Comparative study between chronic automated red blood cell exchange and manual exchange transfusion in patients with sickle cell disease: A single center experience from Saudi Arabia.

BACKGROUND: Red cell transfusion remains the gold standard in managing sickle cell disease (SCD) with severe complications. Offering red blood cell exchange (RBCX) either manual exchange transfusion (MET) or automated RBCX (aRBCX) can reduce the complications of chronic transfusion and maintain target Hb thresholds. This study audits the hospital experience of overseeing adult SCD patients treated with RBCX, both automated and manual, and compares the safety and efficacy. MATERIALS AND METHODS: This retrospective observational study was conducted as an audit for chronic RBCX for adult patients with SCD in 2015-2019 at King Saud University Medical City, Riyadh, Saudi Arabia. RESULTS: A total of 344 RBCX for 20 adult SCD patients who were enrolled in regular RBCX, (11/20) patients had regular aRBCX with a total of (157) sessions, and (9/20) patients had MET with a total of (187) sessions. The median level of HbS% post-aRBCX was significantly lower than MET (24.5.9% vs. 47.3%, P < 0.010). Patients on aRBCX had fewer sessions (5 vs. 7.5, P < 0.067) with better disease control. Although the median yearly pRBC units per patient for aRBCX was more than the double needed for MET (28.64 vs. 13.39, P < 0.010), the median ferritin level was 42 µg/L in aRBCX versus 983.7 µg/L in MET, P < 0.012. CONCLUSION: Compared to MET, aRBCX was more effective in reducing HbS, with fewer hospital visits and better disease control. Although more pRBCs were transfused, the ferritin level was better controlled in the aRBCX group without increasing alloimmunization risk.

Allogeneic hematopoietic stem cell transplantation in adolescent and adult patients with high-risk T cell acute lymphoblastic leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is often recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (≥CR2) and sometimes in high-risk (HR) patients in first complete remission (CR1). Between January 1995 and July 2009, 53 patients with HR T-ALL underwent allo-SCT at our institution. Median age was 18 years (range, 14-51). Thirty-two patients (60.3%) were in CR1, 18 (34%) were in ≥CR2, and 3 (5.7%) were in relapse. The cumulative incidence of nonrelapse mortality at 5 years was 22.5%. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 40.2%, and that of chronic GVHD was 43.7%. The majority of relapses (88.9%) occurred within 1 year after SCT. The cumulative incidence of relapse (CIR) at 5 years was 35.6%. CIR was 29.8% in patients in CR1, 35.3% in patients in ≥CR2 and all patients transplanted in relapse had disease recurrence post-allo-SCT (P = .000). Overall survival (OS) and disease-free survival (DFS) at 5 years were 43.5% and 41.8%, respectively. The 5-year OS was 53.5% (95% CI 34.5%-72.5%) and 5-year DFS was 52% (95% CI 33%-71%) in patients who underwent allo-SCT in CR1, compared with 31.9% (95% CI, 9%-54.8%) and 29.4% (95% CI 7.6%-51.2%) in those who underwent allo-SCT in ≥CR2. On multivariate analysis, disease status at SCT remained significantly associated with OS (P = .007), DFS (P = .002), and CIR (P = .000). The presence of extramedullary disease at diagnosis had no effect on the different outcomes. Grade II-IV acute GVHD was significantly associated with a lower OS (P = .006) and DFS (P = .01). Our data indicate that allo-SCT represents an effective treatment for HR T-ALL, particularly when performed in CR1.

Stem cell transplantation in hematological disorders. A developing country experience-impact of cost considerations.

