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.

Upfront Alternative Donor Transplant versus Immunosuppressive Therapy in Patients with Severe Aplastic Anemia Who Lack a Fully HLA-Matched Related Donor: Systematic Review and Meta-Analysis of Retrospective Studies, on Behalf of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation.

Idiopathic aplastic anemia is a rare and life-threatening disorder, and hematopoietic stem cell transplantation (HSCT) from a matched sibling donor (MSD) is the standard treatment strategy for young patients. Alternative donor transplantation (ADT) from a matched unrelated donor or an HLA haploidentical donor is not commonly used in the frontline setting. This systematic review/meta-analysis was conducted to compare ADT as an upfront, rather than delayed, treatment strategy in the absence of an MSD to immunosuppressive therapy (IST) in severe aplastic anemia (SAA). We searched PubMed/MEDLINE and Embase (1998 to 2019) for studies that compared the outcomes of ADT with IST as upfront therapy in patients with SAA. We included studies with 5 patients or more in each arm. Studies that included patients with inherited forms of bone marrow failure syndromes were excluded. The primary outcome was the 5-year overall survival (OS) rate. Five studies met the inclusion criteria and were included in this meta-analysis. The pooled 5-year odds ratio (OR) for OS was statistically significant at 0.44 (95% confidence interval [CI], 0.23 to 0.85) in favor of upfront ADT. In addition, survival was compared between upfront ADT versus salvage ADT in 6 studies. The pooled 5-year OR for OS was statistically significant at 0.31 (95% CI, 0.15 to 0.64) in favor of upfront ADT. Although this analysis has some limitations, including the retrospective nature of the included studies, the lack of ethnic diversity, the predominantly pediatric population, and the relatively suboptimal IST regimen used in some of the studies, it indicates that upfront ADT is a potential alternative treatment option in young and pediatric SAA patients who lack an HLA identical sibling donor, particularly when optimal IST is not available. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Role of 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography Imaging in the Prediction of Prognosis in Patients With Indolent Lymphoma: Prospective Study.

BACKGROUND: The role of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in indolent lymphoma has been minimally studied. OBJECTIVE: This study aims to assess the value of FDG-PET/CT in predicting the prognosis of indolent lymphoma. METHODS: We prospectively recruited 42 patients with indolent lymphoma. A total of 2 patients were excluded, and 40 underwent baseline PET/CT and follow-up at various time points. A total of 9 patients were observed only, 7 received 4 doses of rituximab alone, and 24 received chemoimmunotherapy. Metabolic response on follow-up PET/CT was assessed using the maximum standardized uptake value (SUVmax) and Deauville criteria (DC). We aimed to obtain the best SUVmax and DC to predict optimal survival rates, risk stratification, and optimize therapeutic strategies. The mean follow-up from the initial diagnosis was 33.83 months. RESULTS: SUVmax <4.35 at interim PET/CT provided the best discrimination, with a progression-free survival (PFS) of 100% and a median survival time of 106.67 months compared with SUVmax ≥4.35 (P=.04), which had a PFS of 43.8% and a median survival time of 50.17 months. This cutoff was also valuable in predicting overall survival at baseline, that is, 100% overall survival with baseline SUVmax <4.35, versus 58.4% for SUVmax ≥4.35 (P=.13). The overall survival of patients with a baseline DC score <3.0 was 100%, with a median overall survival of 106.67 months. CONCLUSIONS: We demonstrated the utility of PET/CT in indolent lymphomas. SUVmax (<4.35 vs ≥4.35) on interim PET/CT performed best in predicting PFS.

Safety and Efficacy of Convalescent Plasma for Severe COVID-19: Interim Report of a Multicenter Phase II Study from Saudi Arabia.

