Chemotherapy versus Hypomethylating Agents for the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome after Allogeneic Stem Cell Transplant.

Allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). For patients with relapsed disease after transplantation, intensive chemotherapy followed by donor lymphocyte infusion (DLI) or a second allo-SCT may result in a durable response in some patients. High-intensity chemotherapy and less aggressive therapy with hypomethylating agents (HAs) with and without DLI are often used for relapse after allo-SCT. Here we compared the treatment outcomes of intensive chemotherapy with that of HAs in relapsed AML and MDS after allo-SCT. Patients who had received a second SCT within 90 days of the relapse date were excluded. The primary endpoints were overall response rate (ORR) and overall survival (OS). Secondary endpoints were complete remission (CR) rate and progression-free survival (PFS). One hundred patients were included: 73 patients received chemotherapy and 27 patients received an HA. Fifty-six percent of patients in the chemotherapy group and 33% of patients in the HA group received at least 1 DLI after treatment. Treatment with chemotherapy resulted in a higher ORR (51% versus 19%, P = .004) and a higher CR rate (40% versus 7%, P = .002). The median OS (6 versus 3.9 months, P = .01) and PFS (4.9 versus 3.8 months, P = .02) were longer in the chemotherapy group. Similar benefit of chemotherapy over HAs was maintained in all treatment outcomes after controlling for the use of DLI. The use of chemotherapy followed by DLI offered the greatest benefit (ORR, 68%; CR, 59%, 1-year OS, 44%; and median OS, 9.8 months). In conclusion, in our hands, with limited numbers, the use of more conventional salvage chemotherapy, with DLI when possible, for the treatment of relapsed AML and MDS after allo-SCT is associated with better outcomes than nonchemotherapy (HA) options.

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..

Primary Diffuse Large B-cell Lymphoma involving the Mandible.

Lymphomas of the oral cavity are rare and typically present as intraosseous lesions that are most commonly diffuse large B-cell type. Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma histologically characterized by diffuse proliferation of large neoplastic B-lymphoid cells with a nuclear size equal to or exceeding normal histiocytic nuclei. A case of DLBCL of the mandible in an 18 years old male patient is presented. This report discusses this rare malignancy, including clinical presentation, histopathologic features, immunologic profile, treatment and prognosis. Though lymphoma of mandible is rare, it must be considered in differential diagnosis of swellings arising in the region.

A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia.

The interaction of acute myeloid leukemia (AML) blasts with the leukemic microenvironment is postulated to be an important mediator of resistance to chemotherapy and disease relapse. We hypothesized that inhibition of the CXCR4/CXCL12 axis by the small molecule inhibitor, plerixafor, would disrupt the interaction of leukemic blasts with the environment and increase the sensitivity of AML blasts to chemotherapy. In this phase 1/2 study, 52 patients with relapsed or refractory AML were treated with plerixafor in combination with mitoxantrone, etoposide, and cytarabine. In phase 1, plerixafor was escalated to a maximum of 0.24 mg/kg/d without any dose-limiting toxicities. In phase 2, 46 patients were treated with plerixafor 0.24 mg/kg/d in combination with chemotherapy with an overall complete remission and complete remission with incomplete blood count recovery rate (CR + CRi) of 46%. Correlative studies demonstrated a 2-fold mobilization in leukemic blasts into the peripheral circulation. No evidence of symptomatic hyperleukocytosis or delayed count recovery was observed with the addition of plerixafor. We conclude that the addition of plerixafor to cytotoxic chemotherapy is feasible in AML, and results in encouraging rates of remission with correlative studies demonstrating in vivo evidence of disruption of the CXCR4/CXCL12 axis.

Management of adult acute lymphoblastic leukemia in the Gulf Cooperation Council (GCC) countries: A consensus report from the GCC Adult ALL Working Group.

