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1.
Blood ; 143(25): 2654-2665, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38493482

RESUMEN

ABSTRACT: In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that nonmyeloablative-related haploidentical bone marrow transplant (BMT) with thiotepa and posttransplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants were evaluable based on the conditioning protocol. Graft failure occurred in 8 of 70 (11.4%) and only in participants aged <18 years; all had autologous reconstitution. After a median follow-up of 2.4 years, the 2-year Kaplan-Meier-based probability of event-free survival was 82.6%. The 2-year overall survival was 94.1%, with no difference between children and adult participants. After excluding participants with graft failure (n = 8), participants with engraftment had median whole blood donor chimerism values at days +180 and +365 after transplant of 100% (n = 58), respectively, and 96.6% (57/59) were off immunosuppression 1 year after transplant. The 1-year grade 3 to 4 acute graft-versus-host disease (GVHD) rate was 10%, and the 2-year moderate-severe chronic GVHD rate was 10%. Five participants (7.1%) died from infectious complications. We demonstrate that nonmyeloablative haploidentical BMT with thiotepa and PTCy is a readily available curative therapy for most adults, even those with organ damage, compared to the more expensive myeloablative gene therapy and gene editing. Additional strategies are required for children to decrease graft failure rates. The trial was registered at www.clinicaltrials.gov as #NCT01850108.


Asunto(s)
Anemia de Células Falciformes , Trasplante de Médula Ósea , Enfermedad Injerto contra Huésped , Trasplante Haploidéntico , Humanos , Trasplante de Médula Ósea/métodos , Trasplante de Médula Ósea/efectos adversos , Masculino , Femenino , Niño , Adolescente , Adulto , Anemia de Células Falciformes/terapia , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante Haploidéntico/métodos , Preescolar , Adulto Joven , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Acondicionamiento Pretrasplante/métodos , Persona de Mediana Edad , Tiotepa/administración & dosificación , Tiotepa/uso terapéutico
2.
J Infect Dis ; 229(1): 83-94, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-37440459

RESUMEN

BACKGROUND: Human metapneumovirus (hMPV) epidemiology, clinical characteristics and risk factors for poor outcome after allogeneic stem cell transplantation (allo-HCT) remain a poorly investigated area. METHODS: This retrospective multicenter cohort study examined the epidemiology, clinical characteristics, and risk factors for poor outcomes associated with human metapneumovirus (hMPV) infections in recipients of allo-HCT. RESULTS: We included 428 allo-HCT recipients who developed 438 hMPV infection episodes between January 2012 and January 2019. Most recipients were adults (93%). hMPV infections were diagnosed at a median of 373 days after allo-HCT. The infections were categorized as upper respiratory tract disease (URTD) or lower respiratory tract disease (LRTD), with 60% and 40% of cases, respectively. Patients with hMPV LRTD experienced the infection earlier in the transplant course and had higher rates of lymphopenia, neutropenia, corticosteroid use, and ribavirin therapy. Multivariate analysis identified lymphopenia and corticosteroid use (>30 mg/d) as independent risk factors for LRTD occurrence. The overall mortality at day 30 after hMPV detection was 2% for URTD, 12% for possible LRTD, and 21% for proven LRTD. Lymphopenia was the only independent risk factor associated with day 30 mortality in LRTD cases. CONCLUSIONS: These findings highlight the significance of lymphopenia and corticosteroid use in the development and severity of hMPV infections after allo-HCT, with lymphopenia being a predictor of higher mortality in LRTD cases.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfopenia , Metapneumovirus , Infecciones por Paramyxoviridae , Infecciones del Sistema Respiratorio , Adulto , Humanos , Estudios de Cohortes , Estudios Retrospectivos , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/etiología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones por Paramyxoviridae/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Corticoesteroides/uso terapéutico
3.
Am J Hematol ; 99(6): 1023-1030, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38488686

