Immune reconstitution and survival, following hematopoietic stem cell transplantation in Omani patients with inborn errors of immunity.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for certain inborn errors of immunity. METHODS: A 17-year retrospective cohort study was conducted on 40 immunodeficient patients who underwent HSCT. RESULTS: The median age at transplant was 11.0 months (4.6-61.0). Donors were primarily matched sibling donors (60%). 90% and 85% of patients received conditioning and graft-versus-host disease (GVHD) prophylaxis, respectively. The mean donor chimerism at the last follow-up was 88.6% ± 17.9% (40-100). Median serum immunoglobulin (Ig) G level, CD4+ T-cell count, and CD19+ B-cell count were 11.7 g/L (9.2-13.6), 0.9 × 109/L 0.6-1.2), and 0.5 × 109/L (0.2-0.7), respectively. 29 patients (72.5%) received intravenous immunoglobulins (IVIG) therapy, with a median duration of 10.0 months (4.0-14.0). The median post-transplant follow-up was 6.5 years (IQR:1.4-11.5). The 10-year overall probability of survival is 84.3%. CONCLUSION: Monitoring IRC is important in ensuring adequate disease-free survival.

Comparison of Noninvasive Mechanical Ventilation With High-Flow Nasal Cannula, Face-Mask, and Helmet in Hypoxemic Respiratory Failure in Patients With COVID-19: A Randomized Controlled Trial.

OBJECTIVES: For COVID-19-related respiratory failure, noninvasive respiratory assistance via a high-flow nasal cannula (HFNC), helmet, and face-mask noninvasive ventilation is used. However, which of these options is most effective is yet to be determined. This study aimed to compare the three techniques of noninvasive respiratory support and to determine the superior technique. DESIGN: A randomized control trial with permuted block randomization of nine cases per block for each parallel, open-labeled arm. SETTING AND PATIENTS: Adult patients with COVID-19 with a Pa o2 /F io2 ratio of less than 300, admitted between February 4, 2021, and August 9, 2021, to three tertiary centers in Oman, were studied. INTERVENTIONS: This study included three interventions: HFNC ( n = 47), helmet continuous positive airway pressure (CPAP; n = 52), and face-mask CPAP ( n = 52). MEASUREMENTS AND MAIN RESULTS: The endotracheal intubation rate and mortality at 28 and 90 days were measured as the primary and secondary outcomes, respectively. Of the 159 randomized patients, 151 were analyzed. The median age was 52 years, and 74% were men. The endotracheal intubation rates were 44%, 45%, and 46% ( p = 0.99), and the median intubation times were 7.0, 5.5, and 4.5 days ( p = 0.11) in the HFNC, face-mask CPAP, and helmet CPAP, respectively. In comparison to face-mask CPAP, the relative risk of intubation was 0.97 (95% CI, 0.63-1.49) for HFNC and 1.0 (95% CI 0.66-1.51) for helmet CPAP. The mortality rates were 23%, 32%, and 38% at 28 days ( p = 0.24) and 43%, 38%, and 40% ( p = 0.89) at 90 days for HFNC, face-mask CPAP, and helmet CPAP, respectively. The trial was stopped prematurely because of a decline in cases. CONCLUSIONS: This exploratory trial found no difference in intubation rate and mortality among the three intervention groups for the COVID-19 patients with hypoxemic respiratory failure; however, more evidence is needed to confirm these findings as the trial was aborted prematurely.

COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA).

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible.

Limited Sampling Strategy Using End of Infusion and Six-Hour Concentrations Overestimates Intravenous Busulfan Clearance Compared With Standard Six-Point Sampling in Hematopoietic Stem Cell Transplant Patients.

