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1.
Cells ; 13(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38727291

RESUMO

Refractory acute myeloid leukaemia is very difficult to treat and represents an unmet clinical need. In recent years, new drugs and combinations of drugs have been tested in this category, with encouraging results. However, all treated patients relapsed and died from the disease. The only curative option is allogeneic transplantation through a graft from a healthy donor immune system. Using myeloablative conditioning regimens, the median overall survival regimens is 19%. Several so-called sequential induction chemotherapies followed by allogeneic transplantation conditioned by reduced intensity regimens have been developed, improving the overall survival to 25-57%. In the allogeneic transplantation field, continuous improvements in practices, particularly regarding graft versus host disease prevention, infection prevention, and treatment, have allowed us to observe improvements in survival rates. This is true mainly for patients in complete remission before transplantation and less so for refractory patients. However, full myeloablative regimens are toxic and carry a high risk of treatment-related mortality. In this review, we describe the results obtained with the different modalities used in more recent retrospective and prospective studies. Based on these findings, we speculate how allogeneic stem cell transplantation could be modified to maximise its therapeutic effect on refractory acute myeloid leukaemia.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Transplante Homólogo , Humanos , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Doença Enxerto-Hospedeiro/prevenção & controle
2.
Cytopathology ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38686982

RESUMO

OBJECTIVE: The introduction of cytological screening with the Papanicolau smear significantly reduced cervical cancer mortality. However, Pap smear examination can be challenging, being based on the observer ability to decode different cytological and architectural features. This study aims to evaluate the malignancy rate of AGC (atypical glandular cells) category, investigating the relationships between cytological and histological diagnosis. METHODS: Eighty-nine patients, diagnosed as AGC at cytological evaluation and followed up with biopsy or surgical procedure at Policlinico Gemelli Hospital, Rome, Italy, were included in the study. The cytopathological architectural (feathering, rosette formation, overlapping, loss of polarity, papillary formation, three-dimensional formation) and nuclear (N/C ratio, nuclear enlargement and hyperchromasia, mitoses, nuclei irregularity, evident nucleoli) features of AGC were evaluated. Statistical analyses were performed to assess cyto-histological correlation and determine the relevance of architectural and nuclear features in the diagnosis of malignancy. RESULTS: Of the 89 AGC patients, 48 cases (53.93%) were diagnosed as AGC-NOS and 41 (46.07%) were diagnosed as AGC-FN, according to the Bethesda classification system. The follow-up biopsies or surgical resections revealed malignancy in 46 patients (51.69%). The rates of malignancy for AGC-NOS and AGC-FN were 35.41% and 70.73% respectively. Furthermore, analysing cytopathological features, we found that both architectural and nuclear criteria were statistically significant (p < 0.05). Only overlapping, nuclear irregularity and increased N/C ratio were not found to be statistically significant for detecting malignancy. CONCLUSIONS: Cytological diagnosis of glandular lesions remains a valid tool, when appropriate clinical correlation and expert evaluation are available.

3.
Ann Hematol ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38609726

RESUMO

Blinatumomab is a bispecific T-cell engager approved for relapsed/refractory and minimal residual disease positive B-cell Acute Lymphoblastic Leukemia. We conducted a retrospective study evaluating the outcome of Blinatumomab. The impact of clinical and treatment-related variables on cumulative incidence of relapse/progression (CIRP), event-free (EFS) and overall survival (OS) was analyzed. From January 2016 to December 2022 50 Ph'- (37) and Ph+ (13) B-ALL patients received Blinatumomab. The median age was 37. Indications to blinatumomab were relapsed/refractory B-ALL in 29 and MRD-positive in 21 patients. Blinatumomab was the 2nd and 3rd line in 40 and in 10 patients, respectively. Twenty patients were treated pre-transplantation, ten were treated for relapse after transplant, twenty were not eligible for transplant. Out of 29 patients treated for relapsed/refractory disease, 16 (55%) achieved complete response and 12 achieved MRD-negativity. Out of 21 patients treated for MRD, 16 (76%) achieved MRD-negativity. At a median follow-up of 46 months the median EFS and OS were 11.5 and 16.2 months. The CIRP was 50%. In univariate analysis age, disease-status (overt vs. minimal disease) at blinatumomab, bridging to transplant after blinatumomab and MRD-response resulted significant for EFS and OS. In multivariate analysis only disease-status and MRD-response retained significance both for EFS and OS. Disease-status and MRD-response resulted significant for EFS and OS also after censoring at HSCT. This retrospective study on B-ALL patients treated with blinatumomab confirms a superior outcome for MRD-responsive over MRD non-responsive patients. Survival depends also on the disease-status prior treatment.