RESUMEN

Allogeneic hematopoietic stem cell transplant (HSCT) for adults with severe sickle cell disease (SCD) is potentially curative but not commonly utilized therapy due to complications such as graft failure (GF) and organ toxicity. Herein, we are reporting our long-term outcome data of non-myeloablative (NMA) HSCT in adults with severe SCD with emphasis on factors predicting event free survival (EFS). Adults with severe SCD undergoing NMA match-related donor allogeneic HSCT from 2015 to 2021 with at least 12 months of follow-up were included. A total of 200 patients were included with a median age of 26 years (14-43) and 56% were male. The median infused CD34 dose was 13.7 (5.07-25.8), respectively. Median absolute neutrophil count engraftment was 19 (13-39) days with 51% of patients receiving GCSF to expedite recovery. A total of 17 patients experienced GF; 3 as primary and 14 as secondary within a median time of 204 days (40-905). A 76% successfully discontinued sirolimus at the last follow-up. Median follow-up for the cohort is 29.2 (2.1-71.4) months. Estimated 3-year EFS and OS were 88.2% (81.9-92.5) and 94.6% (89.2-97.3). At multivariable analysis, minor ABC incompatibility hazard ratio (HR) 4 (1.3-12.1; 0.014) and allo-antibody against non-ABO donor antigens HR 4.3 (1.3-14.1; 0.016) were significant for EFS. No clonal evolution or myeloid malignancies were seen. This largest single-center report of NMA HSCT in adults with severe SCD further delineated its feasibility, potential toxicities, and fertility outcomes. GF remains a major impediment and appears dependent on ABO matching and non-ABO antibodies.


Asunto(s)
Anemia de Células Falciformes , Trasplante de Células Madre Hematopoyéticas , Humanos , Adulto , Masculino , Femenino , Anemia de Células Falciformes/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Adolescente , Adulto Joven , Trasplante Homólogo , Resultado del Tratamiento , Acondicionamiento Pretrasplante/métodos , Enfermedad Injerto contra Huésped/etiología , Estudios de Seguimiento , Estudios Retrospectivos , Aloinjertos
4.
Br J Haematol ; 192(4): 761-768, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33534948

RESUMEN

Non-myeloablative haematopoietic progenitor cell transplantation (HPCT) from matched related donors (MRD) has been increasingly utilized in sickle cell disease (SCD). A total of 122 patients received 300 cGy of total body irradiation (TBI), alemtuzumab, unmanipulated filgrastim-mobilized peripheral blood HPC and sirolimus. The median follow-up was four years; median age at HPCT was 29 years. Median neutrophil and platelet engraftment occurred on day 22 and 19 respectively; 41 patients required no platelet transfusions. Overall and sickle-free survival at one and five years were 93% and 85% respectively. Age, sex, pre-HPCT sickle complications, ferritin and infused HPC numbers were similar between graft failure and engrafted patients. Mean donor myeloid chimaerism at one and five years post HPCT were 84% and 88%, and CD3 was 48% and 53% respectively. Two patients developed grade 1 and 2 skin graft-versus-host disease (GVHD) with no chronic GVHD. Median days of recipients taking immunosuppression were 489; 83% of engrafted patients have discontinued immunosuppression. Haemoglobin, haemolytic parameters and hepatic iron levels improved post HPCT. Pulmonary function testing, hepatic histology and neurovascular imaging remained stable, suggesting cessation of further sickle-related injury. Fourteen patients had children. In this largest group of adult SCD patients, this regimen was highly efficacious, well-tolerated despite compromised organ functions pre HPCT, and without clinically significant GVHD.


Asunto(s)
Anemia de Células Falciformes/terapia , Antígenos HLA , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Alemtuzumab/uso terapéutico , Anemia de Células Falciformes/inmunología , Antineoplásicos Inmunológicos/uso terapéutico , Niño , Femenino , Rechazo de Injerto/etiología , Rechazo de Injerto/inmunología , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/inmunología , Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Sirolimus/uso terapéutico , Donantes de Tejidos , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/métodos , Resultado del Tratamiento , Adulto Joven
5.
Biochim Biophys Acta Mol Basis Dis ; 1863(1): 239-252, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27641442

