RESUMEN
OBJECTIVES: To describe the natural history of AML, the clinical results and the need for treatment during long-term follow-up of renal AML. METHODS: Retrospective study of patients diagnosed with AML by computed tomography or nuclear magnetic resonance between 2001 and 2019, with at least two follow-up images. Clinical and imaging variables, need for intervention, complications and follow-up time were recorded. Statistical analysis was performed using SPSS 22.0. RESULTS: 111 patients and 145 AML were included. The median follow-up was 6.17 years (range 0.7-18.1, IQR 11.8-12.2). The median tumor size at diagnosis was 13 mm (IQR 7.5-30), with 24 (16.4%) being ≥ 4 cm. Most presented as an incidental finding (85.5%); in 3 (2.1%) cases, the presentation was as a spontaneous retroperitoneal hematoma. The main indication for intervention was size ≥ 4 cm in 50%. Eighteen (12%) patients received a first intervention, being urgent in 3. Embolization was performed in 15 cases and partial nephrectomy in 3. The need for reintervention was recorded in five: two underwent partial nephrectomy and two total nephrectomy; one patient required a new urgent embolization. Of the non-operated patients, 43% decreased in size or did not change, while 57% increased, with the median annual growth being 0.13 mm (IQR - 0.11 to 0.73). There were no differences in the median growth in tumors measuring ≥ 4 cm (0.16 mm) at diagnosis vs. < 4 cm (0.13 mm) (p = 0.9). CONCLUSIONS: The findings of this study suggest that AML typically demonstrate a slow-progressing clinical course during long-term follow-up. Moreover, our observations, which cast doubt on tumor size as a reliable predictor of adverse clinical outcomes, advocate for a less intensive monitoring strategy in both monitoring frequency and choice of imaging modality.
Asunto(s)
Angiomiolipoma , Embolización Terapéutica , Neoplasias Renales , Leucemia Mieloide Aguda , Humanos , Angiomiolipoma/diagnóstico por imagen , Angiomiolipoma/cirugía , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Estudios de Seguimiento , Estudios Retrospectivos , Nefrectomía/métodos , Embolización Terapéutica/métodos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/cirugíaRESUMEN
BACKGROUND In t(8;21) acute myeloid leukemia (AML), patients with extramedullary infiltration (EMI) tend to have worse survival outcomes than those without EMI. However, it is still unclear whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) benefits EMI-positive t(8;21) AML patients. MATERIAL AND METHODS This study retrospectively enrolled 651 t(8;21) AML patients, and analyzed 51 patients with EMI at diagnosis. Among the 51 patients, 15 patients received allo-HSCT. RESULTS The incidence of EMI in t(8;21) AML was 10.0%, and the first complete remission rate was 78.5% in EMI-positive t(8;21) AML patients. The central nervous system was the most frequently involved site (29.4%), followed by bones (15.7%), and skin (9.8%). In terms of karyotype, 19 (37.3%) patients were t(8;21) alone, 12 (23.5%) had additional loss of a sex chromosome, and 5 (9.8%) had complex karyotype. Significantly better overall survival was observed in patients with allo-HSCT compared to patients without allo-HSCT in both multivariable models (HR=0.32; P=0.0122) and the Kaplan-Meier curves (P=0.0157). CONCLUSIONS Allo-HSCT improved the survival of EMI-positive t(8;21) AML.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Estudios Retrospectivos , Trasplante Homólogo/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/cirugía , Pronóstico , Trasplante de Células Madre Hematopoyéticas/métodosRESUMEN
Recent developments in chemotherapy for gynecologic malignancies have improved treatment results in patients and promoted long-term survival. However, various adverse events caused by long-term chemotherapy are still being observed. Here, we report a case of myelodysplastic syndrome that developed during chemotherapy for recurrent ovarian cancer and progressed to acute myeloid leukemia. However, chemotherapy for ovarian cancer was continued while maintaining the quality of life under certain conditions, such as maintenance of platelet levels in collaboration with a hematologist. A 69- year-old woman(gravida 3, para 2)was diagnosed with stage â ¢C ovarian cancer in our department. After 6 cycles of preoperative chemotherapy with paclitaxel plus carboplatin plus bevacizumab(TC plus Bev), we performed a simple abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, sigmoid colon resection, and low anterior resection. Postoperatively, 3 cycles of TC plus Bev and 6 cycles of Bev monotherapy were completed for stage â ¢C ovarian cancer (ypT3cNXM0, high-grade serous carcinoma). However, the cancer recurred, and the patient received 3 cycles of gemcitabine plus Bev and 3 cycles of doxorubicin plus Bev. Precursor cells and prolonged neutropenia were observed, and myelodysplastic syndrome was diagnosed. One month later, the condition progressed to acute myeloid leukemia. The patient's neutrophil count recovered spontaneously, and subsequently, 7 cycles of weekly paclitaxel plus Bev therapy were completed along with symptomatic treatment. Unfortunately, she died of septic shock against the background of acute myeloid leukemia. It is important to monitor the appearance of blasts for early detection of therapy-related myelodysplastic syndromes occurring during chemotherapy, as in the case in this report. Additionally, it is important to maintain platelet count and continue chemotherapy for the primary disease.
