Thrombotic thrombocytopenic purpura - analysis of clinical features, laboratory characteristics and therapeutic outcome of 24 patients treated at a Tertiary Care Center in Saudi Arabia.

OBJECTIVE: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease. The primary aim was overall response rate (ORR) assessment in the treated patients. METHODS: This retrospective study included 24 patients treated during 2006-2015. TTP patients with microangiopathic hemolysis (MAHA) and thrombocytopenia were included. We analyzed clinical features, laboratory characteristics and treatment outcomes of 24 TTP patients treated at our tertiary care center (KFMC). RESULTS: Twenty-four TTP patients (18 females; 6 males) had a mean age of 33.5±13.9 years; 22(91%) had neurologic features, 7(29%) fever, 10(42%) renal impairment; 4(20.83%) cardiac manifestations; 22(91.7%) had triad with additional neurologic abnormalities; only 2(8.2%) had pentad of TTP. Majority (54.16%) had idiopathic TTP. All patients received therapeutic plasma exchange (TPE); 23(95.8%) received adjunctive corticosteroids and 13(54.2%) received rituximab either due to refractoriness to TPE on ~day7, or earlier. Twenty-one out of 24 (87.5%) achieved complete remission (CR) without any subsequent relapse. At 22 months (median, range 1-113), 20 patients (83.3%) are alive at the time of report. Three patients died during acute episode because of sever disease or delayed treatment and one died in CR. CONCLUSION: TPE, steroids and or rituximab was very effective in preventing high risk of mortality and achieving durable CR in 87.5% of patients. More awareness is needed for early diagnosis and early referral to centers with appropriate tertiary care facilities..

De novo lymphoid blastic phase chronic myeloid leukemia: report and contemporary discussion.

OBJECTIVE: We herein describe two cases of de novo lymphoid blastic transformation in patients with no history of chronic-phase chronic myeloid leukemia (CP-CML), both of whom were labeled initially as Philadelphia positive B-Acute Lymphoblastic Leukemia (B-ALL). METHODS: The first patient was an 18-year-old male who presented with subjective fever, intentional weight loss, generalized fatigue, and headache. Investigations showed leukocytosis (312 × 10^3/ul), thrombocytopenia and anemia. Flowcytometry was consistent with B-ALL, with aberrant expression of CD13 and CD33. He was found to be positive for BCR::ABL by FISH, and karyotype confirmed the presence of the Philadelphia chromosome. He received a pediatric-inspired regimen and achieved remission with negative measurable residual disease (MRD) by flowcytometry, however with persistent cytogenetic abnormality using FISH for BCR::ABL. FISH abnormality was confirmed to be in the myeloid compartment using myeloid segregated FISH, reclassifying the disease to de novo lymphoid blastic phase CML. The second patient was a 52-year-old male who presented with fever and shortness of breath. Bilateral cervical lymphadenopathy and hepatosplenomegaly were identified on examination, and investigations showed leukocytosis (371 × 10^3/ul), anemia, and thrombocytopenia. BCR::ABL rearrangement was identified by FISH, molecular testing, and confirmed with karyotype. He was treated with Mini-CVD and Ponatinib, achieved complete remission with negative MRD by flow cytometry, however molecular studies showed BCR-ABL1 level at 58% IS indicating a persistent cytogenetic abnormality. RESULTS: De novo lymphoid blastic-phase CML can therefore be difficult to differentiate from Philadelphia positive B-ALL due to their overlapping clinical and laboratory picture, implying the need to do myeloid compartment evaluation at the time of diagnosis. CONCLUSION: With recent progress in the treatment of Philadelphia positive B-ALL, including the role of transplant with the use of novel agents, a better characterization of this disease entity in retrospective and prospective trials is warranted.

Hematopoietic stem cell transplantation in Saudi Arabia between 1984 and 2016: Experience from four leading tertiary care hematopoietic stem cell transplantation centers.

Saudi Arabia is the largest of the Arabian Gulf countries with a total population of 33.41 million as of 2017. This report summarizes the experience from four leading tertiary care hematopoietic stem cell transplantation (HSCT) centers in Saudi Arabia representing more than 90% of all HSCTs performed in the country. Between 1984 and 2016, a total of 6,184 HSCTs were performed. Of these, 3,586 HSCTs were performed in adults and 2,598 HSCTs were performed in pediatric patients. Malignancy was the main indication for transplantation (47%). While most transplants were performed from an identical sibling donor, HSCTs from cord blood, unrelated and, more recently, haploidentical donors have also been performed. Relative shortage of HSCT bed capacity is perceived to be a limiting factor in Saudi Arabia. Lately, more HSCT centers are emerging with rapid growth, which may significantly improve the access to HSCT in the country in the near future.

An Intriguing Case of Eosinophilia with FIP1L1/PDGFRA Rearrangement Who Presented as Thrombotic Thrombocytopenic Purpura.