RESUMEN

B-cells of the high-grade non-Hodgkin lymphoma Burkitt's lymphoma (BL) overexpress survival oncoproteins, including the proviral integration site for Moloney murine leukaemia virus kinase (Pim)-1, and become apoptosis resistant. Activated death receptor CD95 after ligation with anti-CD95 monoclonal antibody (mAb) resulted in the regression of BL via induction of apoptosis, suggesting a decrease of survival protein expression. Here, CD95-mediated apoptotic pathways in BL B-cell lines (Raji and Daudi) following treatment with anti-CD95 mAb was investigated with the cause-and-effects on pim-1 gene expression, in comparison with leukemic cell line (K562) used as CD95-negative cells. Immunohistochemical staining for CD95 and Pim-1 was performed, and the effects of anti-CD95 mAb on apoptotic signalling using western blotting, on caspase activity and cell survival of BL B-cell and leukemic cell lines were determined. We showed that Raji cells expressed more CD95 receptors than Daudi cells. Half of each population underwent apoptosis accompanied by decreased cell viability after anti-CD95 mAb treatment. Distinct extrinsic and intrinsic CD95-mediated apoptotic pathways in Raji and Daudi cells were revealed by high caspase activity and mitochondrial outer membrane permeabilization, respectively. We observed decreased Pim-1 transcript and protein expression levels with increased heat-shock protein (Hsp)70 and decreased Hsp90 expression in anti-CD95 mAb-treated cells. Throughout the study, K562 cells did not undergo apoptosis upon anti-CD95 mAb treatment. Pim-1 knockdown following to stable transfection with plasmid vectors induced apoptosis and decreased viability of BL and K562 cells. Therefore, CD95-mediated apoptosis induces Pim-1 down-regulation in BL B-cells, but Pim-1 down-regulation cannot fully eradicate BL and leukaemia.


Asunto(s)
Apoptosis , Linfoma de Burkitt/genética , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Proteínas Proto-Oncogénicas c-pim-1/genética , Receptor fas/metabolismo , Anticuerpos Monoclonales/farmacología , Antineoplásicos Inmunológicos/farmacología , Apoptosis/efectos de los fármacos , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Linfocitos B/patología , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patología , Línea Celular Tumoral , Supervivencia Celular , Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos
6.
Cureus ; 16(2): c159, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38348202

RESUMEN

[This corrects the article DOI: 10.7759/cureus.52692.].

7.
Cureus ; 16(1): e52692, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38347977

RESUMEN

Background Multiple myeloma (MM) is a hematological malignancy characterized by the production of monoclonal immunoglobulin. It is the second-most common hematological malignancy. The survival rate varies depending on age at diagnosis, comorbidities, and treatment.This study aims to assess the prevalence of clinical and laboratory characteristics among multiple myeloma patients. Methods This is an observational study of multiple myeloma patients who were admitted to King Abdulaziz Medical City - National Guard between January 2015 and December 2020. Patient records were reviewed to derive clinical and laboratory characteristics. Descriptive data analysis and survival analysis were obtained using SPSS. Results Our study included 151 patients, 95 of whom were males and 56 were females, and the mean age of diagnosis with MM was 62.6 (SD = 13.4). Among 151 MM patients, the most common clinical signs were bone lesions and renal disease, with a percentage of 66.9% and 46.4%, respectively. Death rates throughout the time of study conduction were 19.2%, accounting for 29 patients, and the median overall survival was 5.1 years with a 95% confidence level. Testing the association between survival rates and gender showed that death rates in females were significantly higher than in males (p-value = 0.023). Patients with anemia had a significantly higher hazard ratio in both unadjusted and adjusted analyses (aHR = 2.61; 95% CI = 1.21-5.65). Conclusion There was a relationship between survival and gender, which suggests a protective factor favoring the male gender. Clinical and laboratory characteristics, including bone marrow lesions, anemia, and renal disease, were the initial presentation; thus, a detailed history focused on symptoms should be taken when any of these symptoms are reported.

8.
Transplant Proc ; 56(1): 186-190, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38242760

RESUMEN

BACKGROUND: Respiratory viral infections (RVIs) commonly cause morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. This study aimed at the prevalence of RVIs in adult HSCT recipients and their outcomes. METHODS: A retrospective observational cohort study was conducted on all adult patients who underwent HSCT in the period between January 2016 and December 2020. Data were retrospectively abstracted from electronic medical records from a total of 400 patients. All cases with polymerase chain reaction-confirmed RVIs based on real-time reverse transcription polymerase chain reaction were included in the data analysis. RESULT: A total of 79 patients had positive results. Sixty-three patients had allogeneic stem cell transplants. Women were 53% of the patients, and the mean age was 32 years (±13.5). The prevalence of documented respiratory virus infections was around 20% during the 4 years of the study. The most common virus was rhinovirus (60.76%), followed by respiratory syncytial virus (15.19%), then parainfluenza (11.39%). Among the 9 patients (11%) who required intensive care unit admission, 67% had lymphopenia (P = .03), 71% had abnormal chest computed tomography scan with pleural effusion (P = .03), 22% required renal support (P = .057), and 2 patients (22%) died (P = .057). CONCLUSIONS: The study highlights the associated morbidity and mortality with RVIs among HSCT recipients and the need for more preventive measures and treatment studies.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Infecciones del Sistema Respiratorio , Virosis , Adulto , Humanos , Femenino , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre , Virosis/epidemiología , Receptores de Trasplantes
10.
Genes (Basel) ; 14(10)2023 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-37895268