BACKGROUND: Therapeutic drug monitoring for busulfan (Bu) is important to improve outcomes of hematopoietic stem cell transplantation. However, standard therapeutic drug monitoring requires multiple samples and is inconvenient, labor-intensive, and costly. Accordingly, a limited sampling strategy (LSS) was evaluated, using 2-point sampling at end of infusion and at 6 hours, and the area-under-the-curve and Bu clearances (CLs) were compared with the results obtained from the standard sampling strategy (SSS) using 5-6 samples. METHOD: The analysis was based on retrospective clinical data from 202 patients receiving intravenous Bu before hematopoietic stem cell transplantation for malignant or nonmalignant conditions. Bu plasma concentrations were measured via liquid chromatography tandem-mass spectrometry, and pharmacokinetic parameters were calculated using the PKCNA package in R program. RESULT: A total of 502 doses were analyzed by applying SSS and LSS. Using the modified Bland-Altman plot, the mean percentage difference in CL between the SSS and LSS estimates of Bu 6-hourly regimen was -41% (Limits: -53% and -30%). In the once daily regimen, the mean difference in CL between the 2 strategies on the modified Bland-Altman plot was -22% (Limits: -66% and +22%). CONCLUSIONS: The Bu CL values estimated based on the BU concentration at end of infusion and at 6 hours postinfusion were significantly higher than the values obtained via the SSS.

Patients' knowledge and awareness of safe handling of oral anticancer agents at Sultan Qaboos University Hospital in Oman.

BACKGROUND: Safe handling of oral anticancer agents is of great concern. There is a lack of clear, national guidelines on how patients can safely handle and dispose of unwanted medications. We aimed to evaluate the safe handling, storage, and disposal of oral anticancer drugs among cancer patients and caregivers at home. METHOD: This cross-sectional survey of adult cancer patients (or their adult caregivers) used a closed-ended questionnaire from May 2019 to March 2020. RESULTS: A total of 257 patients (50 ± 15 years; range: 18-93 years) were enrolled; however, only 91% (233/257) reported self-administering oral anticancer medications. Caregivers were more likely to administer oral anticancer agents for patients ≥60 years than those <40 years old (63% vs. 8%; P = 0.001). Most patients (52%; 133/257) did not wash their hands after administering the drug; 74% (164/222) of the respondents reported that their medications were kept in a bedroom cabinet, while 18% (40/222) stored their medications in a refrigerator, and 5% (12/222) in a kitchen cabinet. A total of 55% (68/124) of patients returned their excess oral chemotherapy medications to the hospitals; however, 36% (45/124) disposed of their unused oral chemotherapy drugs in a household garbage container. CONCLUSION: While two-thirds of patients stored their oral anticancer medications properly, more than half used inappropriate handling procedures. Disposal practices were inconsistent and did not adhere to the reported international guidelines.

Molecular blood group screening in Omani blood donors.

BACKGROUND AND OBJECTIVES: Blood group genotyping has been used in different populations. This study aims at evaluating the genotypes of common blood group antigens in the Omani blood donors and to assess the concordance rate with obtained phenotypes. MATERIAL AND METHODS: Blood samples from 180 Omani donors were evaluated. Samples were typed by serological methods for the five blood group systems MNS, RH (RHD/RHCE), KEL, FY and JK. Samples were genotyped using RBC-FluoGene vERYfy eXtend kit (inno-train©). Predicted phenotypic variants for 70 red blood cell antigens among the MNS, RH (RHD/RHCE), KEL, FY, JK, DO, LU, YT, DI, VEL, CO and KN blood group systems were assessed. RESULTS: Simultaneous phenotype and genotype results were available in 130 subjects. Concordance rate was >95% in all blood group systems with exception of Fy(b+) (87%). Homozygous GATA-1 mutation leading to erythroid silencing FY*02N.01 (resulting in the Fy(b-)ES phenotype) was detected in 81/112 (72%) of genotyped samples. In addition, discrepant Fyb phenotype/genotype result was obtained in 14/112 samples; 13 of which has a heterozygous GATA-1 mutation and one sample with a wild GATA genotype. D and partial e c.733C>G variants expressing the V+VS+ phenotype were found in 22/121 (18.2%) and 14/120 (11.7%) of the samples, respectively. Di(a-b+), Js(a-b+), Yt(a+b-) and Kn(a+b-) genotype frequencies were 99.4%, 95.8%, 91.9% and 97.7%, respectively. CONCLUSION: In conclusion, we report a high frequency of FY*02N.01 allele due to homozygous c.-67T>C GATA-1 single-nucleotide variation. This is the first study reporting the detailed distribution of common and rare red cell genotypes in Omani blood donors.

