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Allogeneic hematopoietic stem cell transplantation (HSCT) is the only established curative option for Fanconi anemia (FA) associated bone marrow failure (BMF)/aplastic anemia (AA) and hematological malignancy. We performed a retrospective multicenter study on 813 FA children undergoing first HSCT between 2010 and 2018. Median duration of follow-up was 3.7 years (interquartile range, 3.4-4.0). Median age at transplant was 8.8 years (6.5-18.1). Overall survival (OS), event-free survival (EFS) and GvHD-free, relapse-free survival (GRFS) at 5 years were 83% (80-86%), 78% (75-81%) and 70% (67-74%) respectively. OS was comparable between matched family donor (MFD, n=441, 88%) and matched unrelated donor (MUD, n=162, 86%) and was superior to that of mismatched family or unrelated donor (MMFD/MMUD, n=144, 72%) and haploidentical donor (HID) (n=66, 70%, p<0.001). In multivariable analysis, a transplant indication of acute myeloid leukaemia/myelodysplastic syndrome compared to AA/BMF, use of MMFD/MMUD and HID compared to MFD, Fludarabine-Cyclophosphamide (FluCy) + other conditioning compared to FluCy independently predicted inferior OS, while alemtuzumab compared to ATG was associated with better OS. Age ï³ 10 years was associated with worse EFS and GRFS. Cumulative incidences (CIN) of primary and secondary graft failure were 2% (1-3%) and 3% (2-4%) respectively. CIN of grade II-IV acute GvHD, grade III-IV acute GvHD and chronic GvHD were 23% (20-26%), 12% (10-15%) and 8% (6-10%) respectively. The 5-year CIN of secondary malignancy was 2% (1-3%). These data suggest that HSCT should be offered to Fanconi Anemia patients with AA/BMF at a younger age in the presence of a well-matched donor.
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ABSTRACT: Studies comparing the efficacy of posttransplant cyclophosphamide (PTCy) to conventional calcineurin inhibitor (CNI)-based graft-versus-host disease (GVHD) prophylaxis regimens in patients with Hodgkin lymphoma (HL) are scarce. This study aimed to compare the outcomes of patients with HL undergoing hematopoietic stem cell transplantation (HSCT) from HLA-matched donors who received GVHD prophylaxis with either PTCy- or conventional CNI-based regimens, using data reported in the European Society for Blood and Marrow Transplantation database between January 2015 and December 2022. Among the cohort, 270 recipients received conventional CNI-based prophylaxis and 176 received PTCy prophylaxis. Notably, PTCy prophylaxis was associated with delayed hematopoietic recovery but also with a lower risk of chronic (25% vs 43%; P < .001) and extensive chronic GVHD (13% vs 28%; P = .003) compared with the CNI-based cohort. The 2-year cumulative incidence of nonrelapse mortality and relapse was 11% vs 17% (P = .12) and 17% vs 30% (P = .007) for PTCy- and CNI-based, respectively. Moreover, the 2-year overall survival (OS), progression-free survival (PFS), and GVHD-free, relapse-free survival (GRFS) were all significantly better in the PTCy group compared with the CNI-based group: 85% vs 72% (P = .005), 72% vs 53% (P < .001), and 59% vs 31% (P < .001), respectively. In multivariable analysis, PTCy was associated with a lower risk of chronic and extensive chronic GVHD, reduced relapse, and better OS, PFS, and GRFS than the CNI-based platform. Our findings suggest that PTCy as GVHD prophylaxis offers more favorable outcomes than conventional CNI-based prophylaxis in adult patients with HL undergoing HSCT from HLA-matched donors.
