Ahmad Alhuraiji

Viral hepatitis B and C in HIV-infected patients in Saudi Arabia.

BACKGROUND AND OBJECTIVES Hepatitis B and C are among the leading causes of death in human immunodeficiency virus (HIV)-infected patients. Prevalence data on viral hepatitis B and C in HIV-infected people in the region of Middle East and North Africa are scarce. We report the prevalence of viral hepatitis B and C in HIV-infected patients in Saudi Arabia. DESIGN AND SETTINGS Data on all HIV patients who attended HIV Program at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, were kept longitudinally. For the purpose of this report, patients enrolled in the Program between January 1985 and December 2010 were included. METHODS Data on all HIV patients who received HIV care at age 18 and older between January 1985 and December 2010 were collected. Data were collected from patients’ charts at our medical records department and electronically from the electronic health records and HIV database. We excluded patients who were deceased prior to completing work-up, lost follow-up, or acquired HIV perinatally. RESULTS Among 341 HIV-infected patients, hepatitis C infection was found in 41 (12%) patients. The commonest risk factor for hepatitis C virus and HIV acquisition was blood/blood product transfusion in 24 (60%) patients, of these 21 (88%) were hemophiliacs, followed by heterosexual transmission in 9 (22%) patients. The commonest genotype was genotype 1 observed in 18 patients (44%) followed by genotype 4 in 6 (15%) patients. Hepatitis B surface antigen was found in 11 (3%) patients. The commonest risk factor for hepatitis B virus and HIV acquisition was heterosexual transmission in 8 (73%) patients, followed by blood/blood product transfusion in 2 (18%) patients. CONCLUSION The prevalence of hepatitis C virus and hepatitis B virus infections are, respectively,10 and 20 times higher among HIV-infected patients than in the general population.

Donor-derived extramedullary acute promyelocytic leukemia post kidney transplant.

Dear Editor, Here, we describe what to our knowledge is the only case in the literature of donor kidney-derived extramedullary acute promyelocytic (EM-APL). A 54-year-old physician with diabetes mellitus, hypertension, and ischemic heart disease, who had received a renal transplant of indeterminate origin for end stage kidney disease in China 2 years before presentation, was referred to our hospital with gross hematuria, deteriorating renal function, jaundice, and multiple subcutaneous nodules. PET CT scan of the body revealed multiple FDG avid masses as shown in Fig. 1a. Biopsy of the transplanted kidney and subcutaneous nodule (FNA) was consistent with granulocytic sarcoma based on flow performed on the submitted specimen (axillary mass) showing a population of cells in the blast gate that co-express MPO, CD11b, CD13, CD33, CD34, CD38, and CD117 and HLA-DR (dim). Bone marrow was uninvolved and a FISH panel including t(15;17) was negative. Attempted cytogenetic analysis from FNA of the nodules failed. A resection of the kidney was offered but the patient declined, and immunosuppression was continued with lowdose FK506 and prednisone; MMF was stopped. The final diagnosis at that stage was granulocytic sarcoma. Given the comorbidities, he was given upfront idarubicin and cytarabine “2+5” with a suboptimal response based on PET scan; then, he received salvage fludarabine/Ara-c (FA) protocol resulted in complete metabolic response. As per standard operating procedure at our hospital, PML-RARa is not sent from a diagnostic tissue sample other than bone marrow. In order to characterize the disease further, a FISH panel on the axillary biopsy was done and revealed positivity for t(15;17). The patient was then given ATRA/idarubicin (AIDA) induction followed by 25 doses of arsenic trioxide (ATO) consolidation and then maintenance ATRA; mercaptopurine and methotrexate were not given due to cytopenias. As the initial lesion seemed to be in the transplanted kidney, we sought to determine whether the leukemia may have been of donor origin. In order to address this hypothesis, DNA was extracted from the previously excised axillary block. This was compared with DNA from the patient’s blood. To our surprise, DNA by short tandem repeat analysis revealed that axillary mass was not of recipient origin as shown (Fig. 1b). Eighteen months on since first presentation, he has no demonstrable disease based on PET scan with good quality of life and stable renal function. A case reported in Blood by Girsberger et al. described a case of donor kidney derived AML [1]. Kidney transplant recipients are at increased risk for development of malignancy compared with the general population [2]. There are case reports of AML post solid organ transplantation [3, 4]. Donor-derived APL has been reported [5]; however, the aleukemic extramedullary presentation in our case is unique. Treatment of acute leukemia in solid organ transplant remains one of the main challenges facing the hematologist with sparse literature focusing on this issue. A. Alhuraiji (*) :W. Chebbo :G. El-Gohary :N. Chaudhri : F. Almohareb :K. Ibrahim : S. A. Osman Hematology Section, Oncology Centre, KFSHRC, Riyadh 11211, Saudi Arabia e-mail: aalhuraiji@gmail.com

Life after ponatinib failure: outcomes of chronic and accelerated phase CML patients who discontinued ponatinib in the salvage setting