Impact of Glutathione S-Transferase Polymorphisms on Busulfan Pharmacokinetics and Outcomes of Hematopoietic Stem Cell Transplantation.

BACKGROUND: Busulfan (Bu) is an alkylating drug used in many preparative regimens before hematopoietic stem cell transplantation (HSCT). It is conjugated in the liver mainly by glutathione S-transferase isoenzyme A1-1 ( GSTA1 ). Genetic polymorphisms in these isoenzymes may affect the pharmacokinetics of Bu and the clinical outcomes of HSCT. This study aimed to assess the impact of glutathione S-transferase ( GST ) genetic polymorphisms on the clearance of Bu and the clinical outcomes of patients undergoing HSCT. METHODS: This single-center retrospective study included patients who received IV Bu before HSCT at Sultan Qaboos University Hospital (SQUH), Oman from January 2003 to October 2016. Genotyping for polymorphisms was performed for GSTM1 , GSTT1 , GSTA1 , and GSTP1 . Each GST polymorphism was analyzed for its impact on Bu clearance and HSCT outcomes. RESULTS: A total of 135 patients were included. The mean Bu clearance was 3.7 ± 0.98 mL/min/kg. Patients with GSTA1 A-513G heterozygosity (AG) were found to have a higher incidence of graft loss ( P = 0.006). Homozygous double null of GSTM1 and GSTT1 was associated with a higher incidence of acute graft versus host disease ( P = 0.04). Double non-null GSTM1 and GSTT1 and non-null GSTM1 increased the risk of mortality ( P = 0.034 and 0.021, respectively). CONCLUSIONS: GST genotyping before HSCT may predict HSCT outcomes. The results of this preliminary retrospective study need to be confirmed in a larger prospective study.

Applications and challenges in therapeutic drug monitoring of cancer treatment: A review.

Most anticancer agents show wide variability in pharmacokinetics (PK) and have a narrow therapeutic index which makes fixed dosing suboptimal. To achieve the best therapeutic outcomes with these agents, many studies have postulated using PK or therapeutic drug monitoring (TDM)-guided dosing. However, multiple factors contribute to the variability in PKs making the application of TDM in practice challenging. Also, despite the known association with clinical outcomes, standard guidelines on PK-guided dosing are lacking for most agents. Understanding the factors that contribute to PK variability and their impact is essential for dose individualization. The purpose of this review is to discuss the factors that contribute to the PK variability of anticancer agents and the challenges faced in practice when individualizing doses for certain widely used agents. Searching the literature has identified several gaps and efforts are needed to ensure better targeting of cancer therapeutics.

Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial.

Importance: Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea. Objective: To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-ß0 thalassemia, or S-ß+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included. Interventions: A 1-hour 100-mg/kg loading dose of poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194). Main Outcomes and Measures: Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup. Results: Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 [45.4%] female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h [95% CI, -7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008). Adverse events that were more common in the poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%). Conclusions and Relevance: Among children and adults with SCD, poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of poloxamer 188 for vaso-occlusive episodes. Trial Registration: ClinicalTrials.gov Identifier: NCT01737814.

Cardiac T2* MR in patients with thalassemia major: a 10-year long-term follow-up.

The consequence of regular blood transfusion in patients with thalassemia major (TM) is iron overload. Herein, we report the long-term impact of chelation on liver iron concentration (LIC) and cardiac T2* MR in patients with TM. This is a retrospective cohort study over 10 years of adolescents and adults with TM aged at least 10 years who had their first cardiac T2* MR between September 2006 and February 2007. One-year chelation therapy was considered the unit of analysis. A total of 99 patients were included in this study with a median age of 18 years. The median cardiac T2* MR and LIC at baseline were 19 ms and 11.6 mg/g dw, respectively. During follow-up, 18 patients died and six underwent successful bone marrow transplantation. Factors associated with decreased survival were older age (HR 1.12, p = 0.014) and high risk cardiac T2* (HR 8.04, p = 0.004). The median cardiac T2* and LIC significantly improved over the 10-year follow-up period (p = 0.000011 and 0.00072, respectively). In conclusion, this long-term "real-life" study confirms that low cardiac T2* adversely impacts the overall survival in patients with TM. Higher baseline LIC predicts a larger reduction in LIC, and lower baseline cardiac T2* predicts a larger improvement in T2*.