OBJECTIVE: To describe the experience in setting up a bone marrow transplant program at Ain Shams University, Cairo, Egypt. METHODS: Sixteen patients were transplanted at Ain Shams University Bone Marrow Transplantation unit from March 2005 to January 2008. RESULTS: Sixteen patients were transplanted with a median age of 25 years. Indications for transplantation were chronic myeloid leukemia, acute myeloid leukemia, aplastic anemia, acute lymphoblastic leukemia, and aggressive lymphoma. Seven donors and 6 patients were positive for cytomegalovirus immunoglobulin G (IgG) antibody (Ab) pretransplant. Only one patient was positive for toxoplasma IgG Ab and another had a high titre for toxoplasma IgM Ab pretransplant. Two donors and 2 recipients were positive for hepatitis B antibody markers; however, none were positive for hepatitis B virus DNA by polymerase chain reaction (PCR). None of the patients or donors were positive for hepatitis C virus via PCR pre-transplant. Acute graft versus host disease (GVHD) was seen in 3 patients, while chronic GVHD was seen in 5 patients. Primary cause of death was recurrence in 2 patients and graft failure in one patient. Thirteen are alive and disease free with a median follow-up of 20 months. CONCLUSION: Although our unit is a relatively new unit, these results are comparable to those achieved in the Western world and cost a mean of US$250,000.

Extramedullary relapses after allogeneic stem cell transplantation for acute myeloid leukemia: clinical characteristics, incidence, risk factors and outcomes.

Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplant (allo-HCT) is challenging. Data on extramedullary relapse (EMR) after allo-HCT are limited. We analyzed 215 patients with AML who underwent allo-HCT in our institution between January 2005 and December 2015. We limited this retrospective review to patients who received a MA conditioning, were in complete remission (CR) at the time of transplant and who received a matched sibling transplant, all other patients were excluded to avoid heterogeneity. Seventy-seven (35.8%) patients experienced disease relapse, 45 had BMR, and 32 had EMR. The only variable that was statistically associated with EMR post allo-HCT was male sex (OR = 3.2 (1.2, 8.2), p-value = 0.01); there was a trend for association between transplant in >CR2 and EMR (OR = 0.38 (0.14, 1.06), p-value = 0.06). The median overall survival (OS) after relapse for all relapses was 10 months (95% CI 4.839-15.161). The median OS for BMR group was 8 months (95% CI 2.850-13.150) and 14 months for the EMR group (95% CI 5.776-22.224); however, this was not statistically significant, p-value = 0.4. Multivariate analysis revealed that gender, treatment modality, and time from allo-HCT to relapse (≥12 vs. <12 months) have significant association with the post-relapse death. Male gender was the only significant factor associated with EMR.

Myeloid sarcoma of the vulva post-bone marrow transplant presenting as isolated extramedullary relapse in a patient with acute myeloid leukemia.

Myeloid sarcoma is a tumor of myoblasts or immature myeloid cells occurring in an extramedullary site. Myeloid sarcoma of the female genital tract as an isolated initial presentation or isolated relapse is very rare as evidenced from a literature review. We report a case of vulvar myeloid sarcoma presenting as isolated relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplant (HSCT). A 41-year-old female diagnosed with AML M5 achieved remission with chemotherapy and underwent allogeneic HSCT from an HLA-matched sibling donor. The post-transplant period was complicated with chronic graft-versus-host disease. At 10 months post-transplant, she presented with a vulvar mass of six weeks duration. Excisional biopsy of the vulvar mass confirmed the diagnosis of myeloid sarcoma as extramedullary relapse. Bone marrow biopsy was without evidence of leukemia. Involvement of the vulva, vaginal and adjacent cervical area only was confirmed. She received re-induction chemotherapy with clinical regression of both the vulvar, vaginal and the cervical masses; this was followed by radiation therapy to an extramedullary site. The correct diagnosis of myeloid sarcoma, particularly of an isolated mass in the genital area, is important because of its rarity and the need for appropriate institution of therapy.

Right heart thrombus-in-transit with pulmonary embolism in a patient with primary hypercoagulable state.