Myeloid neoplasm with eosinophilia and FIP1-like-1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) rearrangement is a multi-organ disease with diverse clinical presentation. Thrombotic thrombocytopenic purpura (TTP) is characterized by the concomitant occurrence of often severe thrombocytopenia, microangiopathic hemolytic anemia, and a variable degree of ischemic organ damage. To our knowledge, only one case of eosinophilia with FIP1L1-PDGFRA rearrangement presented as a case of thrombotic thrombocytopenic purpura reported in the literature. We herein report a case of a young male patient with hypereosinophilic syndrome and FIP1L1-PDGFRA rearrangement who presented with asthma, transient ischemic attacks (TIA), and confusion. He had an acquired TTP that was successfully treated with plasma exchanges (PLEX), corticosteroids, rituximab, and later with the addition of imatinib mesylate (Gleevec, Novartis). He remains in complete remission on imatinib 100 mg daily for more than 28 months of follow-up.

Narrowing the gap for hematopoietic stem cell transplantation in the East-Mediterranean/African region: comparison with global HSCT indications and trends.

Hematopoietic Stem Cell Transplantation (HSCT) activity was evaluated in the African (AFR)/EMRO region and compared to the global activity for the years 2006-2013. Data were obtained from 1570 teams in the 6 WHO continental regions. Of these, 29 (1.85%) of all teams were active in 12 of the 68 AFR/EMRO countries. They reported 2.331 (3.3%) of the worldwide 71.036 HSCT, and a transplant rate of 32.8 (TR; HSCT/10 million inhabitants; worldwide 128.5). This reflects still the lowest regional TR despite an increase of 90% since 2006. HSCT activity in AFR/EMRO countries was characterized by a higher use of allogeneic compared to autologous HSCT, an almost exclusive use of family donors, including haploidentical family donors. These findings contrast with the prevalence of autologous over allogeneic HSCT, and a higher frequency of unrelated HSCT in other parts of the world. Of note, the increase by 200% in HSCT for hemoglobinopathies from 2006 to 2013 (72 per year) in the AFR/EMRO region. This reflects the specific role of HSCT for these disease categories with high prevalence and incidence in the AFR/EMRO region. This report provides information for the competent authorities to foster adequate infrastructure. It urges transplant organization to optimize their cooperation.

CD56 and RUNX1 isoforms in AML prognosis and their therapeutic potential.

Neural cell adhesion molecule (NCAM/CD56) expression in acute myeloid leukemia (AML) has been associated with extramedullary leukemia, multidrug resistance, shorter remission and survival. Recently, Bloomfield et al. published a succinct review of issues surrounding the AML prognostication and current therapeutics. However, we want to reiterate the prognostic value and therapeutic potential of CD56 that is frequently expressed in AML as was also reported by their own group earlier. In addition, novel RUNX1 isoforms contribute in controlling CD56 expression in AML cells. Anti-CD56 antibody therapy deserves exploration as an arsenal against AML patients expressing CD56. Relevantly, targeting RNA splicing machinery or RUNX1 isoform-specific siRNA may also become part of future therapeutic strategies for AML with CD56 overexpression.

Primary burkitt lymphoma of the fourth ventricle in an immunocompetent young patient.

Primary Burkitt lymphoma of the central nervous system (CNS) is rare, with only few cases reported in the literature. An 18 year-old immunocompetent male presented with multiple cranial nerves palsies and was found to have a mass predominantly in the 4th ventricle of the brain. Tumor was surgically removed and showed morphological and immunohistochemical features consistent with Burkitt lymphoma. The patient responded very well to anthracycline based chemotherapy with high dose methotrexate (HD MTX) and intrathecal (IT) chemotherapy delivered by Ommaya reservoir. Primary Burkitt lymphoma of the CNS is a rare entity that poses differential diagnostic challenge with other small round blue cell tumors.

Cold agglutinin disease in fibrolamellar hepatocellular carcinoma: a rare association with a rare cancer variant.

Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia. Although it can occur secondary to lymphoproliferative disorders and autoimmune or infectious diseases, CAD is rarely reported as secondary to solid tumors. We report a case of a woman aged 18 years diagnosed with a well-differentiated hepatocellular carcinoma of the fibrolamellar subtype, who was shown to have CAD also. Her general condition, including CAD, improved after targeted therapy with sorafenib for the hepatocellular carcinoma and only conservative measures for the CAD that consisted of avoidance of cold. In summary, although it is an extremely rare association and less common than lymphoproliferative disorders, CAD can be associated with solid tumors.

Chemotherapy and hematopoietic stem cell transplantation for adult T-cell lymphoblastic lymphoma: current status and controversies.

Adult T-cell lymphoblastic lymphoma is a relatively rare aggressive type of non-Hodgkin lymphoma with frequent involvement of extranodal sites. Because of the rarity of this malignancy, it is treated variably and often suboptimally, using approaches similar to those used for other types of aggressive non-Hodgkin lymphomas, with the consequence that outcome is often suboptimal. The collective experience in the management of adult T-cell lymphoblastic lymphoma suggests a good outcome for patients with no adverse prognostic factors who are treated with an acute lymphocytic leukemia-like treatment strategy. Patients with adverse prognostic features should be considered for more aggressive therapy-specifically, high-dose chemotherapy and hematopoietic stem cell transplantation. This article will attempt to review the current status of chemotherapy treatment programs and the relative merits of the different hematopoietic stem cell transplantation programs in this disease, particularly in relation to the pathologic and clinical features that correlate with disease prognosis.