Efficiency of day 4 compared to day 6 stem cell mobilization in allogeneic stem cell donors.

BACKGROUND: Granulocyte colony stimulating factor (G-CSF) given for 4-6 days is commonly used for mobilization of allogeneic stem cell donors. The primary objective of this study is to compare the yield of stem cell mobilization, assessed using a surrogate endpoint of CD34+ cell count, between Day 4 and Day 6. STUDY DESIGN AND METHODS: In this retrospective study we included all allogeneic stem cell donors mobilized with G-CSF for 6 days from January 2003 until October 2015 in the bone marrow transplantation unit at a tertiary academic center. Of 106 donor records reviewed, 84 were with available data and selected for the study. RESULTS: We included 84 donors with median age and weight of 19 years and 60 kg respectively. The median Day 4 WBC and CD34+ cell count were 37.4 × 109/L and 54 × 106/L respectively; while the median Day 6 WBC and CD34+ cell count were 44.4 × 109/L and 86 × 106/L respectively with a statistically significant difference from Day 4 (P < 0.001). In the multivariable model, there were no significant impact of donor's age (P = 0.215), weight (P = 0.108), height (P = 0.428) and mean corpuscular volume (P = 0.263) on the difference in CD34+ cell yield. However, the donor's blood group AB predicated a significantly higher difference (P = 0.036). CONCLUSION: Six days of G-CSF mobilization achieves higher CD34+ cell count than 4 days in allogeneic stem cell donors especially in donors with blood group AB, albeit both approaches give count higher than the successful collection threshold.

Impact of cell saver during cardiac surgery on blood transfusion requirements: a systematic review and meta-analysis.

OBJECTIVE: We performed a systematic review and meta-analysis of randomized clinical trials on adult patients undergoing cardiac surgery and compared the rates of red blood cell (RBC), platelet and fresh frozen plasma (FFP) transfusion between the cell saver (CS) and the standard of care groups. METHODS: MEDLINE ®, The Cochrane Central Register of Controlled Trials (CENTRAL), American Society of Hematology (ASH) and bibliographies of relevant studies were searched. We used random-effect model. RESULTS: Our search strategy returned 624 citations, of which 15 studies were selected. The use of CS did not decrease the rate of RBC transfusion (odds ratio [OR]: 0·69; 95% CI: 0·48-1·00), albeit with a substantial heterogeneity (I2  = 60%). The year of publication explained most of the heterogeneity (P for subgroup effect <0·001). Although the rate of platelet transfusion was lower in the CS group, the difference was not statistically significant (OR: 0·83; 95% CI: 0·57-1·2; I2  = 0%). The rate of FFP transfusion was numerically higher in the CS group; however, this difference did not reach statistical significance (OR: 1·26; 95% CI: 0·82-1·94; I2  = 15%). Only two studies scored five on the Jadad score. There was no indication of a publication bias using the funnel plot and Egger test (P = 0·34, 0·87, and 0·62 for RBC, platelet and FFP, respectively). CONCLUSION: The use of CS during cardiac surgery does not have an impact on the rates of RBC, platelet and FFP transfusion; however, this should be interpreted in the light of the study limitations.

Discriminatory power of the intraoperative cell salvage use in the prediction of platelet and plasma transfusion in patients undergoing cardiac surgery.

INTRODUCTION: We aim to assess the discrimination of transfused salvaged blood in predicting perioperative platelet and plasma transfusion. METHODS: Retrospective review was performed on all patients undergoing cardiac surgery with cell saver (CS) support. The area under the receiver operating characteristics curve was calculated. RESULTS: The discrimination achieved by transfused CS volumes in predicting perioperative platelet and plasma transfusion was poor (AUC 0.642 and 0.613 respectively). None of the covariates included (preoperative platelets, cardiopulmonary bypass use and time, aortic cross clamp time and use of aspirin or clopidogrel within 7 days of surgery) were statistically significant predictors. CONCLUSION: Volumes of transfused CS blood have poor discrimination in predicting platelet and plasma transfusion.

