RESUMO
PURPOSE: Adolescent and young adult cancer survivors (AYACS) are patients diagnosed with cancer between 15 and 39 years of age. AYACS are often derailed from planned educational and occupational endeavors due to disruption from cancer treatment and its consequences. The study objective was to examine how a personal cancer diagnosis impacted AYACS' experiences related to these endeavors. METHODS: Semi-structured interviews were conducted as part of a larger study assessing psychosocial challenges among a younger AYACS subset aged 15-25 years old at the time of cancer diagnosis. Interviews were coded based on responses and were used to develop themes related to educational and occupational endeavors. RESULTS: Data were collected from 35 participants. Five themes emerged: (1) Pauses in educational attainment had a detrimental effect on educational goals for some participants, but further solidified and sculpted educational plans for others; (2) Although participants experienced challenges accomplishing educational goals, supportive school environments helped surmount these challenges; (3) Participants reflected on rethinking career aspirations, though some desired to pursue the same occupation planned before cancer diagnosis; (4) Participants experienced challenges, including physical and cognitive limitations, upon returning to work; and (5) Participants valued autonomy and normalcy through work and appreciated supportive and flexible work environments. CONCLUSIONS: AYACS prioritize professional achievement, yet encounter challenges in achieving professional goals. Our findings create a foundation for developing and testing prospective interventions to promote continuance of school and work during cancer treatment when feasible, and proactive reintegration strategies for those who paused professional goals due to cancer treatment.
Assuntos
Sobreviventes de Câncer , Pesquisa Qualitativa , Humanos , Sobreviventes de Câncer/psicologia , Adolescente , Masculino , Feminino , Adulto Jovem , Adulto , Neoplasias/psicologia , Entrevistas como Assunto , Escolaridade , Escolha da ProfissãoRESUMO
Primary graft failure (PGF) and multi-lineage cytopenia (MLC) increase the risk of nonrelapse mortality in allogeneic hematopoietic cell transplants (HCT). We evaluated the impact of post-transplant cyclophosphamide (PTCy) and splenomegaly on PGF and MLC for hematological malignancies. This study included patients with PTCy (N=84) and conventional graft-vs.-host disease prophylaxis (N=199). The occurrence of splenomegaly varied widely, ranging from 17.1â¯% (acute myeloid leukemia) to 66.7â¯% (myeloproliferative neoplasms). Ten patients (N=8 in the PTCy and N=2 in the non- PTCy) developed PGF, and 44 patients developed MLC (both N=22). PTCy and severe splenomegaly (≥20â¯cm) were risk factors for PGF (odds ratio (OR): 10.40, p<0.01 and 6.74, p=0.01 respectively). Moreover, severe splenomegaly was a risk factor for PGF in PTCy patients (OR: 10.20, p=0.01). PTCy (hazard ratio (HR) 2.09, p=0.02), moderate (≥15, <20â¯cm, HR 4.36, p<0.01), and severe splenomegaly (HR 3.04, p=0.01) were independent risk factors for MLC. However, in subgroup analysis in PTCy patients, only mild splenomegaly (≥12, <15â¯cm, HR 4.62, p=0.01) was a risk factor for MLC. We recommend all patients be screened for splenomegaly before HCT, and PTCy is cautioned in those with splenomegaly.