4.
J Exp Clin Cancer Res ; 43(1): 75, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38459559

RESUMO

BACKGROUND: Breast Cancer (BC) can be classified, due to its heterogeneity, into multiple subtypes that differ for prognosis and clinical management. Notably, triple negative breast cancer (TNBC) - the most aggressive BC form - is refractory to endocrine and most of the target therapies. In this view, taxane-based therapy still represents the elective strategy for the treatment of this tumor. However, due variability in patients' response, management of TNBC still represents an unmet medical need. Telomeric Binding Factor 2 (TRF2), a key regulator of telomere integrity that is over-expressed in several tumors, including TNBC, has been recently found to plays a role in regulating autophagy, a degradative process that is involved in drug detoxification. Based on these considerations, we pointed, here, at investigating if TRF2, regulating autophagy, can affect tumor sensitivity to therapy. METHODS: Human TNBC cell lines, over-expressing or not TRF2, were subjected to treatment with different taxanes and drug efficacy was tested in terms of autophagic response and cell proliferation. Autophagy was evaluated first biochemically, by measuring the levels of LC3, and then by immunofluorescence analysis of LC3-puncta positive cells. Concerning the proliferation, cells were subjected to colony formation assays associated with western blot and FACS analyses. The obtained results were then confirmed also in mouse models. Finally, the clinical relevance of our findings was established by retrospective analysis on a cohort of TNBC patients subjected to taxane-based neoadjuvant chemotherapy. RESULTS: This study demonstrated that TRF2, inhibiting autophagy, is able to increase the sensitivity of TNBC cells to taxanes. The data, first obtained in in vitro models, were then recapitulated in preclinical mouse models and in a cohort of TNBC patients, definitively demonstrating that TRF2 over-expression enhances the efficacy of taxane-based neoadjuvant therapy in reducing tumor growth and its recurrence upon surgical intervention. CONCLUSIONS: Based on our finding it is possible to conclude that TRF2, already known for its role in promoting tumor formation and progression, might represents an Achilles' heel for cancer. In this view, TRF2 might be exploited as a putative biomarker to predict the response of TNBC patients to taxane-based neoadjuvant chemotherapy.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Estudos Retrospectivos , Taxoides/farmacologia , Taxoides/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Linhagem Celular Tumoral
5.
Pathol Res Pract ; 255: 155182, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38335782

RESUMO

BACKGROUND: Primary and metastatic leiomyosarcomas (LMS) involving the orbital region are well known to occur however, the conjunctiva represents an extremely rare site of occurrence. METHODS: A 97-year-old male was referred to the Ocular Oncology Unit due to a rapidly growing painful mass (16×12×20 mm) in the nasal conjunctiva of his left eye. Wide excision followed by radiotherapy was performed. RESULTS: Based on the microscopic features (hypercellular neoplasm composed of spindle cells with cigar shaped and blunt ended nuclei with brightly eosinophilic fibrillary cytoplasm) and immunohistochemical findings (positive staining for Vimentin, Desmin, Caldesmon, and SMA and negative staining for AE1/AE3, EMA, CD117, S100, MelanA, SOX10, HMB45, TLE1, CD99, EMA and AE1 / AE3) the final diagnosis of grade 2 leyomiosarcoma was rendered. Moreover, 'in deep' DNA sequencing (>500 genes analysis) revealed a neoplasm with high TMB: 64 muts/Mb and numerous VUS and several pathogenic/oncogenic molecular alterations, including CNV loss or gain in > 10 genes. At the last follow-up visit, residual disease was observed in the superior fornix, at the nasal limbus and the cornea. At the time of writing, after a follow-up of 2 month the patients is still alive without evidence of metastatic disease. CONCLUSION: An uncommon molecular finding observed in our case was the presence of TSC1 gene mutation usually associated with soft tissue and gynecological PEComas. Our finding may harbor important therapeutic implications since the inactivation of the tumor suppressor genes TSC1 and TSC2 lead to upregulation of mTOR signaling, providing the rationale for target therapy with mTOR inhibitors. Additional studies on larger series are needed to validate our findings.