Leukemia burden is growing in the Gulf Council Cooperation (GCC) countries. Nonetheless, there is no unified protocol for managing adult acute lymphoblastic leukemia (ALL) patients in the GCC-countries. Therefore, the GCC Adult-ALL Treaters working group developed this consensus to address the adult-ALL treatment protocols in the GCC-countries and related toxicities' management. Besides, the consensus aimed to highlight the current unmet needs and treatment gaps and provide recommendations to optimize adult-ALL care and patient-centered communication. A three-step modified Delphi method to develop evidence-based recommendations through two-voting rounds and in-between virtual meetings are used in the manuscript development. A 12 experts' panel from five GCC-countries and two international experts were invited to participate in this consensus. This consensus consisted of 35-statements that highlighted the experts' recommendations to optimize ALL adults' care in the first line setting and manage pediatric or pediatric-inspired regimens-related toxicities. Besides, guidance was provided for future research direction and improve patient-centered communication. In conclusion, the adult-ALL management landscape is evolving, and the current evidence highlights better response and survival outcomes with pediatric or pediatric-inspired regiments. Therefore, protocols are needed to optimize the adult-ALL management in the GCC and tailored clinical-trials findings according to the GCC patients' characteristics and local-healthcare infrastructure.

Real-World Registry on the Pharmacotherapy of Multiple Myeloma and Associated Renal and Pulmonary Impairments in the Greater Gulf Region: Protocol for a Retrospective Real-World Data Study.

BACKGROUND: Multiple myeloma (MM) is the second-most common cancer among hematological malignancies. Patients with active disease may experience several comorbidities, including renal insufficiency and asthma, which may lead to treatment failure. The treatment of relapsed or refractory MM (RRMM) has been associated with multiple factors, causing a decline in progression-free survival as well as overall survival with subsequent lines of therapy. Data about the characteristics of this group of patients in the Greater Gulf region are lacking. OBJECTIVE: The primary objective of this study is to describe the disease characteristics and various treatment approaches or regimens used in the management of patients with RRMM in the Greater Gulf region. METHODS: We will conduct a regional, retrospective study collecting real-world and epidemiological data on patients with MM in countries of the Greater Gulf region. Medical records will be used to obtain the required data. Around 150 to 170 patients' records are planned to be retrospectively reviewed over 6 months without any cross-sectional or prospective intervention. Cases will be collected from Saudi Arabia, the United Arab Emirates, Kuwait, Oman, and Qatar. Descriptive as well as analytical statistics will be performed on the extracted data. The calculated sample size will allow us to estimate the percentages of RRMM cases with acceptable precision while complying with the challenges in light of data scarcity. We will obtain a comprehensive description of the demographic profile of patients with MM; treatment outcomes; the proportion of patients with MM with renal impairment and asthma, chronic obstructive pulmonary disease, or both at the time of diagnosis and any subsequent point; and data related to treatment lines, regimens, and MM-associated morbidities. RESULTS: Patient medical records were reviewed between June 2022 and January 2023 for eligibility and data extraction. A total of 148 patients were eligible for study inclusion, of whom 64.2% (n=95) were male and 35.8% (n=53) were female. The study is currently in its final stages of data analysis. The final manuscript is expected to be published in 2024. CONCLUSIONS: Although MM is a predominant hematological disease, data on its prevalence and patients' characteristics in the Greater Gulf region are scarce. Therefore, this study will give us real-world insights into disease characteristics and various management approaches of patients with MM in the Greater Gulf region. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49861.

The Successful Implementation of a Modified Pediatric Acute Lymphoblastic Leukemia Protocol to Treat an Elderly Patient With T-cell Lymphoblastic Leukemia: A Case Report.

Acute lymphoblastic leukemia (ALL) is a group of hematological malignancies most commonly seen in pediatrics. The disease process localizes in lymphoid organs, the central nervous system, the mediastinum, and bone marrow (BM). The clinical features of T-cell acute lymphoblastic leukemia (T-ALL) in adults include evidence of generalized lymphadenopathy, hepatosplenomegaly, immunosuppression, and hypercalcemia. There is limited research on the efficacy of using modified pediatric treatment regimens in the elderly over the age of 60 with ALL; this case report aims to illustrate the successful treatment of a 67-year-old male patient diagnosed with T-ALL, using a modified Children's Oncology Group (COG) protocol. Through this, it has been shown to be an effective, safe, and efficacious treatment option for our patient.

Favorable outcome of PML-RARα short isoform and FLT3-ITD mutation in a patient with several adverse prognostic markers: A case report.