RESUMEN

BACKGROUND: Sickle cell disease (SCD) is a Mendelian disease characterized by multigenic phenotypes. Previous reports indicated a higher rate of thromboembolic events (TEEs) in SCD patients. A number of candidate polymorphisms in certain genes (e.g., FVL, PRT, and MTHFR) were previously reported as risk factors for TEEs in different clinical conditions. This study aimed to genotype these genes and other loci predicted to underlie TEEs in SCD patients. METHODOLOGY: A multi-center genome-wide association study (GWAS) involving Saudi SCD adult patients with a history of TEEs (n = 65) and control patients without TEE history (n = 285) was performed. Genotyping used the 10× Affymetrix Axiom array, which includes 683,030 markers. Fisher's exact test was used to generate p-values of TEE associations with each single-nucleotide polymorphism (SNP). The haplotype analysis software tool version 1.05, designed by the University of Göttingen, Germany, was used to identify the common inherited haplotypes. RESULTS: No association was identified between the targeted single-nucleotide polymorphism rs1801133 in MTHFR and TEEs in SCD (p = 0.79). The allele frequency of rs6025 in FVL and rs1799963 in PRT in our cohort was extremely low (<0.01); thus, both variants were excluded from the analysis as no meaningful comparison was possible. In contrast, the GWAS analysis showed novel genome-wide associations (p < 5 × 10-8) with seven signals; five of them were located on Chr 11 (rs35390334, rs331532, rs317777, rs147062602, and rs372091), one SNP on Chr 20 (rs139341092), and another on Chr 9 (rs76076035). The other 34 SNPs located on known genes were also detected at a signal threshold of p < 5 × 10-6. Seven of the identified variants are located in olfactory receptor family 51 genes (OR51B5, OR51V1, OR51A1P, and OR51E2), and five variants were related to family 52 genes (OR52A5, OR52K1, OR52K2, and OR52T1P). The previously reported association between rs5006884-A in OR51B5 and fetal hemoglobin (HbF) levels was confirmed in our study, which showed significantly lower levels of HbF (p = 0.002) and less allele frequency (p = 0.003) in the TEE cases than in the controls. The assessment of the haplotype inheritance pattern involved the top ten significant markers with no LD (rs353988334, rs317777, rs14788626882, rs49188823, rs139349992, rs76076035, rs73395847, rs1368823, rs8888834548, and rs1455957). A haplotype analysis revealed significant associations between two haplotypes (a risk, TT-AA-del-AA-ins-CT-TT-CC-CC-AA, and a reverse protective, CC-GG-ins-GG-del-TT-CC-TT-GG-GG) and TEEs in SCD (p = 0.024, OR = 6.16, CI = 1.34-28.24, and p = 0.019, OR = 0.33, CI = 0.13-0.85, respectively). CONCLUSIONS: Seven markers showed novel genome-wide associations; two of them were exonic variants (rs317777 in OLFM5P and rs147062602 in OR51B5), and less significant associations (p < 5 × 10-6) were identified for 34 other variants in known genes with TEEs in SCD. Moreover, two 10-SNP common haplotypes were determined with contradictory effects. Further replication of these findings is needed.