Abstract Ponatinib is a pan-tyrosine kinase inhibitor (TKI) with efficacy in multirefractory CML patients who have failed other TKIs. Despite excellent response rates, resistance or intolerance may develop. We conducted a retrospective review of the outcome of patients with chronic (CP) and accelerated (AP) phase CML refractory to prior TKI who discontinued ponatinib for resistance or intolerance. Nineteen CP patients, discontinued due to resistance (n = 13), toxicity (n = 5) and to pursue stem cell transplantation (n = 1). At discontinuation, 14 were still in CP, three had progressed to AP and two to blast phase (BP). Three CP patients improved their cytogenetic response (CyR) to complete CyR (CCyR), two after SCT and one on omacetaxine. None of the 12 patients, without a major cytogenetic response at ponatinib discontinuation, including all patients treated with subsequent TKIs, responded to therapy. Seventeen AP patients, stopped ponatinib due to resistance (n = 15) or intolerance (n = 2). At discontinuation, 14 were still in AP and three had progressed to BP. Four patients were treated with SCT and one achieved major molecular response. None of the 12 patients treated with non-SCT approaches responded to subsequent therapy. Median survival for all patients was 16.6 months after ponatinib discontinuation (31, 9 and 13 months for patients in CP, AP and BP, respectively). Median survival was 60 months for patients who discontinued ponatinib for toxicity and 11 months for those who discontinued for resistance. Long-term outcome of patients with ponatinib failure are poor with estimated one-year OS and EFS rates of 54% and 40%, respectively. New treatment options are required for this subset of patients.

New-onset diabetes after kidney transplantation: Incidence, risk factors, and outcomes

Many patients develop new-onset diabetes after kidney transplantation (NODAT). Its incidence and epidemiology are unknown in the Saudi population. We aimed to study the incidence, epidemiology, and outcomes of kidney transplant recipients who developed NODAT. This is a retrospective study of all adults who received kidney transplant between January 2003 and December 2009. NODAT was defined according to the criteria outlined in the 2003 International Consensus guidelines. A total of 500 patients were included in this study, 54% were male patients. One hundred thirty-six patients (27%) developed diabetes (NODAT group). In the univariate analysis, patients were older in the NODAT group (P <0.001), were of higher weight (P = 0.006), and had positive family history of diabetes (P = 0.002). Similarly, more patients in this group had impaired glucose tolerance before transplant (P = 0.01) and history of hepatitis C infection (P = 0.005). In the multivariate analysis, older age [odds ratio (OR) 1.06], family history of diabetes (OR 1.09), hepatitis C infection (OR 1.92), and impaired fasting glucose (OR 1.79) were significant risk factors for the development of NODAT. Mortality was 6% in the NODAT group and 0.5% in the non-diabetic group had died (P <0.001). Graft survival was not different between the groups (P = 0.35). In conclusion, there is a significant risk of developing diabetes after renal transplantation. Patients are at higher risk if they are older, have a family history of diabetes, pre-transplant impaired fasting/random glucose, and hepatitis C virus infection.

Daratumumab (DARA) is Highly Effective Therapeutic Intervention in Patients with AL Amyloidosis (AA)

therapy significantly prolonged median PFS (36 vs. 19 months, HR:0.56; p1⁄40.03) compared to no maintenance. Conclusions: In the largest cohort of t(14:16) patients described to date, t(14;16) characterizes a group of high-risk MM patients with poor PFS and OS. ASCT-1 in first remission and maintenance therapy prolonged survival of patients with t(14;16).

Acute lymphoblastic leukemia secondary to myeloproliferative neoplasms or after lenalidomide exposure

Philadelphia‐negative (Ph−) myeloproliferative neoplasms (MPN) do rarely transform to acute lymphoblastic leukemia (ALL). While causality is difficult to establish, a few cases of ALL arising after exposure to lenalidomide for registered indications (multiple myeloma, myelodysplastic syndrome with 5q deletion) have been described in the literature.

Immunofluorescence staining with an antipromyelocytic leukemia antibody for a rapid diagnosis of acute promyelocytic leukemia.

http://dx.doi.org/10.1016/j.hemonc.2016.05.004 1658-3876/ 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). * Corresponding author at: Department of Leukemia, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, FC4.3062, Unit 428, Houston, TX 77030, USA. E-mail address: aalhuraiji@mdanderson.org (A. Alhuraiji).

Elevated alanine aminotransferase levels in HIV-infected persons without hepatitis B or C virus coinfection.

BACKGROUND Mortality related to human immunodeficiency (HIV) has improved with the use of antiretroviral therapy; however, liver disease–related mortality remains a major concern for the HIV population. Elevation of alanine aminotransferase (ALT) has been noted in HIV-infected persons even without viral hepatitis infection. OBJECTIVE The objective of this study was to determine the incidence and prevalence of chronic alanine ALT elevation among patients infected with HIV who are negative for hepatitis B or C infection. DESIGN Retrospective chart review. SETTINGS We reviewed the medical records of all patients infected with HIV who had been treated from November 2002 to December 2010. PATIENTS AND METHODS Patients with an unknown or positive HBV or HCV infection status were excluded. We identified patient demographics, route of transmission, peak viral load, and nadir CD4 count. RESULTS We followed 440 patients for up to 2265 person-years. A total of 123 patients developed chronically elevated ALT levels, with an incidence of 5.8 cases per 100 person-years. Chronically elevated ALT levels were associated with high HIV viral load, mean body mass index, and diabetes mellitus. We found exposure to lamivudine in 58% of the patients, efavirenz in 41%, and zidovudine in 38%. Abdominal ultrasounds revealed fatty liver in 20 of 39 (51%) of the patients. CONCLUSION Among patients without viral hepatitis coinfection, the prevalence and incidence of chronic elevated ALT levels were high and accompanied by high HIV RNA levels and increased BMI. LIMITATIONS The limitations of this report are its retrospective nature and lack of a control group.