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Ciclofosfamida , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Humanos , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/etiología , Enfermedad de Hodgkin/terapia , Enfermedad de Hodgkin/mortalidad , Femenino , Masculino , Adulto , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Persona de Mediana Edad , Ciclofosfamida/uso terapéutico , Adolescente , Adulto Joven , Inhibidores de la Calcineurina/uso terapéutico , Inhibidores de la Calcineurina/administración & dosificación , Antígenos HLA/inmunologíaRESUMEN
ABSTRACT: Selecting the most suitable alternative donor becomes challenging in severe aplastic anemia (SAA) when a matched sibling donor (MSD) is unavailable. We compared outcomes in patients with SAA undergoing stem cell transplantation (SCT) from matched unrelated donors (MUD) (n = 1106), mismatched unrelated donors (MMUD) (n = 340), and haploidentical donors (Haplo) (n = 206) registered in the European Society for Blood and Marrow Transplantation database (2012-2021). For Haplo SCT, only those receiving posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis were included. Median age was 20 years, and the median time from diagnosis to transplantation 8.7 months. Compared with MUD, MMUD (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.52-5.6) and Haplo (HR, 5.15; 95% CI, 2.5-10.58) showed significantly higher risks of primary graft failure. MUD had lower rates of acute GVHD compared with MMUD and Haplo (grade 2-4: 13%, 22%, and 19%, respectively; P < .001; grade 3-4: 5%, 9%, and 7%, respectively; P = .028). The 3-year nonrelapse mortality rate was 14% for MUD, 19% for MMUD, and 27% for Haplo (P < .001), whereas overall survival and GVHD and relapse-free survival (GRFS) rates were 81% and 73% for MUD, 74% and 65% for MMUD, and 63% and 54% for Haplo, respectively (P < .001). In addition to donor type, multivariable analysis identified other factors associated with GRFS such as patient age, performance status, and interval between diagnosis and transplantation. For patients with SAA lacking an MSD, our findings support MUDs as the preferable alternative donor option. However, selecting between an MMUD and Haplo donor remains uncertain and requires further exploration.
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Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Donante no Emparentado , Humanos , Anemia Aplásica/terapia , Anemia Aplásica/mortalidad , Femenino , Masculino , Adulto , Adolescente , Persona de Mediana Edad , Adulto Joven , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/métodos , Niño , Preescolar , Trasplante Haploidéntico/métodos , Donantes de TejidosRESUMEN
Allogeneic hematopoietic cell transplantation (allo-HCT) is recommended for core-binding factor mutated (CBF) AML patients achieving second complete remission (CR2). However, approximately 20% of patients may relapse after transplant and donor preference remains unclear. We compared in this EBMT global multicenter registry-based analysis the allo-HCT outcomes using either haploidentical (Haplo), matched siblings donors (MSD), or 10/10 matched unrelated donors (MUD). Data from 865 de novo adult CBF AML patients in CR2 receiving allo-HCT in 227 EBMT centers from 2010 to 2022 were analyzed, in which 329 MSD, 374 MUD, and 162 Haplo-HCTs were included. For the entire cohort, 503 (58%) patients were inv(16)/CBFB-MYH11 and 362 patients (42%) were t(8;21)/RUNX1-RUNX1T1 AML. On multivariate analysis, Haplo-HCT was associated with a lower Relapse Incidence (RI) compared to either MSD (hazard ratio [HR] = 0.56, 95% CI 0.32-0.97; p < .05) or MUD (HR = 0.57, 95% CI: 0.33-0.99, p < .05). No significant difference was observed among the 3 types of donors on LFS, OS and GRFS. CBF-AML with t(8;21) was associated with both higher RI (HR = 1.79, 95% CI 1.3-2.47; p < .01) and higher NRM (HR = 1.58, 95% CI 1.1-2.27; p < .01) than CBF-AML with inv(16), which led to worse LFS, OS and GRFS. To conclude, for CBF-AML patients in CR2, Haplo-HCTs were associated with a lower RI compared to MSD and MUD allo-HCTs. There was no difference on LFS, OS or GRFS. CBF AML patients with inv(16) had a better progonosis than those with t(8;21) after allo-HCT in CR2.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Recurrencia , Hermanos , Donante no Emparentado , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/genética , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Incidencia , Anciano , Trasplante Haploidéntico/métodos , Adolescente , Sistema de Registros , Factores de Unión al Sitio Principal/genética , Adulto Joven , Inducción de Remisión , Aloinjertos , Europa (Continente)RESUMEN