Asunto(s)
Anemia de Células Falciformes , Receptores Odorantes , Adulto , Humanos , Estudio de Asociación del Genoma Completo , Genotipo , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/genética , Haplotipos , Polimorfismo de Nucleótido Simple , Proteínas de Neoplasias/genética , Receptores Odorantes/genética
11.
Hematol Oncol Stem Cell Ther ; 17(1): 37-42, 2023 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-37581462

RESUMEN

BACKGROUND: Sickle cell disease (SCD) is frequently inherited worldwide. The severity of SCD ranges from mild to severe, and the disease involves multiple complications, including pulmonary hypertension, stroke, recurrent vaso-occlusive crises, end-organ damage, and an increased mortality risk. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option for patients with SCD. OBJECTIVES OF THE STUDY: The objective was to assess the quality of life of adolescent and adult patients with SCD receiving HCT pre-and post-transplant. METHODS: An analytical cross-sectional study was conducted. Patients with SCD with at least one year of follow-up after HCT were interviewed to assess their quality of life pre-and post-transplant. This study was conducted at the Transplant Center of King Abdulaziz Medical City, Riyadh. The participants were identified through non-probability consecutive sampling. The FACT-G questionnaire was used to assess the quality of life domains. RESULTS: Thirty-one patients were included. The median age of the respondents was 32 ± 6.3 years, and 16 were male (51.6%). The most frequent indication for stem cell transplantation (58%) was a vaso-occlusive crisis. The mean FACT-G scores pre- and post-transplantation were 55.2 ± 18.17 and 91 ± 14.58, respectively. The mean number of annual ER visits was significantly reduced from 27.3 pre-transplant to 6.6 post-transplant (P-value = 0.006). Of the respondents, 51.6% experienced no severe complications post-transplantation, and most (93.5%) reported improved quality of life. CONCLUSION: HCT significantly improved the quality of life of adult patients with SCD, with improvements in most FACT-G score domains. Although it was not measured by the FACT-G, the frequency of ER visits and hospital admissions were reduced significantly post-transplant, reflecting an improvement in the quality of life and a reduction in the cost of therapy for patients with SCD.


Asunto(s)
Anemia de Células Falciformes , Trasplante de Células Madre Hematopoyéticas , Hemoglobinopatías , Adulto , Adolescente , Humanos , Masculino , Femenino , Calidad de Vida , Estudios Transversales , Anemia de Células Falciformes/terapia , Anemia de Células Falciformes/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos
12.
Glob J Qual Saf Healthc ; 6(3): 81-88, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38405331

RESUMEN

Introduction: The outpatient oncology infusion unit is very busy, serving 60 to 70 patients per day. Due to a limited number of nurses, treatment chairs, only one pharmacy hood for bio-hazardous drug preparation, and other factors, patients wait a long time before starting their treatment, which affects the patient experience negatively. We conducted a quality improvement project to reduce the waiting time before starting the treatment, improve the patients' experience, and allow the unit to work more effectively through better resource utilization and accommodating more patients. Methods: A committee was formed with representatives from oncology nursing and the quality specialist, chemotherapy pharmacy supervisor, data manager, and a medical consultant (team leader). We studied baseline data of patient waiting times from January to March 2019 and the factors that contributed to delays before starting the treatment. The charge nurse identified patients who could safely have their medication released early in the morning at 7 am, enabling the pharmacy to dispense at 8 am without their actual presence being required in the infusion suite (i.e., medication early release program or MERP). Multiple plan-do-study-act (PDSA) cycles were implemented to achieve a wait time from check-in to medication administration of less than 60 minutes. Data collected included check-in time, chair time, vital signs time, administration time, and discharge time. Additionally, reasons for drug wastage were assessed for patients who did not receive the prepared medication. A patient satisfaction survey was conducted with the patients before and after being enrolled in the program. Results: At baseline, average waiting time for patients receiving similar medications in the MERP was 2 hours and 27 minutes. After the first intervention, average waiting time was reduced to 1 hour and 24 minutes, and small improvements were observed after each PDSA cycl. A major breakthrough occurred after an intensive patient education program and enforcement of strict compliance with the criteria in selecting the patients appropriate for theMERP. Average waiting time wasreduced to ≤ 60 minutes, and in November 2022, it was 30 minutes on average. Drug wastage was identified as a balancing measure. We were successful in reducing drug wastage by implementing several changes and patient education measures and achieved zero wastage. The patient satisfaction survey showed better satisfaction with the new changes. Conclusion: A positive impact was achieved in this quality improvement project, with a significant reduction in the average waiting time for patients to start receiving chemotherapy. The outcome of this project has been maintained for 4 years and is still ongoing.