A 25 year-old female with a history of Caesarian section ten weeks ago presented with symptoms suggestive of pulmonary embolism. Transthoracic echocardiography revealed a free-floating large thrombus traversing the right atrial cavity. Transesophageal echocardiography confirmed the presence of an unattached thrombus that originated from the most proximal part of the inferior vena cava. Multi-slice computed tomography of the chest and abdomen revealed the thrombus to start from the intra-hepatic part of the inferior vena cava and extend through the right atrium. It also demonstrated multiple thrombi in the pulmonary vasculature, the largest being in the right main pulmonary artery and its lower lobe branch. The patient was triaged for surgical embolectomy under cardio-pulmonary bypass. Follow-up trans-thoracic and transesophageal echocardiography confirmed adequate removal of the thrombus. By genetic examination, she proved to have factor V 'Leiden' gene and two thrombophilia genes, all of which were positive in the heterozygous state. She had also a high serum homocysteine.

Pro-inflammatory cytokines and depression in patients with acute leukemia.

The prevalence of depression among patients diagnosed with cancer is higher than general population and is associated with faster tumor progression and shorter survival time. Cytokines whose primary function is to act as signaling molecules of the immune system have recently also been implicated in the pathogenesis of depression. The aim of present study was to investigate the relation between pro-infammatory cytokines [Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha)], depression and stressful life events in patients with acute leukemia. Twenty eight patients (18 males and 10 females) suffering from acute leukemia participated in this study. Their mean age was 33.3 +/- 12.1 years. They were subjected to psychiatric assessment using The Beck Depression Inventory (BDI), Holmes and Rahe Social Readjustment Scale, The Perceived Stress Scale (PSS) and The Brief Fatigue Inventory (BFI). Measurement of IL-6 and TNF-a genes expression in peripheral blood mononuclear cells was done using real-time PCR. Results revealed statistically significant elevation in the level of IL-6 gene expression, fatigue and perceived stress among depressed patients compared to none depressed group. The same results were obtained when comparing patients exposed to moderate or severe stressful life events compared to those exposed to none or mild stressful life events. Although, TNF-a gene expression was not associated with depression or stressful life events, it was associated with acute myeloblastic leukemia (AML). IL-6 gene expression was much higher among patients with AML than acute lymphoblastic leukemia (ALL), but the difference did not reach statistical significance. These findings support the hypothesis that IL-6 might be involved in the etiology and symptomatology of depression in cancer patients. The development of biologic therapies targeting IL-6 may raise the possibility of simultaneously countering the severe effects of depression.

Correlation of telomerase activity to apoptosis and survival in adult acute lymphoblastic leukemia: an Egyptian single-center study.

Telomerase is activated in most tumors, but suppressed in normal human somatic cells. Current evidence indicates that telomerase reactivation is a critical step in carcinogenesis, with a close relationship to apoptosis. The goal of this study was to investigate the levels and relationship of telomerase activity to apoptosis and its impact on the survival of Egyptian adult acute lymphoblastic leukemia patients. Telomerase activity was quantified by polymerase chain reaction (PCR) and detected by enzyme-linked immunosorbent assay (ELISA), while apoptosis was measured at the single-cell level by fluorescence in situ detection using flow cytometry in 15 control subjects and 40 acute lymphoblastic leukemia (ALL) patients at presentation. Telomerase activity in ALL patients was negatively correlated to apoptosis [percent and mean fluorescence intensity (MFI)] (p < 0.001 for percent and p < 0.001 for MFI) and to the 4-year survival rate (p < 0.05), to which apoptosis (percent and MFI) was consequently positively correlated (p < 0.001 for percent and p < 0.05 for MFI). For telomerase, the highest positive predictive value (PPV) for mortality (93.3%) was at a cut-off value of 13 amol/ml, while those for apoptosis (85% for percent of apoptotic cells and 90.9% for MFI) were at a cut-off of 8% and 0.19 MFI. This makes the measurement of telomerase activity in ALL patients a potential tool to predict disease with unfavorable outcome and a candidate tumor marker.