Assuntos
Leiomiossarcoma , Neoplasias Cutâneas , Masculino , Humanos , Idoso de 80 Anos ou mais , Leiomiossarcoma/genética , Leiomiossarcoma/patologia , Imuno-Histoquímica , Proteínas de Ligação a Calmodulina , Núcleo Celular/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise
6.
Int J Mol Sci ; 25(2)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38256131

RESUMO

Among the four endometrial cancer (EC) TCGA molecular groups, the MSI/hypermutated group represents an important percentage of tumors (30%), including different histotypes, and generally confers an intermediate prognosis for affected women, also providing new immunotherapeutic strategies. Immunohistochemistry for MMR proteins (MLH1, MSH2, MSH6 and PMS2) has become the optimal diagnostic MSI surrogate worldwide. This review aims to provide state-of-the-art knowledge on MMR deficiency/MSI in EC and to clarify the pathological assessment, interpretation pitfalls and reporting of MMR status.


Assuntos
Neoplasias Encefálicas , Neoplasias Colorretais , Neoplasias do Endométrio , Síndromes Neoplásicas Hereditárias , Feminino , Humanos , Imuno-Histoquímica , Prognóstico , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Biomarcadores , Coloração e Rotulagem
7.
Tumori ; 110(1): 44-48, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37726962

RESUMO

BACKGROUND: Immunotherapy has revolutionized the approach to metastatic triple-negative breast cancers. Atezolizumab was approved for patients with metastatic triple-negative breast cancers whose tumors express PD-L1, determined by SP 142 assay. To assess the availability and practice of SP142 test we administered a survey to all the 15 pathology departments of the Lazio Region during a six-month period. METHODS: The survey comprised 12 questions regarding the availability of SP142 in the pathology departments, the percentage of positive tests, the difficulties of pathologists in cases close to cut-off value and the tested samples. RESULTS: The SP142 assay was available in only eight centers. In case of positive result, most centers (5/8, 62.5%) reported values of PD-L1 expression ranging from > 1 to ⩽ 5%, with values close to the cut-off point (⩾ 1% or < 1%) being the greatest challenge.Most of the centers (6/8, 75%) tested material from both their own and other hospitals. In most centers, the evaluations were performed either on primary tumors or metastasis, in particular lymph nodes (5/8, 62.5%), followed by lung (3/8, 37.5%) and liver (1/8, 12.5%) metastasis. CONCLUSION: Our results raise some important issues concerning the evaluation of PD-L1 in the "real-life" setting, providing strategies for its implementation.


Assuntos
Neoplasias Pulmonares , Neoplasias de Mama Triplo Negativas , Humanos , Imuno-Histoquímica , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Antígeno B7-H1/metabolismo , Neoplasias Pulmonares/patologia , Itália
9.
J Clin Oncol ; 42(8): 881-885, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38127722

RESUMO

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report the long-term results of the frontline trial with dasatinib and blinatumomab in induction/consolidation (GIMEMA LAL2116, D-ALBA) for adult Philadelphia-positive ALL (Ph+ ALL), which enrolled 63 patients of all ages. At a median follow-up of 53 months, disease-free survival, overall survival, and event-free survival are 75.8%, 80.7%, and 74.6%, respectively. No events have occurred among early molecular responders. A significantly worse outcome was recorded for IKZF1plus patients. Twenty-nine patients-93.1% being in molecular response (ie, complete molecular response or positive nonquantifiable) after dasatinib/blinatumomab-never received chemotherapy/transplant and continued with a tyrosine kinase inhibitor only; 28 patients remain in long-term complete hematologic response (CHR). An allogeneic transplant was carried out in first CHR mainly in patients with persistent minimal residual disease; 83.3% of patients are in continuous CHR. The transplant-related mortality was 12.5% for patients transplanted in first CHR and 13.7% overall. Nine relapses and six deaths have occurred. ABL1 mutations were found in seven cases. The final analysis of the D-ALBA study shows that a chemotherapy-free induction/consolidation regimen on the basis of a targeted strategy (dasatinib) and immunotherapy (blinatumomab) is effective in inducing durable long-term hematologic and molecular responses in adult Ph+ ALL, paving the way for a new era in the management of these patients.


