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.

Lenalidomide-Induced Diffuse Alveolar Hemorrhage in Patient With Multiple Myeloma.

We present a case of multiple myeloma that was treated with a regimen that included lenalidomide. Lenalidomide, a thalidomide analog, is an immunomodulatory drug created synthetically by changing the chemical makeup of thalidomide to increase efficacy and lessen negative effects. It has been authorized for the treatment of relapsed or resistant multiple myeloma. In the case discussed in this report, the patient's lenalidomide dosage was changed to account for her renal impairment. Regardless of this adjustment of the dose, the patient presented with lung infiltrates, hemoptysis, and fever. Unfortunately, she was diagnosed with diffuse alveolar hemorrhage (DAH) secondary to lenalidomide after excluding other causes of hemoptysis. To the best of our knowledge, we believe this is the first case of DAH reported with lenalidomide in Saudi Arabia, which also discusses the possible therapeutic options for such presentations.

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.

A 68-Year-Old Man with a Cytogenetic Diagnosis of Chronic Myeloid Leukemia and Bone Marrow Findings of Philadelphia Chromosome Translocation Between the Long Arm of Chromosomes 9 and 22, Leading to the BCR-ABL1 Fusion Gene and V617F Mutation in the JAK2 Gene.

BACKGROUND Breakpoint cluster region (BCR)-Abelson murine leukemia (ABL1) and Janus Kinase-2 (JAK2) mutations have been thought to be mutually exclusive in myeloproliferative neoplasms (MNPs), but recent data suggest that they can occur together. CASE REPORT A 68-year-old man was referred to the hematology clinic because of an elevated white blood cell count. His medical history included type II diabetes mellitus, hypertension, and retinal hemorrhage. Fluorescence in situ hybridization analysis of the bone marrow was positive for BCR-ABL1 in 66/100 cells. Conventional cytogenetics was positive for the Philadelphia chromosome in 16/20 counted cells. The percentage of BCR-ABL1 was 12%. Considering the patient's age and medical comorbidities, he was started on imatinib 400 mg once daily. Further tests showed JAK2 V617F mutation positivity and absence of acquired von Willebrand disease. He was then started on aspirin 81 mg and hydroxyurea 500 mg once daily, which was later increased to 1000 mg daily. The patient achieved a major molecular response after 6 months of treatment, with undetectable BCR-ABL1 levels. CONCLUSIONS BCR-ABL1 and JAK2 mutations can co-existence in MNPs. Physicians must suspect the presence of one of the MPNs in chronic myeloid leukemia (CML) patients with persistent or increased thrombocytosis, an atypical course of the disease, or hematological abnormalities despite evidence of response or remission of CML. Therefore, testing for JAK2 should be performed accordingly. Combining cytoreductive therapy with tyrosine kinase inhibitors (TKIs) is a therapeutic option when both mutations are present, and TKI alone is not sufficient to control peripheral blood cell counts.

Comparison of Biosimilar Filgrastim with Innovator Fligrastim for Peripheral Blood Stem Cells Mobilization, Collection of CD34+ Stem Cells, and Engraftment in Patients Undergoing Autologous and Allogeneic Stem Cell Transplantation: A Single-Center Experience.

BACKGROUND In the Middle East, there is lack of data on peripheral blood CD34+stem cells mobilization by using biosimilar filgrastim. We have been using both Neupogen and a biosimilar G-CSF) Zarzio® (as a mobilizing agent since February 2014 for both allogenic and autologous stem cell transplantations. MATERIAL AND METHODS This was a single-center retrospective study. All patients and healthy donors who received either the biosimilar G-CSF (Zarzio®) or original G-CSF (Neupogen®) for mobilization of CD34+ stem cells were included in the study. The primary goal was to determine and compare the rate of successful harvest and amount of CD34+ stem cells collected in either adult cancer patients or healthy donors between Zarzio® and Neupogen® groups. RESULTS A total of 114 patients, including 97 cancer patients and 17 healthy donors, underwent successful CD34+ stem cell mobilization using G-CSF with chemotherapy (35 with Zarzio® +chemotherapy, 39 with Neupogen® +chemotherapy) or G-CSF as monotherapy (14 with Zarzio®, 9 with Neupogen®) in autologous transplantation. In an allogeneic stem cell transplantation, successful harvest was achieved by using G-CSF monotherapy (8 with Zarzio®, 9 with Neupogen®). There was no difference between Zarzio® and Neupogen® in the amount of CD34+ stem cells collected at leukapheresis. There was no difference with regards to secondary outcomes between the 2 groups. CONCLUSIONS Our study showed that biosimilar G-CSF (Zarzio®) has comparable efficacy to the original G-CSF (Neupogen®) when used for mobilization in both autologous and allogenic stem cell transplantation and was associated with significant cost saving.

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.

Early infection in post-autologous hematopoietic stem cell transplant patients: Princess Noorah Oncology Center experience.

OBJECTIVES: To assess local epidemiology and risk factors for bacterial, fungal, and viral infections among the autologous bone marrow transplant population. METHODS: This study is a retrospective correlational cohort design comprising 150 adult patients who underwent autologous transplants at Princess Noorah Oncology Center, Jeddah, Saudi Arabia between 2014 and 2020. RESULTS: The study findings indicate that bacterial infection prevalence differed significantly across the different disease status pre-salvage as patients with the relapsed disease were more likely to have bacterial infections. The median of engraftment days differed significantly between those who had a bacterial infection and those who did not. Interestingly, previous pneumonia infection had a positive relationship with the number of hospital stays. CONCLUSIONS: Bacterial infections are the dominant type of infection among the autologous patient population. The research reflects authentic practice and reports unique characteristics of autologous transplant patients in terms of the prevalence and types of infection these patients experience.

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.

Salvage chemotherapy and autologous stem cell transplantation for transformed indolent lymphoma: a subset analysis of NCIC CTG LY12.

The treatment of transformed indolent lymphoma (TRIL) often includes salvage chemotherapy (SC) and autologous stem cell transplant (ASCT). NCIC CTG LY12 is a randomized phase 3 trial comparing gemcitabine, dexamethasone, and cisplatin (GDP) with dexamethasone, cytarabine, and cisplatin (DHAP) before ASCT. This analysis compares the results of SC and ASCT for TRIL with de novo diffuse large B-cell lymphoma (DLBCL). Six-hundred nineteen patients with relapsed/refractory aggressive non-Hodgkin lymphoma were randomized to GDP or DHAP; 87 patients (14%) had TRIL and 429 (69%) had DLBCL. The response rate to SC was 47% in TRIL and 45% in DL (P = .81). Transplantation rates were similar: TRIL 53% and DL 52% (P = 1.0). With a median follow-up of 53 months, 4 year overall survival was 39% for TRIL and 41% for DL (P = .78); 4 year event-free survival (EFS) was 27% for TRIL and 27% for DL (P = .83). Post-ASCT, 4-year EFS was 45% for TRIL and 46% for DL. Histology (TRIL or DL) was not a predictor of any outcome in multivariate models. Patients with relapsed or refractory TRIL and DLBCL have similar outcomes with SC and ASCT; this therapy should be considered the standard of care for patients with TRIL who have received prior systemic chemotherapy. NCIC CTG LY12 is registered at ClinicalTrials.gov as #NCT00078949.