OBJECTIVE: To present the interim findings from a national study investigating the safety and efficacy of convalescent plasma (CP) containing detectable IgG antibodies as a treatment strategy for severe coronavirus disease 2019 (COVID-19). TRIAL DESIGN AND PARTICIPANTS: An open label, two-arm, phase-II clinical trial conducted across 22 hospitals from Saudi Arabia. The intervention group included 40 adults (aged ≥18 years) with confirmed severe COVID-19 and the control group included 124 patients matched using propensity score for age, gender, intubation status, and history of diabetes and/or hypertension. Intervention group included those (a) with severe symptoms (dyspnea; respiratory rate, ≥30/min; SpO2, ≤93%, PaO2/FiO2 ratio, <300; and/or lung infiltrates >50% within 24-48 h), (b) requiring intensive care unit (ICU) care or (c) experiencing life-threatening conditions. The control group included confirmed severe COVID-19 patients of similar characteristics who did not consent for CP infusion or were not able to receive CP due to its nonavailability. INTERVENTIONS: The intervention group participants were infused 300 ml (200-400 ml/treatment dose) CP at least once, and if required, daily for up to 5 sessions, along with receiving the best standard of care. The control group only received the best standard of care. OUTCOMES: The primary endpoints were safety and ICU length of stay (LOS). The secondary endpoints included 30-day mortality, days on mechanical ventilation and days to clinical recovery. RESULTS: CP transfusion did not result in any adverse effects. There was no difference in the ICU LOS (median 8 days in both groups). The mortality risk was lower in the CP group: 13% absolute risk reduction (P = 0.147), hazard ratio (95% confidence interval): 0.554 (0.299-1.027; P = 0.061) by log-rank test. There was no significant difference in the days on mechanical ventilation and days to clinical recovery. CONCLUSION: CP containing detectable antibodies is a safe strategy and may result in a decrease in mortality in patients with severe COVID-19. The results of the completed trial with a larger study sample would provide more clarity if this difference in mortality is significant. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04347681; Saudi Clinical Trials Registry No.: 20041102.

Prolonged Survival of a Patient with Chronic Myeloid Leukemia in Accelerated Phase with Recurrent Isolated Central Nervous System Blast Crisis.

BACKGROUND Chronic myeloid leukemia (CML) is usually a tri-phasic myeloproliferative neoplasm, characterized by the presence of the BCR-ABL1 fusion gene, derived from a balanced translocation, t(9;22)(q34;q11). BCR-ABL tyrosine kinase inhibitors (TKI) are used to treat patients with CML. The addition of pegylated interferon-alpha2b to imatinib or dasatinib results in promising deep molecular responses. Because imatinib shows poor penetration into the central nervous system (CNS), the CNS may become a sanctuary site in patients on prolonged imatinib therapy for CML. It is extremely rare for the blast phase in patients with chronic phase CML to affect the CNS without concomitant bone marrow involvement. CASE REPORT This report describes a 57-year-old woman who was diagnosed with accelerated phase (AP) CML and failed high dose imatinib therapy. Despite achieving an excellent molecular response to dasatinib in 6 months, she developed recurrent isolated CNS blast crisis. Survival was prolonged after treatment with intrathecal chemotherapy and whole-brain radiation therapy combined with dasatinib. After achieving long and deep molecular remission with dasatinib and a few months of pegylated interferon-alpha2a, she lived for 18 months in treatment-free-remission (TFR). At age 65 years, she died of progressive rectal carcinoma with septic shock, cancer-related venous thromboembolism, and a possible autoimmune disorder. CONCLUSIONS This patient with accelerated phase CML and 2 isolated CNS blast crises died in TFR 8.5 years after her initial diagnosis and 7.5 years after her first isolated CNS blast crisis. Survival resulted from tailoring of therapies around her comorbidities.

Safety and Efficacy of Convalescent Plasma to Treat Severe COVID-19: Protocol for the Saudi Collaborative Multicenter Phase II Study.

BACKGROUND: The COVID-19 pandemic is expected to cause significant morbidity and mortality. The development of an effective vaccine will take several months to become available, and its affordability is unpredictable. Transfusion of convalescent plasma (CP) may provide passive immunity. Based on initial data from China, a group of hematologists, infectious disease specialists, and intensivists drafted this protocol in March 2020. OBJECTIVE: The aim of this study is to test the feasibility, safety, and efficacy of CP in treating patients with COVID-19 across Saudi Arabia. METHODS: Eligible patients with COVID-19 will be recruited for CP infusion according to the inclusion criteria. As COVID-19 has proven to be a moving target as far as its management is concerned, we will use current definitions according to the Ministry of Health (MOH) guidelines for diagnosis, treatment, and recovery. All CP recipients will receive supportive management including all available recommended therapies according to the available MOH guidelines. Eligible CP donors will be patients with COVID-19 who have fully recovered from their disease according to MOH recovery criteria as detailed in the inclusion criteria. CP donors have to qualify as blood donors according to MOH regulations except for the history of COVID-19 in the recent past. We will also test the CP donors for the presence of SARS-CoV-2 antibodies by a rapid test, and aliquots will be archived for future antibody titration. Due to the perceived benefit of CP, randomization was not considered. However, we will compare the outcome of the cohort treated with CP with those who did not receive CP due to a lack of consent or lack of availability. In this national collaborative study, there is a likelihood of not finding exactly matched control group patients. Hence, we plan to perform a propensity score matching of the CP recipients with the comparator group patients for the major characteristics. We plan to collect demographic, clinical, and laboratory characteristics of both groups and compare the outcomes. A total sample size of 575 patients, 115 CP recipients and 460 matched controls (1:4 ratio), will be sufficient to detect a clinically important hospital stay and 30-day mortality difference between the two groups with 80% power and a 5% level of significance. RESULTS: At present, patient recruitment is still ongoing, and the interim analysis of the first 40 patients will be shared soon. CONCLUSIONS: In this paper, we present a protocol for a national collaborative multicenter phase II study in Saudi Arabia for assessing the feasibility, safety, and potential efficacy of CP in treating patients with severe COVID-19. We plan to publish an interim report of the first 40 CP recipients and their matched comparators soon. TRIAL REGISTRATION: ClinicalTrials.gov NCT04347681; https://clinicaltrials.gov/ct2/show/NCT04347681. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/23543.