Successful management of severe hemolytic disease of the fetus due to anti-Jsb using intrauterine transfusions with serial maternal blood donations: a case report and a review of the literature.

BACKGROUND: The management of pregnant women with anti-Jsb is challenging due to the paucity of antigen-negative blood for fetal and neonatal transfusion. CASE REPORT: A 29-year-old woman with anti-Jsb was referred for assessment of recurrent fetal losses. With the presence of the sister as a historically matched donor, she was planned for active surveillance for fetal anemia during pregnancy. STUDY DESIGN AND METHODS: The fetus remained well until 21 weeks of gestation when signs of fetal anemia and early hydrops fetalis were noted. Anti-Jsb titer was at 128. The sister's red blood cells (RBCs) were cross-match incompatible. Urgent intrauterine transfusion (IUT) was performed with washed irradiated maternal RBCs, donated after cessation of heparin. The mother was given intravenous iron (IV-Fe) and continued on weekly recombinant human erythropoietin (rHu-EPO). RESULTS: Repeated IUTs were needed every 1 to 3 weeks. Throughout a 7-week period, three maternal donations were performed with total donated whole blood volume of 1250 mL, supporting four IUTs. At 29 weeks of gestation, the procedure was complicated by umbilical cord hematoma necessitating urgent cesarean section. A male newborn was delivered, transfused at birth, and subsequently treated with phototherapy and five top-up transfusions. CONCLUSION: This case represents a successful example of managing hemolytic disease of the fetus due to a rare antibody using maternal blood. It also supports previous data on safety of maternal donations during pregnancy and the use of combination of rHu-EPO and IV-Fe as a supportive measure.

Validation of a non-invasive pulse CO-oximetry based hemoglobin estimation in normal blood donors.

INTRODUCTION: Non-invasive hemoglobin estimation may increase the recruitment of blood donors. CO-oximetry hemoglobin estimation is a non-invasive method used to estimate the hemoglobin level. The primary objective of this study is to validate the pulse CO-oximetry based hemoglobin estimation in normal blood donors. METHODS: We conducted a prospective observational study on 106 in a tertiary care hospital blood bank over a period of 4 weeks. We performed a Spot Hemoglobin concentration (Sp Hb) using Masimo Pronto-7 Pulse CO-oximetry, and compared it to a venous sample Hb concentration (Reference Hemoglobin; Ref Hb) measured using Abbott CELL-DYN Sapphire hematology analyzer. Age, gender, weight, height, blood pressure and reference hemoglobin were used in the multivariable linear regression model of the difference in measurement. RESULTS: Total of 106 donors (98 males, 8 females) were enrolled with a mean age and Ref Hb of 27 years (SD 6.2; 18-49) and 14.2 g/dL (SD 1.2; 11.5-17) respectively. The mean Sp Hb was 14.4 g/dL (SD 1.2;11.3-16.7). The mean difference between the Sp Hb and Ref Hb was 0.2 g/dL (SD 1.2;-4.5 to 3) with a correlation coefficient of 0.46 (R(2)=21%). In the multivariable model, height (p=0.015) and Hb level (p<0.001) were statistically significant predictors. A strong correlation was found between the two CO-oximetry Hb measurements (coefficient 0.78, R(2)=60%). CONCLUSIONS: Our study validated the use of the CO-oximetry in blood donors. Larger prospective studies are needed to confirm our results.

Correlation of iron overload and glomerular filtration rate estimated by cystatin C in patients with ß-thalassemia major.

Historically, renal involvement has not been a commonly recognized complication in patients with ß-thalassemia major (ß-TM). Herein, we studied the impact of iron overload on glomerular filtration rate (GFR) estimated by cystatin C based GFR (Cyst C eGFR). We enrolled 149 patients with ß-TM in a cross sectional study in a single center in Oman. We investigated the correlation between measurement of serum ferritin and Cyst C eGFR. We used univariable linear regression to study the impact of serum ferritin on Cyst C eGFR and backwards stepwise regression to adjust for potential confounders. We included 78 males and 71 females with a mean age of 17.3 ± 9 years (range 2.5-38.5). Seventeen patients had diabetes mellitus. Patients were taking deferiprone (DFP) and deferoxamine (DFO) (26 patients), DFP (58 patients), deferasirox (DFX) (62 patients) and one patient was taking only DFO. There was a very weak negative linear relationship between serum ferritin and Cyst C eGFR (correlation coefficient -0.25). In the univariable analyses, serum ferritin (p = 0.004), diabetes status (p < 0.001) and chelation therapy (p < 0.001) were statistically significant. In the multivariable model, age (p = 0.033), chelation with DFX (p = 0.05) and diabetes status (p < 0.001) were statistically significant. We found a very weak inverse linear correlation between serum ferritin and Cyst C eGFR. However, when concomitant use of chelation therapy was considered, serum ferritin did not associate with glomerular function. Prospective and larger studies are needed to confirm these findings.