Assuntos
Ciclofosfamida , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Esplenomegalia , Humanos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Esplenomegalia/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Doença Enxerto-Hospedeiro/etiologia , Adolescente , Adulto Jovem , Idoso , Rejeição de Enxerto/etiologia , Transplante Homólogo/efeitos adversos , Fatores de Risco , Estudos Retrospectivos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Neoplasias Hematológicas/terapia , Criança , CitopeniaRESUMO
BACKGROUND: Bacterial prophylaxis with a fluoroquinolone (FQ) during autologous stem cell transplant (ASCT) is common, although not standardized among transplant centers. The addition of doxycycline (doxy) to FQ prophylaxis was previously linked to reduced neutropenic fever and bacteremia in multiple myeloma (MM) patients undergoing ASCT although several confounders were present. We compared the incidence of neutropenic fever and bacteremia between MM patients variably receiving prophylaxis with FQ alone and FQ-doxy during ASCT. METHODS: Systematic retrospective chart review of MM patients who underwent ASCT between January 2016 and December 2021. The primary objective was to determine the effect of bacterial prophylaxis on neutropenic fever and bacteremia within 30 days of ASCT. Multivariable logistic regression for neutropenic fever and univariate logistic regression for bacteremia accounted for differences in subject characteristics between groups. RESULTS: Among 341 subjects, 121 received FQ and 220 received FQ-doxy for prophylaxis. Neutropenic fever developed in 67 (55.4%) and 87 (39.5%) subjects in the FQ and FQ-doxy groups, respectively (p = .005). Bacteremia was infrequent, with 5 (4.1%) and 5 (2.3%) cases developing in the FQ and FQ-doxy groups, respectively (p = .337). Among Gram-negative bacteremia events, 7/7 Escherichia coli strains were FQ-resistant, and 5/7 were ceftriaxone-resistant. CONCLUSION: The FQ-doxy prophylaxis group had fewer cases of neutropenic fever than the FQ group, however, there was no significant difference in bacteremia. High rates of antibiotic resistance were observed. An updated randomized controlled trial investigating appropriate prophylaxis for ASCT in the context of current oncology standards and changing antimicrobial resistance rates is warranted.
Assuntos
Bacteriemia , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Doxiciclina/uso terapêutico , Antibacterianos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Transplante Autólogo/efeitos adversos , Antibioticoprofilaxia , Bacteriemia/epidemiologia , Bacteriemia/prevenção & controle , Bacteriemia/microbiologiaRESUMO
Acute myeloid leukemia patients with induction failure or relapsed refractory disease have minimal chance of achieving remission with subsequent treatments. Several trials have shown the feasibility of clofarabine-based conditioning in allogeneic stem cell transplants (allo-HSCT) for non-remission AML patients. Pre-transplant conditioning with clofarabine followed by reduced-intensity allo-HSCT has also demonstrated a potential benefit in those patients with human leukocyte antigen (HLA)-identical donors, but it is not commonly used in haploidentical and mismatched transplants. In this case report, we describe our experience of seven cases of non-remission AML who received clofarabine preconditioning followed by an allo-HSCT with PTCy. The 2-year overall survival and disease-free survival was 83.3% (95% confidence interval (CI): 27.3-97.9%) and 85.7% (95% CI: 33.4-97.9%). Median days of neutrophil and platelet recovery were 16 (range of 13-23) and 28 (range of 17-75), respectively. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) at day 100 and chronic GVHD at 1-year showed 28.6% (95% CI: 8-74.2%) and 28.6% (95% CI: 3-63.9%), respectively. The two-year relapse rate was 14.3% (95% CI: 2.14-66.6%). One-year GVHD-free relapse-free survival (GFRS) at 1-year was 71.4% (95% CI: 25.8-92%). Our patients showed successful outcomes with clofarabine preconditioning to reduce the leukemic burden at the pre-transplant period followed by PTCy to reduce GVHD resulting in lower relapsed rate and better GFRS in these patients.