Background: One of the most frequently used methods for quantifying PD-L1 (programmed cell death-ligand 1) expression in tumor tissue is IHC (immunohistochemistry). This may predict the patient's response to anti-PD1/PD-L1 therapy in cancer. Methods: ImageJ software was used to score IHC-stained sections for PD-L1 and compare the results with the conventional manual method. Results: In diffuse large B cell lymphoma, no significant difference between the scores obtained by the conventional method and ImageJ scores obtained using the option "RGB" or "Brightness/Contrast." On the other hand, a significant difference was found between the conventional and HSB scoring methods. ImageJ faced some challenges in analyzing head and neck squamous cell carcinoma tissues because of tissue heterogenicity. A significant difference was found between the conventional and ImageJ scores using HSB or RGB but not with the "Brightness/Contrast" option. Scores obtained by ImageJ analysis after taking images using 20 × objective lens gave significantly higher readings compared to 40 × magnification. A significant difference between camera-captured images' scores and scanner whole slide images' scores was observed. Conclusion: ImageJ can be used to score homogeneous tissues. In the case of highly heterogeneous tissues, it is advised to use the conventional method rather than ImageJ scoring.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias de Cabeza y Cuello , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Antígeno B7-H1/metabolismo , Proyectos de Investigación , Ligandos , Biomarcadores de Tumor/análisisRESUMEN
Background: A majority of patients included in risk assessment models (RAMs) developed to predict venous thromboembolic events (VTE) in lymphoma were non-Hodgkin lymphoma. Our study aims to evaluate the incidence and predictors of VTE, utilizing different RAMs, in patients with classic Hodgkin lymphoma (cHL) treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). Methods: Adult patients with cHL, treated and followed at our center, were included. Correlations between different variables, Khorana score, and thrombosis in lymphoma (ThroLy) RAMs with VTE were examined using Fisher's exact test and logistic regression analysis. Results: A total of 321 patients were included, with a median age of 29 (range: 18-83) years. Of them, 169 (52.6%) had advanced-stage disease. Combined modality treatment was given to 169 (52.6%) patients. A total of 52 (16.2%) patients had relapsed or refractory disease. VTE were reported in 15 (4.7%) patients and were mostly during the administration of first-line (n = 8, 53.3%), or salvage chemotherapy (n = 6, 40.0%). There was no correlation between a Khorana score > 2 (p = 0.689) or ThroLy score > 3 (p = 0.335) and VTE. Older age (p = 0.014) and relapsed or refractory disease (p = 0.003) significantly correlated with VTE. Conclusions: VTE are uncommon in cHL. The commonly used RAMs failed to predict VTE. However, older age and relapsed or refractory disease significantly increased this risk.
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Background: In early stage diffuse large B-cell lymphoma (ESDLBL), tumor bulkiness is an important determinant of treatment and prognosis. Tumor bulk is usually measured on transverse computed tomography (CT) plane and variably defined from 5 to 10 cm. Objectives: Our study aims to investigate the prognostic significance of bulky disease measured on CT coronal and transverse planes and to evaluate the outcome of patients with bulky disease. Methods: Patients with ESDLBL and treated with rituximab, cyclophosphamide, doxorubicin, and prednisolone (RCHOP) with or without radiotherapy were included. Receiver Operating Characteristic (ROC) analysis was used to identify the optimal tumor dimension that correlated with progression, relapse, or death. Correlation between different variables and progression-free survival (PFS) and overall survival (OS) were analyzed using log-rank (Mantel-Cox) test and Cox proportional hazard models. Results: A total of 127 patients with a median age of 47 (range: 18-90) years were included. Eighty-two (64.6%) patients treated with combined modality treatment (CMT) [RCHOP + radiotherapy]. After a median follow-up of 40 (range: 2-114) months, 3-year PFS and OS were 83.9% (95% CI: 76.759%-89.981%), and 80.6% (95% CI: 72.499%-87.531%), respectively. Tumor dimension of >7.5 cm measured on either CT plane was the optimal cutoff point to define bulky disease. Three-year PFS and OS were inferior in the group of patients with no bulky disease on transvers plane (n = 84) but had bulky disease on coronal plane (n = 9,10.7%); (94.2% vs. 75%, p = 0.017 and 90.5% vs. 56.3%, p = 0.002), as well as in patients with no bulky disease on coronal plane (n = 89), but had bulky disease on transverse plane (n = 14, 15.7%); (94.1% vs. 62.3%, p < 0.001, and 90.4% vs. 63.5%, p = 0.002). Compared to RCHOP alone, 3-year PFS and OS were better in patients with bulky disease treated with CMT (78% vs. 52.5%, p = 0.018 and 81.8% vs. 38.7%, p = 0.003) but not in patients with non-bulky disease (96.2% vs. 93%, p = 0.691 and 87.6% vs. 91.5%, p = 0.477). Conclusion: In ESDLBL, measurement of tumor mass on transverse and coronal CT planes may help in better identification of patients with bulky disease. The use of CMT was associated with better survival outcomes in patients with bulky disease.