Assuntos
Anticorpos Biespecíficos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Dasatinibe/efeitos adversos , Resultado do Tratamento , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico
10.
Cytopathology ; 35(1): 23-29, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37522315

RESUMO

Cystic lesions of the anterior head and neck region are a challenging and frequent finding on cytological smears. The scant amount of cellular material in cystic slides poses the greatest difficulty to interpretation, so that frequently they are diagnosed as inadequate or with minimal cellular component. Despite the majority of cystic lesions being benign, a minor portion consist of malignant cystic entities. In these latter cases, the evidence of very scant malignant cells can be misdiagnosed and/or underestimated, leading to a false negative diagnosis. Many papers have already described and detailed the range of possible benign and malignant cystic lesions in head and neck. In the current review we have focused on the less common entities that often lead to serious misinterpretation.


Assuntos
Citodiagnóstico , Humanos , Diagnóstico Diferencial
11.
Cancers (Basel) ; 15(18)2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37760449

RESUMO

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature concerning the immunogenicity of breast cancer has been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune response in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ subtypes, where increased TIL levels have been linked to a better response to neoadjuvant chemotherapy and improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes, and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10-30% of cases and is extremely variable based on tumor stage and molecular subtypes. Briefly, TNBC shows the highest percentage of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0-10% of cases) in hormone-receptor-positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points, and scoring systems have been utilized across published studies. In the present paper, an extensive review of the current knowledge of the immune landscape of BC is provided. TILS and PD-L1 expression across different BC subtypes are discussed, providing a guide for their pathological assessment and reporting.

12.
Diagnostics (Basel) ; 13(14)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37510131

RESUMO

BACKGROUND: Thyroid metastases (TMs) are a rare entity, ranging between 0 and 24% in the autopsy series. In the assessment of the best management, the discrimination between a primary and a metastatic thyroid lesion is crucial. In this regard, fine needle aspiration cytology (FNAC) is likely to play a crucial role especially when ancillary techniques (i.e., immunocytochemistry (ICC) and molecular testing) are carried out. METHODS: We searched for all the TMs diagnosed using FNAC and analyzed between 2014 and 2023. The cases were processed with liquid-based (LBC) and ICC and molecular testing performed on LBC-stored material. RESULTS: We reported 2.2% (19 cases) of TMs out of 1022 malignancies. TMs included: 1 larynx carcinoma (LX-Ca), 1 melanoma, 2 breast carcinomas (B-Ca), 3 lung carcinomas (LG-Ca), 4 gastro-intestinal carcinomas (GI-Ca), and 8 clear cell renal carcinomas (CCRC). All patients had a previous cancer history, between 300 and 2 months from the primary cancers. The morphological features were supported by ICC, which were contributive in 100% of cases. All TMs cases were characterized by multiple thyroid nodules except the melanoma case. Four cases underwent total thyroidectomy (1 B, 1 LX, 1 melanoma, and 1 CCRC) whilst 15 TMs were treated with radio-chemotherapy. CONCLUSIONS: FNAC empowered the diagnostic workup of patients with TMs avoiding useless surgery. The low sensitivity of cytology might be reinforced by the application of ancillary techniques. We found a predominant rate of kidney metastatic carcinomas, followed by lung and breast. TMs are frequently multifocal and in a context of a systemic disease so a tailored therapy seems to be the best treatment.

14.
J Pers Med ; 13(6)2023 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-37373937

RESUMO

Primary mucinous cystadenocarcinoma (MCA) is a rare breast carcinoma subtype showing overlapping histopathological features with mucinous cystadenocarcinoma of the ovary and pancreas. Current literature data suggest a favorable prognosis of breast MCAs despite its immunoprofile usually revealing lack of expression of estrogen receptor, progesterone receptor and HER-2 and high Ki67. As far as we know, only 36 cases have been reported in the literature to date. Its ambiguous morpho-phenotypic profile makes histological diagnosis very challenging. It must be distinguished from typical mucin-producing breast carcinomas and, above all, metastases from the same histotype in other sites (ovary, pancreas, appendix). Herein, we report the case of a primary breast MCA occurring in a 41-year-old female with peculiar histological features.