Assuntos
Doença Enxerto-Hospedeiro , Leucemia Mieloide Aguda , Humanos , Clofarabina , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia Mieloide Aguda/terapia , AloenxertosRESUMO
Acute myeloid leukemia (AML) is a devastating blood cancer with poor prognosis. Novel effective treatment is an urgent unmet need. Immunotherapy targeting T cell exhaustion by blocking inhibitory pathways, such as PD-1, is promising in cancer treatment. However, results from clinical studies applying PD-1 blockade to AML patients are largely disappointing. AML is highly heterogeneous. Identification of additional immune regulatory pathways and defining predictive biomarkers for treatment response are crucial to optimize the strategy. CD26 is a marker of T cell activation and involved in multiple immune processes. Here, we performed comprehensive phenotypic and functional analyses on the blood samples collected from AML patients and discovered that CD26lowPD-1+ CD8 T cells were associated with AML progression. Specifically, the percentage of this cell fraction was significantly higher in patients with newly diagnosed AML compared to that in patients achieved completed remission or healthy controls. Our subsequent studies on CD26lowPD-1+ CD8 T cells from AML patients at initial diagnosis demonstrated that this cell population highly expressed inhibitory receptors and displayed impaired cytokine production, indicating an exhaustion status. Importantly, CD26lowPD-1+ CD8 T cells carried features of terminal exhaustion, manifested by higher frequency of TEMRA differentiation, increased expression of transcription factors that are observed in terminally exhausted T cells, and high level of intracellular expression of granzyme B and perforin. Our findings suggest a prognostic and predictive value of CD26 in AML, providing pivotal information to optimize the immunotherapy for this devastating cancer.
Assuntos
Leucemia Mieloide Aguda , Receptor de Morte Celular Programada 1 , Humanos , Receptor de Morte Celular Programada 1/metabolismo , Dipeptidil Peptidase 4/metabolismo , Linfócitos T CD8-Positivos , Resultado do TratamentoRESUMO
INTRODUCTION: Haematopoietic stem cell transplant (HSCT) in adults is an intensive medical procedure for a variety of haematological malignancies. Although there is a large body of evidence demonstrating the negative effects of HSCT on physical function and psychosocial parameters, there is limited evidence on the impact of HSCT on body composition and bone health. Further, aerobic and resistance-training exercise interventions aimed at improving physical function and patient-reported outcomes largely take place during the peritransplant and post-transplant period. Prehabilitative exercise, or exercise prior to medical treatment, has been successfully deployed in presurgical candidates and other tumour sites, yet there is a paucity of evidence on the effect of prehabilitation in HSCT patients. The aim of this study is to investigate the feasibility, acceptability and safety of a resistance training exercise programme in patients with haematological malignancies prior to HSCT. METHODS AND ANALYSIS: IMpact of PRehabilitation in Oncology Via Exercise-Bone Marrow Transplant is a single-site, pilot randomised controlled trial of an exercise intervention compared with usual care. The primary aim is to assess the feasibility, acceptability and safety of the resistance-training exercise intervention prior to HSCT. Secondary aims include evaluating the differences in physical function, body composition, bone mineral density and patient-reported outcomes between the exercise group and usual care control group. Outcome measurements will be assessed: prior to HSCT, on/around day of HSCT admission, +30 days post-HSCT and +100 days post-HSCT. The exercise intervention is a home-based resistance training exercise programme that incorporates resistance band and body weight exercises. The primary outcomes will be reported as percentages and/or mean values. The secondary outcomes will be analysed using appropriate statistical methods to portray within-group and between-group differences. ETHICS AND DISSEMINATION: The study has Penn State College of Medicine approval. Results will be disseminated through scientific publication and presentation at exercise-related and oncology-related scientific meetings. TRIAL REGISTRATION NUMBER: NCT03886909.
Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Adulto , Exercício Pré-Operatório , Projetos Piloto , Exercício Físico , Terapia por Exercício/métodos , Neoplasias Hematológicas/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Full donor T-cell chimerism (FDTCC) after allogeneic stem cell transplant (allo-SCT) has been associated with improved outcomes in hematologic malignancy. We studied if donor human leukocyte antigen (HLA) mismatch improves achievement of FDTCC because mismatched HLA promotes donor T-cell proliferation where recipient T-cells had been impaired by previous treatment. Patients (N = 138) received allo-SCT with reduced-intensity conditioning (RIC) from 39 HLA mismatched donors (16 unrelated; 23 haploidentical) with post-transplant cyclophosphamide (PTCy) or 99 matched donors (21 siblings; 78 unrelated) with PTCy (N = 18) or non-PTCy (N = 81). Achievement of FDTCC by day 100 was higher with HLA mismatched donors than matched donors (82.1% vs. 27.3%, p < 00,001), which was further improved with 200 cGy total body irradiation (87.9%) or lymphoid (versus myeloid) malignancy (93.8%). Since all mismatched transplants used PTCy, FDTCC was higher with PTCy than non-PTCy (68.4% vs. 25.7%, p < 0.00001), but not in the matched transplant with PTCy (38.9%), negating PTCy as the primary driver. Lymphocyte recovery was delayed with PTCy than without (median on day + 30: 100 vs. 630/µL, p < 0.0001). The benefit of FDTCC was not translated into survival outcomes, especially in myeloid malignancies, possibly due to the insufficient graft-versus-tumor effects from the delayed lymphocyte recovery. Further studies are necessary to improve lymphocyte count recovery in PTCy transplants.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Quimerismo , Doença Enxerto-Hospedeiro/etiologia , Linfócitos T , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco/efeitos adversos , Antígenos HLA , Condicionamento Pré-Transplante/efeitos adversos , Doadores não Relacionados , Estudos RetrospectivosRESUMO
Despite the increased usage of post-transplant cyclophosphamide (PTCy) in allogeneic hematopoietic stem cell transplantation (allo-HSCT), our knowledge of immune reconstitution post-allo-HSCT in the setting of PTCy is limited. Adequate immune reconstitution is the key to a successful transplant. In this study, we aim to investigate the effect of PTCy on the reconstitution of each immune component; more focus was placed on the immunophenotype and functions of T cells. Using blood samples from patients who underwent allo-HSCT under regimens containing PTCy (n = 23) versus those who received no PTCy (n = 14), we examined the impact of PTCy on the post-transplant immune response. We demonstrated a distinct T cell immune signature between PTCy versus non-PTCy group. PTCy significantly delayed T cell reconstitution and affected the T cell subsets by increasing regulatory T cells (Treg) while reducing naïve T cells. In addition, we observed remarkable enhancement of multiple inhibitory receptors (TIGIT, PD-1, TIM-3, CD38, CD39) on both CD4+ and CD8+ T cells on day 30 post-transplantation in patients who received PTCy. Importantly, upregulation of PD-1 on CD8 T cells was persistent through day 180 and these T cells were less functional, manifested by reduced cytokine production upon anti-CD3/CD28 stimulation. Furthermore, we found a significant correlation of T cell immune phenotypes to clinical outcome (disease relapse and GVHD) in patients who received PTCy. Our novel findings provide critical information to understand the mechanism of how PTCy impacts immune reconstitution in allo-HSCT and may subsequently lead to optimization of our clinical practice using this treatment.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Linfócitos T CD8-Positivos , Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Receptor de Morte Celular Programada 1/uso terapêuticoRESUMO
We report an unusual case of a woman in her 60s diagnosed with monomorphic epitheliotropic intestinal T-cell lymphoma who required a pancreatoduodenectomy (Whipple procedure) for duodenal obstruction. The patient was initially treated with several cycles of chemotherapy, with persistent disease of the duodenum at D3. She was symptomatic with obstructive symptoms and positron emission tomography (PET)-CT showed disease localised to the duodenum without evidence of active disease elsewhere. The patient underwent pancreatoduodenectomy for both palliation of obstructive symptoms and potential oncological benefit. The patient had mild symptoms of delayed gastric emptying requiring promotility agents postoperatively, but otherwise recovered well after surgery. Unfortunately, surgical pathology revealed diffuse disease through the resected portion of the duodenum and jejunum, with positive proximal and distal margins. We suspect she has diffuse small bowel disease which was occult by CT and PET-CT. Based on this case, we recommend consideration of bypass rather than resection when possible for surgical palliation due to likelihood for extensive bowel involvement.
