolescents (<20 years old) and adults. RESULTS: The incidence for children and adolescents was 0.5 per million person-years versus 8.4 in adults. NPC was less rare in black children and adolescents (incidence, 1.5 per million person-years). Our search criteria retrieved 129 children and adolescents and 5,885 adults. Black children and adolescents represented 34.9% of patients below the age of 20 years. Younger patients had distinct features with advanced stages more frequently observed (31% and 46% of children and adolescents had stages III and IV, respectively) and 87% had WHO type III histology. Outcome was better in children and adolescents with 5-year NPC-specific survival of 83% +/- 3.9% compared to 62% +/- 0.8% in adults (P < 0.001). In a multivariate model, the following factors affected the outcome: age, race, stage, and histologic type. Young adults (20-45 years old) had almost double the risk of NPC-specific mortality when compared to children and adolescents [hazards ratio (HR), 1.93; P = 0.0077]. Children and adolescents with NPC were at higher risk of getting second cancer than adults (observed-to-expected ratio of 4.36 in children and adolescents; vs. 1.41 in adults; both were significantly higher than general population). CONCLUSION: Despite the use of similar treatment approaches, NPC in children and adolescents may have different biologic features. Young patients are at higher risk of developing therapy related complications, including second cancer.

Abstract: BACKGROUND:: Studying secondary hematological malignancies in a large cohort of patients can help predict risks and trends associated with current therapies. METHODS:: The authors analyzed data from the Surveillance, Epidemiology, and End Resultsecondary 9 (SEER-9) database on patients with a primary malignancy (diagnosed before the age of 20 years) between 1973 and 2005 who developed a secondary hematological malignancy. Primary cancer and histological subtype, incidence, risk factors, outcomes, and changes in risk patterns of secondary hematological malignancies were analyzed for 1973 to 1985, 1986 to 1995, and 1996 to 2005. Standardized incidence ratios (SIRs) of observed to expected cancers were calculated. RESULTS:: Of 34,867 patients with a histology-confirmed primary malignancy, 111 developed secondary hematological malignancies (median, 44 months). Lymphoma was the commonest primary cancer (n = 47). The main histological subtype of secondary hematological malignancy was acute myeloid leukemia (AML) (49%), which had the shortest median latency time and the worst 5-year survival (18% +/- 5.3%; P = .044). Secondary Hodgkin lymphoma had the best 5-year survival (83% +/- 15%). The 5-year overall survival for patients with secondary hematological malignancies was 31% +/- 4.7%. The risk of secondary AML steadily increased from 1986 to 2005, whereas SIRs for acute lymphoblastic leukemia did not change over time. Non-Hodgkin lymphoma, the second most common secondary hematological malignancy, occurred at a median of 112 months, and its risk steadily increased over time periods. CONCLUSIONS:: Childhood cancer survivors are at increased risk of developing secondary hematological malignancies, particularly secondary AML. This risk has continued to rise even in recent years, emphasizing the need to study other factors contributing to secondary hematological malignancies and closely monitor these patients. Cancer 2010. (c) 2010 American Cancer Society.

Abstract: BACKGROUND: Despite significant improvement in the outcome of patients with Ewing Sarcoma Family of Tumors (ESFT), second malignancies remain a problem that may compromise the outcome of some survivors. The Surveillance, Epidemiology and End-Results (SEER) database offers an opportunity to study second malignancies in a population-based cohort of patients. METHODS: Cancer incidence rates were compared between the ESFT survivors and the general population using observed-to-expected ratios (O/E). Also, we studied the characteristics of patients with ESFT who developed second malignancies and compared them to those who did not. RESULTS: We studied 1,166 patients with ESFT who were diagnosed from January 1973 to December 2005. Among them, 35 (3%) patients had records of second malignancy. Patients who received radiotherapy as part of their primary therapy had a higher chance of developing a second malignancy (odds ratio, 2.55; 95% CI, 1.09 to 6.00). Most solid tumors (78%) were diagnosed more than 5 years after diagnosis of ESFT while the majority (83%) of lymphatic/hematopoietic malignancies developed within five years of diagnosis. The 5-, 10-, and 20-year probability of developing a second malignancy were 2.1% +/- 0.56%, 4.4% +/- 0.95% and 8.0% +/- 1.7%, respectively. The O/E ratio for developing a second malignancy was 4.10 (95%CI, 2.87 to 5.68) but was higher in children/adolescents (O/E, 9.94; 95%CI, 6.30 to 14.91). CONCLUSION: Having a second cancer following a diagnosis of ESFT is a known risk that may be increased by current therapies. This modest increase is justified by the benefit of these therapies in the majority of patients with ESFT.

Abstract: Bone marrow and stem cell transplantation in Jordan has been performed since the 1990s, but the first comprehensive program was established at King Hussein Cancer Center (KHCC) in March 2003. The program, in addition to other health care institutions in Amman, serves approximately 5.6 million Jordanians. Also, we treat several patients per year from neighboring Arab countries. The program at KHCC performs an average of 80 transplants per year. During the past 4 years 320 patients received transplants at KHCC; 26% of them received an autologous graft and 74% allogeneic grafts. Of the allogeneic grafts 91% were taken from matched family members, 6.7% were haploidentical from one of the parents, and 2.3% were from an unrelated donor or umbilical cord blood. The actuarial overall survival among all patients has been around 65%. The most common indication for transplantation at KHCC was leukemia/MDS followed by benign nonmalignant hematological/immune deficiency/metabolic disorders, with thalassemia major being the most common among this group. The cost of SCT is variable and depends on many factors including the type of transplant and the attending post-transplant complications. The average charge for autologous transplant (both adults and pediatrics) is 24,695 JD (one JD equals 1.42 USD), and the average charge for allogeneic transplant (both adults and pediatrics) excluding haploidentical transplant is 46,787 JD. We have not noticed any peculiar patterns of complications following BMT; however, we have seen a high incidence of chronic GVHD following minitransplant with fludarabine and single-dose TBI (Seattle protocol). At the inception of the program, invasive fungal infection mainly related to building construction, and central line complications were significant. Measures implemented to control such complications were successful to a large extent. We report our results to the EBMT group and we are accredited as an unrelated transplantation center. Although from a young program, our group has presented abstracts to international conferences.