13.
Leuk Res ; 130: 107316, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37245332

RESUMEN

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.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Adolescente , Adulto Joven , Niño , Estudios Retrospectivos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Doxorrubicina/uso terapéutico , Ciclofosfamida/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/efectos adversos , Vincristina/uso terapéutico , Estudios Multicéntricos como Asunto
14.
Cureus ; 14(11): e31762, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36569688

RESUMEN

Objectives We evaluated liposomal amphotericin B versus voriconazole for the treatment of invasive pulmonary aspergillosis (IPA) in patients with hematological malignancy or hematopoietic stem cell transplantation (HSCT). Methods This retrospective cohort, single-center study included patients with compatible radiological diagnosis of IPA between 2016 and 2021. Results Forty-six patients with hematological malignancy or HSCT were diagnosed with IPA. Thirty-nine of them fulfilled the criteria for comparing liposomal amphotericin B (n=15) with voriconazole (n=24). Their median age was 48.5 years. Stem cell transplant recipients were 45.65%, and nearly half of the patients (47.83%) had acute myeloid leukemia. Twenty-six (56.52%) of the patients did not require oxygen therapy. The 12-week mortality was 13.33% (two out of 15) in patients who received liposomal amphotericin B compared to 25% (six out of 24) in patients who received voriconazole. There was no mortality judged to be related to IPA. Success or global clinical response was not different between the two drugs: 80% for liposomal amphotericin B versus 83.33% for voriconazole. However, the safety profile favored liposomal amphotericin B. Conclusion In this small cohort, there was an equipoise in the mortality and clinical and radiological outcomes obtained using liposomal amphotericin B or voriconazole for the treatment of IPA in hematological malignancy or HSCT.

15.
Leuk Res Rep ; 16: 100276, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34804792

RESUMEN

Relapsed/refractory classical Hodgkin lymphoma (R/R cHL) patients refractory to first line salvage have poor outcomes. Herein we report the outcome of R/R cHL patients requiring ≥two vs. one line in the era of chemo-immunotherapy. Among 55 R/R cHL patients, 33 (60%) required one, 22 (40%) required ≥two lines. At 2 years, the estimated PFS and OS for patients requiring one vs. ≥two lines was 71.2% (50.1-84.7) vs. 51.9% (27.6-71.6), p= 0.16 and 84.6% (63-94) vs. 84% (58-95), p= 0.88, respectively. Patients requiring ≥two salvage lines prior to HCT can achieve comparable outcomes to those requiring one, possibly due to brentuximab vedotin leading to higher CMR rates.

16.
Hematol Oncol Stem Cell Ther ; 14(3): 252-256, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32201152

RESUMEN

Primary myelofibrosis (PMF) is a subtype of BCR-ABL1 negative myeloproliferative neoplasm. Its characteristic features include clonal myeloproliferation, dysregulation of kinase signaling pathway, abnormal release of cytokines leading to fibrosis in the bone marrow, osteosclerosis, and extramedullary hematopoiesis. Approximately 20% of deaths occur because of disease progression, but death may also result occur because of cardiovascular complications or as a consequence of either infection or bleeding. The only and curative option for PMF is allogeneic hematopoietic stem cell transplant (allo-HSCT); however, the Janus kinase (JAK) 1/2 inhibitor ruxolitinib is highly effective in reducing constitutional symptoms and spleen volume, and has been found to improve survival. Ruxolitinib decreases the activity of type I T-helper cells, leading to decreased release of cytokines including tumor necrosis factor-α, interleukin-1 (IL-1), IL-6, interferon-γ, and production of IL-12, which can be a risk factor for opportunistic infections. In this report, we describe three cases of tuberculosis reactivation shortly after initiation of ruxolitinib therapy followed by a literature review.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mielofibrosis Primaria/terapia , Pirazoles , Células TH1/inmunología , Tuberculosis , Anciano , Aloinjertos , Citocinas/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nitrilos , Mielofibrosis Primaria/inmunología , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Pirimidinas , Tuberculosis/inducido químicamente , Tuberculosis/inmunología
17.
Leuk Res Rep ; 15: 100240, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33936943

RESUMEN

The prognostic impact of CD20 expression and rituximab therapy in classical Hodgkin lymphoma (cHL) is unclear. Among 310 patients, CD20 was expressed in 66 (22%) cases. The 3-year PFS was 75.1% for CD20+and 70% for CD20- (p = 0.36). The 3-year PFS was 84.7% for the rituximab group and 67.8% for the no rituximab group (p = 0.23). Only constitutional symptoms and positive interim PET/CT were significantly associated with worse outcome, HR 3.2 (1.14-9.01; p = 0.028) and 4.3 (2.27-8.1; p < 0.0001), respectively. Neither CD20 expression nor rituximab use significantly impacted outcome.