Key Clinical Message: Complete molecular remission in a "variant APL" patient with short isoform of PML-RARα and FLT3-ITD mutation was achieved in response to ATRA and ATO plus IDA instead of standard treatment protocol. The use of FLT3 inhibitor in APL induction management is implicated to prevent differentiation syndrome and coagulopathy experienced in in patients with FLT3-ITD. Abstract: FLT3-ITD mutations are the most common activating mutations in FLT3 gene, occurring in about 12 to 38% of acute promyelocytic leukemia cases, and are mainly associated with high white blood cell counts and poor clinical outcomes. Here, we present a case of APL variant with adverse prognostic features who showed short isoform [bcr3] of PML-RARα and FLT3-ITD mutation at diagnosis. The patient received all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) plus idarubicin (IDA) instead of standard treatment protocol, and achieved a complete morphological, cytogenetic and molecular response. However, the patient experienced differentiation syndrome, and coagulopathy that was subsequently resolved by continuous oxygen therapy, dexamethasone, and enoxaparin. The use of FLT3 inhibitor in APL induction management is implicated to prevent differentiation syndrome and coagulopathy in patients with FLT3-ITD mutation.

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.

Durable remission of a patient with primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma.

Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (CD8+ PCAETL) is a rare disease characterized by aggressive clinical course and short survival. All available data are extracted from case reports and case series. The outcome is dismal and only two reported cases were cured after several lines of therapies including stem cell transplant. We herein present the case of a patient with CD8+ PCAETL who presented with rapidly progressive skin lesions and systemic symptoms. He was treated with aggressive multiagent chemotherapy comprising cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD). The treatment resulted in durable complete remission with no evidence of disease recurrence after 58 months of follow-up. This is the first reported case of durable remission after first-line treatment.

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.

Clinical course and outcomes of COVID-19 in hematopoietic cell transplant patients, a regional report from the Middle East.

The coronavirus disease-2019 (COVID-19) caused by SARS Coronavirus 2 (SARS-CoV-2) is a potentially lethal infection. Cancer patients, and specifically hematopoietic cell transplant (HCT) recipients are severely immunocompromised and may be at a higher risk of a complicated course with this infection. We aimed to study the COVID-19 outcomes and severity in post HCT patients. We retrospectively reviewed post-HCT patients diagnosed with COVID-19 between March 15, 2020, and December 1, 2020 at 10 transplant centers across the Middle East. We identified 91 patients with confirmed SARS-CoV-2 infection across 10 transplant centers. The median age upon presentation with COVID-19 was 35. Fifty two patients were post allo-HCT while the remaining 39 patients were post auto-HCT. The median time from transplant was 14.9 months. Mortality rate was 4.4%. Hospital admission rate was 53%. ICU admission rate was 14%. Mechanical ventilation rate was 10%. Oxygen supplementation rate was 18%. Time from HCT to COVID-19 >6 months was associated with lower admission rates and lower rates of the "severity" composite endpoint. Antibody responses was seen 67% of evaluable patients. In this series of HCT recipients, we report overall favorable clinical outcomes for patients with COVID-19 and provide preliminary insights into the clinical course of this disease in this specific population.

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.

Saudi Lymphoma Group's Clinical Practice Guidelines for Diagnosis, Management and Follow-up of Patients with Various Types of Lymphoma during the Coronavirus Disease 2019 Pandemic.

The Saudi Lymphoma Group had previously published recommendations on the management of the major subtypes of lymphoma. However, the effect the currently ongoing coronavirus disease 2019 (COVID-19) pandemic has on the management of patients with lymphoma has been paramount. Therefore, the Saudi Lymphoma Group has decided to provide clinical practice guidelines for the diagnosis, management and follow-up of patients with various types of lymphoma during the COVID-19 pandemic.

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.

Systemic Lupus Erythematosus Presenting as Hematoma of the Hand Due to Acquired Inhibitors to Factor VIII: Early and Prolonged Remission Achieved with Upfront Rituximab.

Acquired hemophilia is a rare autoimmune disorder that is a result of antibodies against clotting factor VIII and it presents with excessive or prolonged bleeding, often into the muscles. Thrombotic phenomena with lupus anticoagulant are common in patients with systemic lupus erythematosus (SLE). We report a rare case of a young female with no significant past medical history presenting with hematoma of the hand who was later on found to have acquired hemophilia, SLE with antiphospholipid antibodies (APLA). She was successfully treated with upfront rituximab and prednisolone leading to early and prolonged remission. No increased incidence of infections was noted. Upfront rituximab appears to be a safe and effective option in the management of such patients when compared to use of cytotoxic agents such as cyclophosphamide; however, further data from randomized studies is needed. Neutropenia and acquired hemophilia should also be considered to be listed under hematological manifestations of SLE diagnostic criteria, as they are not uncommon in such patients.

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.