Assuntos
Obstrução Duodenal , Linfoma de Células T , Obstrução Duodenal/cirurgia , Feminino , Humanos , Linfoma de Células T/patologia , Pancreaticoduodenectomia/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada por Raios XRESUMO
Richter syndrome (RS) represents a transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) to aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), which is associated with a dismal prognosis. Patients with DLBCL-RS have poor outcomes with DLBCL-directed therapy; thus, consolidation with hematopoietic cell transplantation (HCT) has been used, with durable remissions observed. Studies reporting HCT outcomes in patients with DLBCL-RS have been small, have not evaluated the prognostic impact of cytogenetic risk factors, and were conducted prior to the era of novel targeted therapy of CLL/SLL. We performed a Center for International Blood and Transplant Research registry study evaluating outcomes after autologous HCT (auto-HCT; n = 53) and allogeneic HCT (allo-HCT; n = 118) in patients with DLBCL-RS treated in the modern era. More auto-HCT recipients were in complete response (CR) at HCT relative to allo-HCT recipients (66% vs 34%), whereas a higher proportion of allo-HCT recipients had 17p deletion (33% vs 7%) and had previously received novel agents (39% vs 10%). In the auto-HCT cohort, the 3-year relapse incidence, progression-free survival (PFS), and overall survival (OS) were 37%, 48%, and 57%, respectively. Among allo-HCT recipients, the 3-year relapse incidence, PFS, and OS were 30%, 43%, and 52%, respectively. In the allo-HCT cohort, deeper response at HCT was associated with outcomes (3-year PFS/OS, 66%/77% CR vs 43%/57% partial response vs 5%/15% resistant; P < .0001 for both), whereas cytogenetic abnormalities and prior novel therapy did not impact outcomes. In our study, HCT resulted in durable remissions in therapy-sensitive patients with DLBCL-RS treated in the era of targeted CLL/SLL therapy, including patients with high-risk features.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Crônica de Células B , Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/terapia , Prognóstico , Transplante AutólogoRESUMO
Acute myeloid leukemia (AML) relapse after allogeneic stem cell transplant (alloSCT) remains a major therapeutic challenge. While patients with longer remission after initial alloSCT are recommended to receive cell therapy (CT) such as 2ndalloSCT or donor lymphocyte infusion (DLI), survival for patients who relapse within 6 months of alloSCT has been dismal. We evaluated the outcomes of AML relapse after alloSCT to assess the impact of different treatments on long-term survival. One hundred and seventy-two patients with AML underwent alloSCT at the Penn State Cancer Institute from January 2014 to August 2019. Sixty-nine patients relapsed (median age, 60 years; range, 10-75). Of these, 4 patients underwent 2ndalloSCT, and 26 received DLI. One-year overall survival (OS) in all cases was 20.3% (95% CI: 11.8-30.4%). Patients with ECOG performance status (PS) 0-2 at relapse showed a better 1-year OS than those with PS 3-4. Median OS for patients who received chemotherapy only or chemotherapy with CT was 74 or 173.5 days, respectively (p < 0.001). Relapsed patients receiving conventional re-induction chemotherapy were categorized as the high-intensity chemotherapy (H) group, while those receiving treatments such as hypomethylating agents or targeted agents were categorized as the low-intensity chemotherapy (L) group. The H group showed a better 1-year OS compared with the L group. Patients who received H + CT showed a better 1-year OS of 52.9% than the other 3 groups (p < 0.001). Even for patients with post-alloSCT remission duration of less than 6 months, the statistical significance was preserved. Factors including age, donor source at 1stalloSCT, time to relapse, blast counts, PS at relapse, and treatment type after post-alloSCT relapse were used for a multivariate analysis, and matched or mismatched related donor and H + CT after alloSCT were identified as independent factors associated with OS. These findings support the use of H + CT as the treatment option of choice for AML patients who relapse after alloSCT when feasible.