COVID-19 and Palliative Care Services: Comparative Patterns of Inpatient, Outpatient, and Consultation Services in a Tertiary Care Center in Riyadh.

Introduction The coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the 21st century. The World Health Organization declared the COVID-19 outbreak as a pandemic on March 11, 2020. Lockdowns were imposed in multiple countries affecting patient flow in hospitals. Methods This is a retrospective study conducted at King Fahad Medical City (KFMC), a tertiary care hospital in Riyadh, Saudi Arabia, which examined the differences in palliative care services during the initial four months of the COVID-19 pandemic compared to the respective four months in 2019 (March, April, May, June). Results A total of 319 patients were seen at the palliative care department from March to June 2020 during the COVID-19 pandemic (119 inpatient, 200 outpatient), compared to 346 patients seen during the corresponding months in 2019 (97 inpatient, 249 outpatient). Our main findings included more patients being discharged home, lesser transfers, shorter hospital length of stay, lesser imminent death protocols, and a higher palliative performance score (PPS) during the COVID-19 pandemic. Although there were more cancelations by the hospital for the outpatient department, a virtual clinic was started, and 84 patients were effectively seen. Around 87% of patients were fully satisfied (5/5) with the services provided by the virtual clinic. There were no positive COVID-19 cases in our healthcare workers in the palliative care department due to the high standard precautions applied at KFMC. Family meetings as well as administrative and academic meetings have been efficiently held virtually and may possibly become the standard of practice. Conclusion Palliative care services were successfully maintained during the COVID-19 pandemic at KFMC.

The use of 5-azacytidine in pregnant patient with Acute Myeloid Leukemia (AML): a case report.

BACKGROUND: The management of Acute Myeloid Leukemia (AML) during pregnancy remains challenging as both the maternal and fetal outcomes should be considered. Several reports suggested that chemotherapy can be administered safely during the second and third trimester of pregnancy. However, the use of 5-azacytidine presents limitation due to lack of data. CASE PRESENTATION: A 28-years-old woman in the 26th week of gestation diagnosed with FLT3/ITD-mutated AML, complete remission was induced by Daunorubicin and Cytarabine, and subsequently with 5-azacytidine (75 mg/m2 daily for 7 days) with no fetal hematological or toxicity issues. Fetal ultrasound showed no aberrant morphology. Fetal size below the 5th percentile with normal umbilical artery dopplers, normal middle cerebral artery dopplers and ductus venosus doppler. Three weeks post 5-azacytidine, the team determined the most appropriate time for delivery after balancing the risks of prematurity and prevention of disease relapse since patient in hematological remission. The patient underwent elective lower segment caesarian section and had a baby girl delivered at 35 weeks of gestation weighing 1670 g without apparent anomalies. CONCLUSION: Treatment using 5-azacytadine during last trimester of pregnancy resulted in no major fetal and maternal complications. These findings concluded that 5-azacytadine during the third trimester of pregnancy seems to be safe however, potential risks of this agent should be considered.

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.

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..

Lymphoproliferative Disorders in Patients with Chronic Myeloid Leukemia: A Single-Center Case Series.

Lymphoproliferative disorders presenting simultaneously with or subsequent to the occurrence of chronic myeloid leukemia (CML) have rarely been reported. Herein, we report 8 cases of a variety of lymphoproliferative conditions associated with CML at different times during the course of the disease. All 8 patients were treated with tyrosine kinase inhibitors at some point during the course of their illness. The literature regarding the uncommon association of these apparently unrelated disorders is reviewed as well as the possible underlying mechanisms that could be associated with this phenomenon.

Imatinib-induced gastric antral vascular ectasia in a patient with chronic myeloid leukemia.

KEY CLINICAL MESSAGE: Gastric antral vascular ectasia (GAVE) has been reported very rarely in imatinib-treated gastrointestinal stromal tumor (GIST) and scleroderma/pulmonary hypertension patients. We present the first report of a case of GAVE in a chronic myeloid leukemia (CML) patient after treatment with imatinib. This diagnosis should be considered in CML patients with upper gastrointestinal symptoms and anemia.