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BACKGROUND AND OBJECTIVES: Early T-cell precursor (ETP) acute lymphoblastic leukemia/lymphoma (ALL/LBL) is a newly recognized entity of T-lymphoblastic leukemia/lymphoma. The optimal therapeutic approaches to adult patients are poorly studied. PATIENTS AND METHODS: We compared the outcomes of adult's patents with ETP-ALL/LBL who received frontline chemotherapy regimens with other T-ALL/LBL immunophenotypic subtypes. Patients with ETP-ALL/LBL were identified based on CD1a (-), CD8 (-), CD5 (-) (dim), and positivity for 1 or more stem cell or myeloid antigens. RESULTS: Sixty-nine patients were included between the years 2010 and 2021 (19 ETP-T-ALL/LBL; 50 non ETP- T-cell ALL/LBL). The median age was 26 year (IQR: 21, 33). Fifty-six patients presented as ALL, while 16 with lymphoblastic lymphoma. Forty-seven patients achieved complete remission, and 43 were alive at last encounter. The complete remission rate in patients with ETP-ALL/LBL was lower than that of non-ETP-ALL/LBL patients (32% vs. 68%; P = .2), and the MRD at end of induction was significantly higher (26% vs. 6.2%, P < .001), and more likely to receive allo-SCT consolidation in CR1 (95% vs. 40%, P < .001). After a median follow-up of survivors of 48 months (range: 32-74 months), the median overall survival for patients with ETP-ALL/LBL was not reached versus 11.5 months for the non-ETP-ALL/LBL patients (P = .014)). Twenty-six patients receive allo-SCT in CR1. There was no significant difference in overall survival (79% vs. 70%; P = .49) between both transplant-cohorts in both groups. CONCLUSION: ETP-ALL/LBL represents a high-risk disease subtype of adult ALL. Novel treatment strategies are needed to improve treatment outcomes in this patient's population.
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Linfoma , Leucemia-Linfoma Linfoblástico de Células Precursoras , Células Precursoras de Linfocitos T , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Adulto , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Pronóstico , Jordania , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológicoRESUMEN
Hematopoietic cell transplantation (HCT) is a potentially curative therapy for patients with high-risk malignant and nonmalignant conditions. Nevertheless, various post-allogeneic HCT (allo-HCT) complications with diverse chronology, etiology, and pathophysiological background can develop, including general and organ-specific complications, such as graft dysfunction, infectious, and non-infectious etiologies, as well as non-infectious pulmonary complications (NIPCs). Post-transplant complications can also be related to conditioning intensity and drug-specific side effects. However, treatment options for these complications are suboptimal at present. Poor graft function (PGF) is a potentially life-threatening post-allo-HCT complication and is reported in 5-30% of patients. Nevertheless, consensus guidelines to define and treat PGF are not available. Most therapies are symptomatic with variable success rates. NIPCs are diverse and difficult to diagnose. The pathophysiology of NIPCs remains ill-defined, and effective treatment approaches have not been standardized, with mortality exceeding 50% for some conditions, such as idiopathic pneumonia syndrome (IPS). Modification of the conditioning regimen intensity and introduction of novel agents have been used to decrease post-allo-HCT complications, including infections, non-infectious complications, graft-versus-host disease (GvHD), as well as cardiopulmonary, neurological, hepatorenal, and other complications. Transplant-associated thrombotic microangiopathy (TA-TMA) is a lethal post-allo-HCT complication that may be associated with functional and genetic abnormalities in complement activation and related to the use of calcineurin inhibitors, such as cyclosporine and tacrolimus. The introduction of complement inhibitors has transformed TA-TMA from a lethal complication to a treatable syndrome.