Assuntos
Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/terapia , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Criança , Feminino , Humanos , Transfusão de Linfócitos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Patients with hematological malignancies (HM) often require ICU admission, and acute respiratory or renal failure are then independent risk factors for mortality. Data are scarce on acute liver dysfunction (ALD), despite HM patients cumulating risk factors. The objective of this retrospective cohort study was to assess the prevalence of ALD in critically ill HM patients and its impact on outcome. Data of all patients with HM admitted to the medical ICU between 2008 and 2018 were extracted from electronic medical records. ALD was defined by ALT > 165 U/L, AST > 230 U/L, or total bilirubin > 4 mg/dL. Univariate and multivariate logistic regressions were used to analyze hospital mortality. Charts of survivors with ALD were reviewed to assess impact of ALD on subsequent anti-cancer treatment. We included 971 patients (60% male), age 64 (54-72) years, of whom 196 (20%) developed ALD. ALD patients were younger, more frequently had liver cirrhosis or acute leukemia, and had increased severity of illness and vital organ support needs. ALD was associated with hospital mortality in univariate (OR 4.14, 95% CI 2.95-5.80, p < 0.001) and multivariate analysis (OR 1.86, 95% CI 1.07-3.24, p = 0.03). Hospital mortality was 46% in ALD patients; among 106 survivors, a third of patients requiring therapy received it as previously planned, and half of the patients were alive at 1 year. In summary, in a large population of critically ill patients with hematological malignancies, 20% developed ALD, which was an independent risk factor for hospital mortality and occasionally altered further anti-cancer treatment.
Assuntos
Estado Terminal/mortalidade , Neoplasias Hematológicas/mortalidade , Falência Hepática Aguda/mortalidade , Idoso , Estudos de Coortes , Estado Terminal/terapia , Feminino , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Mortalidade Hospitalar/tendências , Humanos , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Acute myeloid leukemia (AML) is a devastating blood cancer with poor prognosis. Immunotherapy targeting inhibitory pathways to unleash the antileukemia T-cell response is a promising strategy for the treatment of leukemia, but we must first understand the underlying molecular mechanisms. Eomesodermin (Eomes) and T-bet are both T-box transcription factors that regulate CD8+ T-cell responses in a context-specific manner. Here, we examined the role of these transcription factors in CD8+ T-cell immunity in AML patients. We report that the frequency of Eomes+T-betlow CD8+ T cells increased in newly diagnosed AML. This cell subset produced fewer cytokines and displayed reduced killing capacity, whereas depletion of Eomes by siRNA reversed these functional defects. Furthermore, Eomes bound the promoter of T-cell immunoglobulin and ITIM domain (TIGIT) and positively regulated the expression of this inhibitory receptor on patient-derived T cells. A high frequency of Eomes+T-betlow CD8+ T cells was associated with poor response to induction chemotherapy and shorter overall survival in AML patients. These findings have significant clinical implications as they not only identify a predictive and prognostic biomarker for AML, but they also provide an important target for effective leukemia therapeutics. SIGNIFICANCE: These findings reveal that a high frequency of Eomes+T-betlow CD8+ T cells predicts poor clinical outcome in AML and that targeting Eomes may provide a therapeutic benefit against AML.
