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.

The Role of Pre-bone Marrow Transplantation Pulmonary Function Test in Predicting Post-transplant Noninfectious Pulmonary Complications.

Background: Pulmonary function test (PFT) is used as a tool for pre-transplant risk assessment and as a predictor of post-transplant outcomes. As there are currently few studies that discuss the role of PFT in bone marrow transplantation (BMT) patients in Saudi settings, and as the number of transplant patients with benign and malignant conditions continues to increase, this study was conducted with the aim of assessing the local practice. Methods: This retrospective cohort study included all adult patients who underwent BMT at Princess Noorah Oncology Center, King Abdulaziz Medical City, Jeddah, between 2014 and 2020. The association between established patient-related risk factors and the incidence of pulmonary complications among autologous and allogeneic groups was assessed. Results: A total of 186 patients were included (autologous = 143; allogenic = 43), of which 115 (61.8%) were male. At the pre-BMT phase, about 30% of the patients had comorbidities and 51% had received two rounds of salvage chemotherapy, while 16.1% had received radiation therapy. In the autologous group, the only PFT parameter that was a significant predictor of post-BMT pulmonary complications was forced vital capacity <80% (P = 0.012), while in the allogenic group, no parameter was significantly associated with pulmonary complications. The patient-related factors that were associated with respiratory distress in the autologous group were lung involvement (P = 0.03) and pre-transplant radiation (P = 0.044). Conclusion: The findings of this study indicated that forced vital capacity <80% was a significant factor in predicting non-infectious complications in the autologous group. Furthermore, lung involvement and pre-transplant radiation were the patient-related factors associated with pulmonary complications.

Comparison of a modified pediatric protocol versus a hyper-CVAD protocol in adolescents and young adults with Philadelphia-negative acute lymphoblastic leukemia: A multicenter retrospective analysis.

BACKGROUND: The outcomes of Pediatric acute lymphoblastic leukemia (ALL) have improved dramatically whereas outcomes for ALL amongst adolescents and young adults (AYA) have lagged behind. The introduction of pediatric-like regimens to manage adult ALL has shown promising outcomes across several analyses. MATERIALS AND METHODS: In this analysis, we aimed to retrospectively compare the differences in outcomes among patients aged 14-40 years with Philadelphia-negative ALL treated with a Hyper-CVAD protocol versus a modified pediatric protocol. RESULTS: A total of 103 patients were identified with 58 (56.3%) in the modified ABFM group and 45 (43.7%) in the hyper-CVAD group. The median duration of follow-up for the cohort was 39 months (range 1-93). There were significantly lower rates of MRD persistence after consolidation (10.3% vs. 26.7%, P = 0.031) and transplantation (15.5% vs. 46.6%, P < 0.001) in the modified ABFM group. 5-year OS rates (83.9% vs. 65.3%, P = 0.036) and DFS rates (67.4% vs. 44%, P = 0.014) were higher in the modified ABFM groups. The incidence of grade 3 and 4 hepatotoxicity (24.1% vs. 13.3%, P < 0.001) and osteonecrosis (20.6% vs. 2.2%, P = 0.005) were higher in the modified ABFM group. CONCLUSION: Our analysis demonstrates that the use of a pediatric modified ABFM protocol demonstrated superior outcomes compared to the hyper-CVAD regimen in the treatment of Philadelphia-negative ALL amongst AYA patients. However, the modified ABFM protocol was associated with an increased risk of certain toxicities including high grade liver toxicity and osteonecrosis.

Outcomes of high­dose methotrexate for CNS prophylaxis in diffuse large B­cell lymphoma with an intermediate or high CNS­International Prognostic Index: A single­center retrospective cohort study.