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OBJECTIVES: Patterns and predictors of relapse in primary gastric diffuse large B cell lymphoma (DLBCL) were variably reported. Our study aims to evaluate the patterns and predictors of relapse in early-stage gastric DLBCL treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone (RCHOP). METHODS: From 2005 to 2019, the medical records of 72 patients with stage I or stage II gastric DLBCL treated with six cycles of RCHOP without radiotherapy were reviewed. Different variables were correlated with progression free survival (PFS), overall survival (OS), and local relapse free survival (LRFS). RESULTS: 64 (88.1%) patients achieved a complete response (CR), while 8 (11.9%) had refractory disease. After CR, 9 (14%) patients relapsed; 7 (78%) relapses were loco-regional. Abnormal LDH (p = 0.028), H. pylori negative (p = 0.032) and, stage adjusted international prognostic index (sa-IPI) > 1 (p = 0.013) correlated with loco-regional failure. The 5-year PFS, OS, and LRFS were 74.8%, 75.3%, and 87.5%, respectively, after a median follow-up of 58 (range: 6-185) months. The median time to progression or relapse was 9 months (range: 5-54 months). In multivariate analysis, a sa-IPI >1 (HR: 3.56, CI: 1.35-8.8, p = 0.01) was associated with PFS while low albumin (HR: 8.85, CI: 1.09-71.4, p = 0.041) was associated with worse OS. None of the variables were associated with LRFS. CONCLUSION: Treatment of primary gastric DLBCL with RCHOP results in a high CR rate. The majority of treatment failures were loco-regional. Sa-IPI and H. pylori status may be used to identify patients who may benefit from combined modality treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Humanos , Supervivencia sin Enfermedad , Prednisona , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Rituximab/uso terapéutico , Ciclofosfamida , Vincristina , Doxorrubicina , Estudios RetrospectivosRESUMEN
Background: Data on whether the graft CD3-positive (CD3+) T-cell dose in T-cell-replete human leukocyte antigen (HLA)-mismatched allogeneic hematopoietic peripheral blood stem cells transplantation (PBSCT) influences post-transplant outcomes are controversial. Methods: Using King Hussein Cancer Center (KHCC) Blood and Marrow Transplantation (BMT) Registry database, 52 adult subjects, receiving the first T-cell-replete HLA-mismatched allogeneic hematopoietic PBSCT for acute leukemias or myelodysplastic syndrome, were identified, from January 2017 to December 2020. The cutoff value of graft CD3+ T-cell dose was identified using the receiver operating characteristic (ROC) formula and Youden's analysis. Subjects were divided into two cohorts: cohort 1 with low CD3+ T-cell dose (n = 34) and cohort 2 with high CD3+ T-cell dose (n = 18). Correlative analyses were performed between CD3+ T-cell dose and the risk of graft-versus-host disease (GvHD), relapse, relapse-free survival (RFS), and overall survival (OS). P-values were two-sided and considered significant when P < 0.05. Results: Subject covariates were displayed. Subject's characteristics were comparable, except for higher nucleated cells and more female donors in the high CD3+ T-cell cohort. The 100-day cumulative incidence of acute GvHD (aGvHD) was 45±7% and 3-year cumulative incidence of chronic GvHD (cGvHD) was 28±6.7%. There was no statistically significant difference between the two cohorts in aGvHD (50% vs. 39%, P = 0.4) or cGvHD (29% vs. 22%, P = 0.7). The 2-year cumulative incidence of relapse (CIR) was 67.5±16.3% for low compared with 14.3±6.8% for high CD3+ T-cell cohort (P = 0.018). Fifteen subjects relapsed and 24 have died, 13 due to disease relapse. There was an improvement in 2-year RFS (94% vs. 83%; P = 0.0022) and 2-year OS (91% vs. 89%; P = 0.025) in low CD3+ T-cell cohort compared with high CD3+ T-cell cohort. Graft CD3+ T-cell dose is the only significant risk factor for relapse (P = 002), and OS (P = 0.030) in univariate analysis which was maintained in multivariate for relapse (P = 0.003), but not for OS (P = 0.050). Conclusions: Our data suggest that high graft CD3+ T-cell dose is associated with lower risk of relapse, and might improve long-term survival, but has no influence on the risk of developing aGvHD or cGvHD.