15.
Cytopathology ; 34(6): 542-550, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37377125

RESUMO

Cystic lesions of the salivary glands are very uncommon entities. However, on occasion, some neoplasms of the salivary glands show a cystic component, which may be predominant or only partially cystic. Basal cell adenoma, canalicular adenoma, oncocytoma, sebaceous adenoma, intraductal papilloma, epithelial-myoepithelial carcinoma, intraductal carcinoma, and secretory carcinoma are such cystic entities. Cystic degeneration and necrosis, which can develop within solid tumours, represent another possibility. The ability to recognise this type of lesion is a challenge in diagnostic cytology because hypocellular fluid is frequently recovered. Furthermore, evaluating all of the differential diagnoses for cystic lesions of the salivary glands is helpful in obtaining the correct diagnosis. Herein, we evaluate the various types of cystic lesions within the salivary glands.

16.
Cancers (Basel) ; 15(9)2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37173916

RESUMO

BACKGROUND: The diffusion of screening programs has resulted in a decrease of cT4 breast cancer diagnosis. The standard care for cT4 was neoadjuvant chemotherapy (NA), surgery, and locoregional or adjuvant systemic therapies. NA allows two outcomes: 1. improve survival rates, and 2. de-escalation of surgery. This de-escalation has allowed the introduction of conservative breast surgery (CBS). We evaluate the possibility of submitting cT4 patients to CBS instead of radical breast surgery (RBS) by assessing the risk of locoregional disease-free survival, (LR-DFS) distant disease-free survival (DDFS), and overall survival (OS). METHODS: This monocentric, retrospective study evaluated cT4 patients submitted to NA and surgery between January 2014 and July 2021. The study population included patients undergoing CBS or RBS without immediate reconstruction. Survival curves were obtained using the Kaplan-Meyer method and compared using a Log Rank test. RESULTS: At a follow-up of 43.7 months, LR-DFS was 70% and 75.9%, respectively, in CBS and RBS (p = 0.420). DDFS was 67.8% and 29.7%, respectively, (p = 0.122). OS was 69.8% and 59.8%, respectively, (p = 0.311). CONCLUSIONS: In patients with major or complete response to NA, CBS can be considered a safe alternative to RBS in the treatment of cT4a-d stage. In patients with poor response to NA, RBS remained the best surgical choice.

17.
Diagnostics (Basel) ; 13(7)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37046442

RESUMO

BACKGROUND: Spontaneous regression of tumors is a rare phenomenon in which cancer volume is reduced or, alternatively, a tumor completely disappears in the absence of any pharmacological treatment. This phenomenon has previously been described in several tumors, such as neuroblastomas, testicular malignancies, renal cell carcinomas, melanomas, and lymphomas. Spontaneous remission has also been documented in breast cancer; however, it represents an extremely rare and poorly understood phenomenon, with only a few reported cases in the literature. METHODS: We herein report two cases of breast cancer that showed spontaneous tumor regression in the surgical specimen after a pathologically confirmed diagnosis of invasive breast cancer in core needle biopsy samples. RESULTS: Macroscopically, both the surgical samples revealed a whitish, fibrous area with a rubbery consistency. On histological examination, diffuse fibrous tissue, hemosiderin deposition, and chronic inflammation were observed. The first case showed the complete disappearance of the tumor, whereas the second case showed just a small (3 mm), residual nest of neoplastic cells. CONCLUSIONS: Although spontaneous regression of breast cancer is a rare event, it is important to know that it might happen. It is also of great importance to try to better explain, over time, its underlying mechanism. This knowledge could help us to further develop cancer prevention methods and predict the clinical course of these kinds of neoplasms.