18.
JCO Glob Oncol ; 7: 1220-1232, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34343012

RESUMEN

PURPOSE: Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults and is responsible for the majority of cancer-related mortality. In Saudi Arabia, leukemia is ranked the fifth most prevalent type of malignancy in adults. Our aim is to review existing epidemiologic data in Saudi Arabia and develop consensus guidelines for management of AML. METHODS: We review literature related to AML epidemiology, treatment patterns, and outcomes in Saudi Arabia, as well as literature related to the current advances in AML treatment. A panel of 10 experts from eight institutions in Saudi Arabia reviewed the literature and developed a consensus statement. RESULT: We provide an update of the available AML epidemiologic data in Saudi Arabia and describe recent developments in the diagnostic workup, risk stratification, and treatment algorithm. The consensus recommendations for the management of AML in Saudi Arabia were developed. CONCLUSION: The recommendations are in parallel with the recent international guidelines for the diagnosis and management of AML.


Asunto(s)
Leucemia Mieloide Aguda , Medicina , Médula Ósea , Consenso , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/terapia , Arabia Saudita/epidemiología
19.
J Infect Public Health ; 14(3): 353-357, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33647552

RESUMEN

BACKGROUND: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is associated with a high fatality rate (34%), which is higher in the presence of co-morbidities. The aim of the current study was to assess the clinical course and the outcome in hematological or oncological malignancy cases, diagnosed with MERS-CoV. METHODS: This is a case series of hematological /oncological cases, diagnosed with MERS-CoV, in a tertiary care setting in 2015. The cases were identified based on the World Health Organization (WHO) MERS-CoV case definition. The demographic, clinical, and outcome data were retrieved from the patients' medical charts and electronic health records. RESULTS: In total, nine hematological or oncological cases were identified, diagnosed with MERS-CoV. The baseline malignant condition was hematological malignancy in seven patients, as well as colon cancer and osteosarcoma in one patient each. Six (67%) patients were male. The median age was 65 years (range 16-80 years). Co-morbidities included chronic kidney disease (n = 3.33%), diabetes mellitus (n = 3.33%), and hypertension (n = 2.22%). The presenting symptoms were shortness of breath (n = 6.66%), fever (n = 5.55%), cough (n = 2.22%), and diarrhea (n = 2.22%). Chest x-rays indicated bilateral infiltrates in 6 patients (66%). The PCR (polymerase chain reaction) test was repeated in six patients to confirm the diagnosis. The mortality rate was 100%, and the median time to death was 26 days (range 15-77 days). CONCLUSION: MERS-CoV infection in this small cohort of hematology or oncology patients has a 100% mortality rate, regardless of the status of the underlying disease. The confirmation of the diagnosis may require repeated testing. Additional studies are required to verify the findings and to elucidate the disease pathogenesis in cancer patients.


Asunto(s)
Infecciones por Coronavirus , Enfermedades Hematológicas , Coronavirus del Síndrome Respiratorio de Oriente Medio , Neoplasias , Adolescente , Adulto , Anciano , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Femenino , Enfermedades Hematológicas/complicaciones , Humanos , Masculino , Neoplasias/complicaciones , Arabia Saudita/epidemiología
20.
Clin Lymphoma Myeloma Leuk ; 21(1): e66-e75, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32943371

RESUMEN

Histiocytic disorders are an exceptionally rare group of diseases with diverse manifestations and a paucity of approved treatments, thereby leading to various challenges in their diagnosis and management. With the discovery of novel molecular targets and the incorporation of targeted agents in the management of various adult histiocytic disorders, their management has become increasingly complex. In an attempt to improve the understanding of the clinical features and management of common adult histiocytic disorders (Langerhans cell histiocytosis, Erdheim-Chester disease, Rosai-Dorfman disease, and hemophagocytic lymphohistiocytosis), we created this document based on existing literature and expert opinion.


Asunto(s)
Enfermedad de Erdheim-Chester/tratamiento farmacológico , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Histiocitosis Sinusal/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Adulto , Quimioterapia Combinada , Enfermedad de Erdheim-Chester/diagnóstico , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis Sinusal/diagnóstico , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Resultado del Tratamiento
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