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Purpose: Primary mediastinal large B-cell Lymphoma (PMLBCL) is a rare aggressive lymphoma with unique clinical, pathological, and molecular features. The optimal frontline therapyâ¯is subject of ongoing debate. Our study aims to evaluate the outcomes of PMLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) at King Hussein Cancer Center. Patients and Methods: Adult patients >18 years of age with PMLBCL treated with RCHOP from January 2011 to July 2020 were identified. All demographics, disease and treatment related variables were retrospectively collected. Correlations of clinical and laboratory variables with progression-free survival (PFS) and overall survival (OS) were determined by univariate and multivariate analyses using backward stepwise Cox regression models. The PFS and OS were plotted using KaplanâMeier curves. Results: 49 patients were included with a median age of 29 years. 14 (28.6%) had stage III or IV, 31 (63.3%) had mediastinal bulky disease. International prognostic index (IPI) was 0-1 in 35 (71.4%). Radiotherapy was given to 32 (65.3%) patients. End of treatment (EOT) response was complete (CR) in 32 (65.3%), partial response (PR) in 8 (16.3%) and progressive disease (PD) in 9 (18.4%). Patients who achieved CR at EOT, compared favorably with those who did not in regard to 4-year OS (92.5% vs 26.9%, p=<0.001). Overall objective response to salvage chemotherapies was 26.7%. At a median follow-up of 46 months, 4-year PFS and OS were 60% and 71% respectively. In multivariate analysis, IPI > one correlated with the EOT response (p=0.009), PFS (p=0.004) and OS (p= 0.019). Conclusion: In PMLBCL, RCHOP chemotherapy backbone in the frontline therapy is suboptimal but can be used in patients with low IPI. Adapting more intensive chemoimmunotherapy regimens may be considered for patients with high IPI. Salvage chemotherapy has limited activity in patients with relapsed or refractory disease.
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Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Busulfano/efectos adversos , Tiotepa , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Incidencia , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicaciones , Vidarabina/efectos adversos , Acondicionamiento Pretrasplante/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Estudios RetrospectivosRESUMEN
BACKGROUND: Cancer patients are at higher risk of serious complications of COVID-19. Few studies evaluated the impact of COVID-19 on cancer patients in low- and middle-income countries. Our study aims to evaluate the outcomes of COVID-19 infection in cancer patients treated at our institution. Methods: Medical records of patients with a positive COVID-19 polymerase chain reaction (PCR) between April 2020 and October 2020 were reviewed. Fisher's exact test and logistic regression analysis were employed to correlate various variables with mortality. Survival estimates were generated using the Kaplan-Meier method. RESULTS: A total of 317 patients were included, with a median age was 55 years (range: 19-88). 82 (25.9%) had hematological neoplasms while the remainder had solid cancers. At the time of infection, 220 (69.4%) had active cancer, and 99 (31.2%) had received systemic anticancer treatment (SACT) within four weeks. Hospitalization was required for 101 (31.8%), 17 (5.3%) were admitted to the ICU and 50 (15.8%) died. Among patients with active cancer, SACT was delayed or discontinued in 140 (63.6%) patients. In the entire patient cohort, low albumin (p=<0.001) and leucocytosis (p=<0.001) correlated with mortality within six months of COVID-19 infection. The six-month mortality rate in patients with active cancer was significantly higher in patients with hypertension (p=0.024), no recent SACT (0.017), hematological cancer (p=0.029), low albumin (p=<0.001), leucocytosis (p=0.002) and lymphocyte count of less than 500/µL (p=0.004). Recent chemotherapy was associated with better 6-month survival rates (78.8% vs 89.9%, p=0.012) in patients with active cancer, patients with solid cancers (95.9% vs 82.2%, p=0.006) and was non-inferior in patient with hematological neoplasms (72% vs 65.4%, p=0.519). Conclusion: COVID-19 infection in our cancer patients was associated with significant morbidity and mortality and adversely affected their treatment. The decision to delay or discontinue SACT should be individualized, considering other risk factors for mortality.