18.
Cancers (Basel) ; 15(7)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37046707

RESUMO

(1) Background: To help to refine the accuracy of sentinel lymph node biopsy (SLNB) in breast cancer (BC) patients with biopsy-proven nodal disease prior to neoadjuvant chemotherapy (NACT), a method of marking the biopsy-proven positive LN at diagnosis to enable its removal during surgery was proposed. The aim of this study was to evaluate the accuracy of the Radio-Guided Occult Lesion Localization (ROLL) technique of biopsy-proven metastatic LN in nodal staging after NACT among node-positive BC patients. (2) Methods: Patients with invasive BC and biopsy-proven axillary metastases receiving NACT were enrolled. A clip marker was placed on the sampled LN (clipped lymph node, CLN) before NACT. Before surgery, the ROLL procedure (radioactive tracer injection into CLN under ultrasound guidance) was performed, and the CLN was surgically resected. The correspondence between the CLNs and SLNs was evaluated. The pathologic findings of the CLNs and SLN(s) were compared with remaining axillary nodes at ALND to determine false negative rates (FNRs). (3) Results: Seventy-two patients were analyzed. Surgery successfully identified the CLN in 70/72 procedures (97.2%). For 60/72 patients who underwent ALND, the FNRs dropped from 19.35% for SLNB to 3.13% for CLN biopsy. (4) Conclusions: The ROLL procedure got CLNs is accurate in axillary nodal staging after NACT in node-positive BC patients at diagnosis.

19.
Ann Hematol ; 102(5): 1099-1109, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36959485

RESUMO

Mixed-phenotype acute leukemia (MPAL) is a rare disease. Treatment is often similar to that of acute lymphoblastic leukemia (ALL), but the outcome in adults and the role of allogeneic stem cell transplantation (AlloSCT) are not well defined. We report on 77 adult patients diagnosed with MPAL over the last 10 years and treated with a curative intent. Median age was 49 years; 7.6% of cases had a BCR::ABL1 rearrangement. Thirty patients (39%) were treated with an acute myeloid leukemia (AML)-like induction and 47 (61%) with an ALL-like scheme. The complete remission (CR) rate was 67.6% and an ALL-like therapy was associated with a better CR rate (P = 0.048). The median OS was 41.9 months; age ≤ 60 years was associated with a better OS (67 vs 26 months, P = 0.014). An AlloSCT was performed in 50 patients (65%). The 5-year OS of transplanted patients was 54%. The OS post-AlloSCT was better in patients who were minimal residual disease (MRD)-negative prior to transplant (75.8% vs 45.2%, P = 0.06). This study shows that MPAL patients respond better to an ALL-like induction therapy; that consolidation therapy should include, whenever possible, an AlloSCT and that MRD negativity should be a primary endpoint of treatment.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Doença Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Fenótipo , Estudos Retrospectivos
20.
Ann Hematol ; 102(4): 769-775, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36795117

RESUMO

Gemtuzumab ozogamicin (GO), is an anti-CD33 monoclonal antibody, approved for AML CD33 + , those patients with low and intermediate-risk who obtain a complete response may also be candidated for consolidation with autologous stem cell transplantation (ASCT). However, there are scant data on the mobilization of hemopoietic stem cells (HSC) after fractionated GO. We retrospectively studied data from five Italian centers and identified 20 patients (median age 54 years, range 29-69, 15 female, 15 NPM1mutated) that attempted HSC mobilization after fractionated doses of GO + "7 + 3" regimen and 1-2 cycles of consolidation (GO + HDAC + daunorubicin). After chemotherapy and standard G-CSF, 11/20 patients (55%) reached the threshold of 20 CD34 + /µL, and HSC were successfully harvested, while 9 patients (45%) failed. The median day of apheresis was Day + 26 from the start of chemotherapy (range 22-39 days). In good mobilizer patients, the median circulating CD34 + cells were 35.9 cells/µL and the median CD34 + harvested were 4.65 × 106/kg of patients' body weight. With a median follow-up of 12.7 months, at 24 months from the first diagnosis, 93.3% of all 20 patients were alive and the median overall survival was 25 months. The 2-year RFS rate from the timepoint of the first CR was 72.6%, while the median RFS was not reached. However, only five patients underwent ASCT and achieved full engraftment.In conclusion, in our cohort of patients, the addition of GO reduced HSC mobilization and harvesting, which was reached in about 55% of patients. Nevertheless, further studies are warranted to evaluate the effects of fractionated doses of GO on HSC mobilization and ASCT outcomes.


Assuntos
Gemtuzumab , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adulto , Feminino , Humanos , Antígenos CD34 , Gemtuzumab/uso terapêutico , Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Estudos Retrospectivos , Transplante Autólogo , Masculino , Pessoa de Meia-Idade , Idoso
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