The Contemporary Role of Hematopoietic Stem Cell Transplantation in the Management of Chronic Myeloid Leukemia: Is It the Same in All Settings?

Hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML) patients has transitioned from the standard of care to a treatment option limited to those with unsatisfactory tyrosine kinase inhibitor (TKI) responses and advanced disease stages. In recent years, the threshold for undergoing HSCT has increased. Most CML patients now have life expectancies comparable to the general population, and therefore, the goal of therapy is shifting toward achieving treatment-free remission (TFR). While TKI discontinuation trials in CML show potential for achieving TFR, relapse risk is high, affirming allogeneic HSCT as the sole curative treatment. HSCT should be incorporated into treatment algorithms from the time of diagnosis and, in some patients, evaluated as soon as possible. In this review, we will look at some of the recent advances in HSCT, as well as its indication in the era of aiming for TFR in the presence of TKIs in CML.

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.

Consensus-Based Guidelines for Acute Myeloid Leukemia Management in Gulf Cooperation Council Countries: Addressing Unmet Regional Needs and the Changing AML Landscape.

PURPOSE: AML is a heterogeneous hematologic malignancy. Region-specific recommendations for AML management can enhance patient outcomes. This article aimed to develop recommendations for the Gulf Cooperation Council (GCC) countries. METHODS: Ten AML panel members from Kuwait, Oman, Qatar, and the United Arab Emirates (KOQU) participated in a modified two-round Delphi process. The panel first identified the unmet regional needs and finalized a list of core variables. Next, they voted on iterative statements drawn from international recommendations and provided feedback via a questionnaire. Consensus voting ≤70% was discussed, and additional clinical decision making statements were suggested. At round closure, a consensus vote took place on revised statements. RESULTS: The panel reached ≥97.8% consensus on AML management. The panel agreed to use international risk stratification categories for personalized treatment of AML. The presence of ≥10% blasts for recurrent genetic abnormalities was required for a diagnosis of AML. Key consensus was reached for different treatment stages. The panel noted that older patients pose a challenge because of poor cytogenetics and genetic anomalies and require different treatment approaches. The panel recommended venetoclax-hypomethylating agents; fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor; and targeted therapy for AML relapsed/refractory disease. Supportive care is considered on the basis of prevailing organisms and drug resistance. CONCLUSION: The GCC KOQU's consensus-based recommendations for managing AML include an evidence-based and region-specific framework.

Current Status and Management of Chronic Myeloid Leukemia in the Gulf Region: Survey Results and Expert Opinion.

Studies on chronic myeloid leukemia (CML) in the Gulf region are scarce, consisting of a survey and expert meeting that included 15 experts in 2023 which discussed CML diagnosis, testing, treatment objectives, toxicities, and discontinuation in the Gulf region. Most patients were reported to be in first-line therapy, and the most common treatments were imatinib/imatinib generic in first-line and dasatinib in second- and third-lines. Mutation analysis was not reported to be routinely performed at the time of diagnosis but rather in case of progression to accelerated/blast phase or any sign of loss of response. While all participants were aware that BCR-ABL should be monitored every three months during the first year of treatment, 10% reported monitoring BCR-ABL every six months in practice due to test cost and lab capability. The most important first-line therapy objective was "achievement of major molecular response" (MMR) in younger patients and "overall survival" in older ones. The most important treatment objectives were "MMR" and "early molecular response followed by prolongation of overall survival" in the short term and "treatment-free remission" in the long term. The current practices in CML in the Gulf region appear to be similar to global figures.