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The aim of the study was to assess the predictive value of interim FDG-PET/CT (iPET) in patients with Hodgkin's lymphoma (HL) treated with Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy. A total of 245 consecutive patients with de novo HL between 12/2013 and 12/2017 were evaluated retrospectively. All patients were treated with upfront ABVD, performed PET/CT scans at baseline, after 2 cycles (interim PET, iPET2) or 4 cycles (iPET4) and at the end of therapy, and followed up for at least 6 months after therapy. The response status on iPET was defined according to the standard five-point Deauville scores (DS) as follows: complete metabolic response (CMR, DS 1-3) and non-complete metabolic response (nCMR) (DS 4 and 5). End-of-treatment (EoT) response was assessed by FDG-PET/CT and if needed biopsy confirmation of PET-positive findings. The association between iPET and EoT response was investigated using logistic regression analysis. Survival analysis was performed using the Cox regression hazard model and Kaplan-Meier methods. Sixty-nine patients underwent iPET-2 and 176 iPET-4. No association was found between the timing of iPET and iPET response status (P-value = 0.71). Two hundred and one patients (82%) had iPET-CMR and 44 (18%) iPET -nCMR. iPET was strongly associated with EoT response status: 194/201 (96 .5%) of iPET-CMR had a complete response at the EoT while only 21/44 (47.7%) of patients with iPET-nCMR presented a complete response at EoT (P-value < 0.0001). The median follow-up was 32 months (range 6-81). Patients with iPET-CMR presented a better outcome with 91% 3 y event-free-survival (EFS) and 95% 3 y overall survival (OS) than those with iPET-nCMR (41 and 86%, respectively, P-value < 0.0001). In multivariable analyses, iPET retained an independent prognostic factor of EFS and OS (P-value < 0.0001 and P-value = 0.002, respectively). iPET is highly predictive of outcome of HL patients treated with ABVD and allows to tailor therapy to the individual patient.
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Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Fluorodesoxiglucosa F18/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Vinblastina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios Retrospectivos , Dacarbazina/uso terapéutico , Bleomicina/efectos adversos , Doxorrubicina , Tomografía de Emisión de Positrones/métodosRESUMEN
INTRODUCTION: Checkpoint inhibitors demonstrated significant efficacy in relapsed/refractory Hodgkin's Lymphoma (R/R cHL) resulting in high responses and prolonged progression free survival in patients, who relapse after or are ineligible for autologous stem cell transplantation (auto-SCT). We aimed to assess the efficacy and toxicity of Pembrolizumab before auto-SCT and in transplant naïve patients and calculate survival outcomes. PATIENTS AND METHODS: Fifty-five patients with R/R cHL were included. Patients demographics, including age, sex, risk stratification, therapy received and details pertaining transplantation, were collected. RESULTS: Median age was 28 years (range, 16-62 years). The median follow-up was 15.3 months and the median number of previous treatments was 3 (1-10). The best objective response was 74.5% (CR 32.7%, SD 5.5%) with reasonable safety profile. Twenty-nine of the responding patients received subsequent auto-SCT and 9 allogeneic stem cell transplantation (allo-SCT), 6 are currently alive with ongoing response. At the time of analysis, 6 patients remained on Pembrolizumab and the rest discontinued. The main reason for discontinuation was disease progression (n-49). Twelve-months overall survival and progression free survival (PFS) was 92% (95% CI: 76%-95%) and 51% (95% CI, 39%-67%) respectively. Twelve-month PFS for patients, who achieved CR or PR or PD was 88% (95% CI: 07%-75%); PR 60% (95% CI: 21%-29%) and 5% (95% CI: 5%-0%). Though the number of patients who received auto-SCT after Pembrolizumab was small (n-15), 12 months overall survival and PFS 100% and PFS 92%. 11 patients (20%) deceased during the follow-up and none was regarded to be treatment-related. CONCLUSION: Checkpoint inhibitors are effective in heavily pretreated cHL patients with reasonable survival outcomes. The results supporting the concept of auto and/or allo-SCT after checkpoint inhibitors use.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Adulto , Anticuerpos Monoclonales Humanizados , Supervivencia sin Enfermedad , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Recurrencia Local de Neoplasia/terapia , Estudios Retrospectivos , Trasplante Autólogo/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: The treatment of adult Burkitt lymphoma with pediatric-based chemotherapy protocols usually results in high cure rates, although with significant toxicity. We report our experience with the Cancer and Leukemia Group B1002 (CALGB 1002) protocol. METHODS: The files of adult patients diagnosed with Burkitt lymphoma and treated with the CALGB 1002 protocol at King Hussein Cancer Center between 2008 and 2017 were reviewed. Baseline demographics, clinical laboratory features, treatment details, and responses were collected. The correlations between clinical and laboratory variables with event-free survival (EFS) and overall survival (OS) were determined by univariate and multivariate analyses using backward stepwise Cox regression models. EFS and OS were plotted using KaplanâMeier curves. RESULTS: This study included 19 patients with a median age of 33 years (range, 19â65). Eleven (58%) and two (10.5%) patients had advanced-stage and central nervous system disease, respectively. Among 106 administered cycles, the median interval between cycles was 23 days (range, 19â84 days). Sixteen patients (84%) achieved a complete response. After a median follow-up of 40.8 months, the 3-year EFS and OS rates were 78.95%. Patients with a low-risk International Prognostic Index (IPI) had better survival than those with intermediate-or high-risk IPI. Grade IIIâIV hematological toxicities occurred in 88% of patients, while 73% had grade IIIâIV mucositis. CONCLUSION: In adult Burkitt lymphoma, the CALGB 1002 protocol provides high cure rates and can be administered promptly, but is associated with significant toxicity. Risk-adapted approaches and other, less toxic, chemotherapeutic regimens should be considered.