Central nervous system (CNS) relapse in patients with diffuse large B-cell lymphoma (DLBCL) is rare (2-5% of cases), but is a devastating complication with a poor survival rate. The administration of high-dose methotrexate (HDMTX) for CNS prophylaxis in patients with DLBCL is controversial and variable in the literature. The present study aimed to evaluate the clinical outcomes of HDMTX CNS prophylaxis in patients with intermediate and high CNS-International Prognostic Index (IPI) DLBCL using real-world data. An observational retrospective cohort study was conducted of all patients with intermediate and high CNS-IPI DLBCL treated at Princess Noorah Oncology Center (King Abdulaziz Medical City, Jeddah, Saudi Arabia) between January 2010 and December 2020. Patients were treated with HDMTX either intravenously or intrathecally, according to the physician's evaluation of the patient. Data on patient clinical characteristics, CNS relapses, risk factors and survival rates were obtained from hospital records. Data were analyzed using Student's unpaired t-test and the χ2 test to compare the two subgroups, the Kaplan-Meier survival method with log-rank test to calculate and compare the survival rates, and regression analysis to determine the risk factors for CNS relapse and death. The study included 358 patients (n=32 with HDMTX CNS prophylaxis and n=326 without CNS prophylaxis). Patients in the CNS prophylaxis group had a significantly higher CNS relapse rate than those in the non-CNS prophylaxis group (12.5% vs. 1.8%; P=0.008). Patients who received CNS prophylaxis were younger and had an advanced stage of disease, with extranodal involvement and a high serum lactate dehydrogenase level at presentation. CNS prophylaxis was significantly associated with CNS relapse, while relapsed disease was associated with the risk of death (all P<0.05). In conclusion, the present study found that patients with intermediate and high CNS-IPI who received HDMTX CNS prophylaxis did not have fewer CNS relapses; however, those without CNS relapse had higher survival rates. In addition to CNS prophylaxis, Stage of DLBCL and IPI were significantly associated with CNS relapse. Future randomized control trials are needed to evaluate the efficacy of HDMTX CNS prophylaxis in patients with DLBCL.

Autologous peripheral blood stem cell mobilization and collection in patients with lymphoma and multiple myeloma: A single-center experience using the plerixa for pre-emptive approach.

OBJECTIVES: To review and assess the efficiency of pre-emptive plerixafor administration for poor mobilization (PM) and to review and assess mobilization efficiency (≥2×106 CD34+ cells/kg) in patients who received autologous stem cell transplantation for lymphoma and multiple myeloma (MM) at the Department of Adult Hematology/Blood Marrow Transplant, Princess Noorah Oncology Center, King Abdulaziz Medical City, Jeddah, Saudi Arabia, over the past 7 years. METHODS: This retrospective study evaluated all patients with MM and lymphoma undergoing peripheral blood stem cell mobilization and collection at our institution between February 2014 and August 2021. Plerixafor was administered pre-emptively by a plateau of <10 peripheral blood CD34+/µl after chemotherapy-based mobilization or CD34+ of <8/µL on day 4 after mobilization with G-CSF alone. Between peak CD34+ levels of 10-15/µl, plerixafor will be used at the discretion of the treating physician. RESULTS: In total, 215 patients were enrolled. Among them, 80% had peak CD34+ level ≥20/µL, 11% had clear poor mobilization (peak CD34+ levels <10/µL), and 9% had borderline PM (CD34+ between 10-19/µL). Plerixafor was administered pre-emptively in 13% of the patients and 75% of patients with borderline PM were collected without plerixafor, suggesting that plerixafor is not needed if CD34+ >15/µL on the anticipated collection day. Mobilization failed in only one patient (<1%). CONCLUSION: Our data showed that with plerixafor pre-emptive administration, the primary endpoint was achieved for most patients identified with PM, preventing the need for a second mobilization attempt.

Optimal Management of Acute Lymphoblastic Leukemia (ALL) in Adult Patients During the Novel Coronavirus Disease 2019 (COVID-19) Pandemic.

The outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency of major international concern. In December 2019, an outbreak of atypical pneumonia known as COVID-19 was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), is characterized by rapid human-to-human transmission. Acute lymphoblastic leukemia (ALL) patients are often in need for intensive chemotherapy to induce remission that will be complicated with prolonged period of cytopenias. They are often recalled to the hospital for treatment and disease surveillance. These patients may be immunocompromised due to the underlying malignancy or anti-cancer therapy. ALL patients are at higher risk of developing life-threatening infections. Several factors increase the risk of infection and the presence of multiple risk factors in the same patient is common. Cancer patients had an estimated 2-fold increased risk of contracting SARS-CoV-2 than the general population. With the World Health Organization declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such pandemic on ALL patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the optimal management of ALL patients in any infectious pandemic. In this review, we will address the potential challenges associated with managing ALL patients during the COVID-19 infection pandemic with suggestions of some practical approaches, focusing on screening asymptomatic ALL patients, diagnostic and response evaluation and choice of chemotherapy in different scenarios and setting and use of hematopoietic stem cell transplantation (HSCT).