Assuntos
Linfócitos T CD8-Positivos/metabolismo , Leucemia Mieloide Aguda/patologia , Proteínas com Domínio T/metabolismo , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/imunologia , Prognóstico , Regiões Promotoras Genéticas , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Análise de Sobrevida , Resultado do TratamentoRESUMO
Approximately 30-40% of patients with acute myeloid leukemia (AML) experience induction failures. In these patients who do not achieve remission with two cycles of standard induction therapies, the probability of achieving remission with subsequent inductions is very limited. Hematopoietic stem cell transplantation (HSCT) is the only curative option for these patients, but high relapse rate and transplant-related mortality often preclude them to proceed to transplant. Thus, AML not in remission at time of HSCT remains a huge unmet need in current HSCT practice, particularly if the patient does not have an HLA-matched donor identified by the time of two induction failures. We used clofarabine cytoreduction immediately followed by fludarabine (Flu) and busulfan (Bu) × 3 with total-body irradiation (TBI) conditioning (Flu/Bu3/TBI) for haploidentical peripheral blood stem cell transplant with post-transplant cyclophosphamide for two cases of refractory AML with a very high tumor burden at transplant and achieved complete remission by day + 30 in both cases.
Assuntos
Nucleotídeos de Adenina/administração & dosagem , Arabinonucleosídeos/administração & dosagem , Bussulfano/administração & dosagem , Terapia Combinada/métodos , Ciclofosfamida/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressores/administração & dosagem , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/métodos , Vidarabina/análogos & derivados , Adulto , Clofarabina , Humanos , Masculino , Indução de Remissão , Resultado do Tratamento , Carga Tumoral , Vidarabina/administração & dosagemRESUMO
IMPORTANCE: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a rare peripheral T-cell lymphoma, is increasing in incidence. However, many practitioners who treat patients with breast cancer are not aware of this disease. OBJECTIVES: To assess how BIA-ALCL develops, its risk factors, diagnosis, and subsequent treatment and to disseminate information about this entity to the medical field. EVIDENCE REVIEW: A literature review was performed in an academic medical setting. All review articles, case reports, original research articles, and any other articles relevant to BIA-ALCL were included. Data on BIA-ALCL, such as pathophysiology, patient demographics, presentation, diagnosis, treatment, and outcomes, were extracted. Particular focus was paid to age, time to onset, implant type, initial symptoms, treatment, and survival. The search was conducted in January 2017 for studies published in any year. FINDINGS: After duplicates were excluded, 304 relevant articles were assessed, and 115 were included from the first documented case in August 1997 through January 2017. Thirty review articles, 44 case reports or series, 15 original research articles, and 26 "other" articles (eg, techniques, special topics, letters) were reviewed. A total of 93 cases have been reported in the literature, and with the addition of 2 unreported cases from the Penn State Health Milton S. Hershey Medical Center, 95 patients were included in this systematic review. Almost all documented BIA-ALCL cases have been associated with a textured device. The underlying mechanism is thought to be due to chronic inflammation from indolent infections, leading to malignant transformation of T cells that are anaplastic lymphoma kinase (ALK) negative and CD30 positive. The mean time to presentation is approximately 10 years after implant placement, with 55 of 83 (66%) patients initially seen with an isolated late-onset seroma and 7 of 83 (8%) with an isolated new breast mass. Ultrasonography with fluid aspiration can be used for diagnosis. Treatment must include removal of the implant and surrounding capsule. More advanced disease may require chemotherapy, radiotherapy, and lymph node dissection. CONCLUSIONS AND RELEVANCE: Breast implant-associated anaplastic large cell lymphoma is a rare cancer in patients with breast implants but is increasing in incidence. It is important for all physicians involved in the care of patients with breast implants to be aware of this entity and be able to recognize initial symptoms.