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INTRODUCTION: extramedullary acute myeloid leukemia (eAML) is characterized by extramedullary tumor formation infiltrated by myeloid blasts, with or without maturation and effaced architecture. The clinical, genetic and molecular aspects and overall outcomes are well defined worldwide, but not well characterized in our region. PURPOSE AND METHODS: This is a retrospective single center cohort study on 32 patients, who were identified over 10 years to study the clinical, pathologic and genetic-molecular aspects, and survival outcomes. RESULTS: eAML is rare (1%), occurs at a younger age with male predominance. Central nervous system (CNS) with facial bone invasion is most commonly identified (34.4%). 45.5% were positive for conventional myeloid markers (MPO), CD33, CD117, and 36% positive for CD34 and CD68. 54% with normal karyotype had deleterious mutations on further testing. NGS revealed pathogenic mutations in 76%(N-9/17) and none tested positive for P53, IDH1 or IDH2. At a median follow up time of 43mo (range, 8.6-80mo); 37.5%(N-12) were in complete remission, 62.5%(N-20) relapsed. 28% of relapses were after allotransplant. 31%(N-10) alive and continued in complete remission(CR), and 69%(N-22) of patients have died.Median overall survival (OS) is 18.4 and relapse free survival (RFS) 18.7 months. OS and RFS were significantly better in patients, who attained CR after induction (IC 11.9 mo vs zero; P = 0.0001; IC 12mo vs zero; P = 0.0001) compared to patients with relapsed disease; and in patients who received allo-transplant consolidation with median OS and RFS 42 vs 8.5mo (P = 0.002) and 42months vs 10 mo (P = 0.006). Thus allotransplant may be considered for all eligible patients in first CR. CONCLUSION: achievement of complete remission after induction therapy is associated with improved outcomes in eAML. Allotransplant in first complete remission may be the most effective modality for achieving long-term remissions.
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BACKGROUND: Patients with aggressive lymphomas are at higher risk for venous thromboembolism (VTE). ThroLy is a risk assessment model (RAM) derived to predict the occurrence of VTE in various types of lymphomas. In this study, we assess the clinical application of ThroLy RAM in a unified group of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Hospital databases were searched for patients with DLBCL and radiologically-confirmed VTE. Items in the ThroLy RAM, including prior VTE, reduced mobility, obesity, extranodal disease, mediastinal involvement, neutropenia and hemoglobin < 10.0â g/dL, were retrospectively reviewed. RESULTS: A total of 524 patients, median age 49 (range: 18-90) years were included. Patients had high disease burden; 57.3% with stage III/IV and 34.0% with bulky disease. All were treated on unified guidelines; 63 (12.0%) had primary refractory disease. Venous thromboembolic events were reported in 71 (13.5%) patients. Among 121 patients with high (> 3) ThroLy score, 22.3% developed VTE compared to 8.4% and 12.4% in those with low and intermediate risk scores, respectively (P = .014). Simplifying the ThroLy model into two risk groups; high-risk (score ≥ 3) and low risk (score < 3) can still segregate patients; VTE developed in 44 (17.2%) high-risk patients (n = 256) compared to 27 (10.1%) in the low-risk group (n = 268), P = .038. Neutropenia, a component of the ThroLy, was encountered in only 14 (2.7%) patients. CONCLUSIONS: ThroLy RAM can identify patients with DLBCL at high risk for VTE. Model can be modified by dividing patients into two, rather than three risk groups, and further simplified by omitting neutropenia.