Assuntos
Implantes de Mama/efeitos adversos , Neoplasias da Mama/etiologia , Linfoma Anaplásico de Células Grandes/etiologia , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Linfoma Anaplásico de Células Grandes/diagnósticoRESUMO
IMPORTANCE: Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies. OBJECTIVE: To determine whether greater EOR is associated with improved 1- and 2-year overall survival and 6-month and 1-year progression-free survival in patients with GBM. DATA SOURCES: Pubmed, CINAHL, and Web of Science (January 1, 1966, to December 1, 2015) were systematically reviewed with librarian guidance. Additional articles were included after consultation with experts and evaluation of bibliographies. Articles were collected from January 15 to December 1, 2015. STUDY SELECTION: Studies of adult patients with newly diagnosed supratentorial GBM comparing various EOR and presenting objective overall or progression-free survival data were included. Pediatric studies were excluded. DATA EXTRACTION AND SYNTHESIS: Data were extracted from the text of articles or the Kaplan-Meier curves independently by investigators who were blinded to each other's results. Data were analyzed to assess mortality after gross total resection (GTR), subtotal resection (STR), and biopsy. The body of evidence was evaluated according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria and PRISMA guidelines. MAIN OUTCOME AND MEASURES: Relative risk (RR) for mortality at 1 and 2 years and progression at 6 months and 1 year. RESULTS: The search produced 37 studies suitable for inclusion (41â¯117 unique patients). The meta-analysis revealed decreased mortality for GTR compared with STR at 1 year (RR, 0.62; 95% CI, 0.56-0.69; P < .001; number needed to treat [NNT], 9) and 2 years (RR, 0.84; 95% CI, 0.79-0.89; P < .001; NNT, 17). The 1-year risk for mortality for STR compared with biopsy was reduced significantly (RR, 0.85; 95% CI, 0.80-0.91; P < .001). The risk for mortality was similarly decreased for any resection compared with biopsy at 1 year (RR, 0.77; 95% CI, 0.71-0.84; P < .001; NNT, 21) and 2 years (RR, 0.94; 95% CI, 0.89-1.00; P = .04; NNT, 593). The likelihood of disease progression was decreased with GTR compared with STR at 6 months (RR, 0.72; 95% CI, 0.48-1.09; P = .12; NNT, 14) and 1 year (RR, 0.66; 95% CI, 0.43-0.99; P < .001; NNT, 26). The quality of the body of evidence by the GRADE criteria was moderate to low. CONCLUSION AND RELEVANCE: This analysis represents the largest systematic review and only quantitative systematic review to date performed on this subject. Compared with STR, GTR substantially improves overall and progression-free survival, but the quality of the supporting evidence is moderate to low.
Assuntos
Neoplasias Encefálicas/cirurgia , Glioblastoma/cirurgia , Encéfalo/patologia , Encéfalo/cirurgia , Neoplasias Encefálicas/mortalidade , Intervalo Livre de Doença , Glioblastoma/mortalidade , Humanos , Risco , Resultado do TratamentoRESUMO
BACKGROUND: Patients with common variable immunodeficiency (CVID) have an increased risk of developing lymphoproliferative diseases, including non-Hodgkins lymphoma (Blood 116:1228-1234, 2010; Blood 119:1650-7, 2012). The incidence and prognosis of Hodgkin lymphoma in this population is not clear, with only a few case reports in the literature. Conventional cytotoxic chemotherapy, although highly efficacious in treating Hodgkin lymphoma in immune competent patients, is problematic in patients with CVID due to the increased risk of infectious complications (Ther Umsch 69:687-91, 2012; Pediatr Hematol Oncol 24:337-42, 2012). Rituximab and brentuximab vedotin are both targeted agents used to treat lymphomas that express CD20 and CD30, respectively. Compared to cytotoxic chemotherapy typically used in Hodgkin lymphoma, these agents are better tolerated with minimal side effects. This makes them an attractive option for treating lymphoma in patients who have significant co-morbidities, including those with immune deficiencies. Additionally, rituximab has been used safely to treat autoimmune cytopenias in patients with CVID5. However, the role of these targeted therapies in CVID-associated Hodgkin lymphoma has not been reported. CASE PRESENTATION: Here we report the case of a 25 year old female diagnosed with CVID-associated classic Hodgkin lymphoma, who achieved a complete remission following treatment with rituximab followed by brentuximab vedotin. CONCLUSIONS: We demonstrate that rituximab and brentuximab are likely safe and effective in CVID-associated Hodgkin lymphoma, providing a feasible and potentially optimal treatment option for this patient population.