Asunto(s)
Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Neoplasias Ováricas , Humanos , Femenino , Anciano , Calidad de Vida , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Bevacizumab , Paclitaxel , Carboplatino , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/cirugía , Síndromes Mielodisplásicos/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
BACKGROUND: Angiomyolipomas (AML) represent less than 10% of renal tumours. They are most often detected incidentally during imaging tests, but there are several histological variants that pose difficulties in the radiological differential diagnosis. Their identification should allow the loss of renal parenchyma due to embolization or radical surgery to be prevented. METHODS: Retrospective study of patients undergoing kidney surgery with post-surgical pathological diagnosis of AML at the Álvaro Cunqueiro Hospital (2016-2021). Patients with a radiological diagnosis of AML who underwent surgery based on clinical criteria were excluded. RESULTS: 18 patients were registered, allowing for the assessment of 18 renal tumours. All of the cases were diagnosed incidentally. Preoperative radiological diagnosis was: 9 lesions suggestive of renal cell carcinoma (RCC) (50%), 7 cases suggestive of RCC vs. AML (38.9%) and 2 lesions suggestive of AML vs. retroperitoneal liposarcoma (11.1%). Histological variants of AML were found in 61.1% of cases (n = 11). The most widely used surgical technique was partial nephrectomy, in 66.67% of cases. CONCLUSIONS: The radiological differential diagnosis of AML, and particularly its variants, with malignant lesions have important limitations either due to the predominance or scarcity of any of the AML components. Some cases can also pose difficulties at the histological level. This fact highlights the importance of the specialization of uroradiologists and uropathologists and the performance of kidney-sparing therapeutic techniques.
Asunto(s)
Angiomiolipoma , Carcinoma de Células Renales , Neoplasias Renales , Leucemia Mieloide Aguda , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/cirugía , Carcinoma de Células Renales/cirugía , Angiomiolipoma/diagnóstico , Angiomiolipoma/terapia , Estudios Retrospectivos , Nefrectomía/métodos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/cirugía , Diagnóstico DiferencialRESUMEN
Pulmonary complications may occur after hematopoietic stem cell transplantation for hematologic malignancies. Lung transplantation is the only treatment option for end-stage lung failure. We presented a case of acute myeloid leukemia who received a hematopoietic stem cell transplantation and underwent bilateral lung transplantation with end-stage usual interstitial pneumonia and chronic obstructive lung disease. This case showed that lung transplantation could be successfully applied in properly selected hematologic malignancy patients with long disease-free survival, like lung transplantations performed for other indications.
Asunto(s)
Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Trasplante de Pulmón , Humanos , Trasplante Homólogo/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mieloide Aguda/cirugía , Neoplasias Hematológicas/terapia , Trasplante de Pulmón/efectos adversos , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
Angiomyolipoma (AML) complicated with tumour thrombus extending to the confluence of inferior vena cava (IVC) with right atrium is rarely observed. We report a female AML patient admitted to our centre on January 21, 2020, with complication of tumour thrombus extending to the confluence of IVC with right atrium and had no sign of difficult breathing. She underwent whole-abdominal enhanced CT for abdominal pain and was diagnosed with a possible renal AML with tumour thrombus. Open radical nephrectomy and thrombectomy of vena cava were performed. Intraoperative transoesophageal echocardiography indicated that the tumour thrombus has reached the confluence of IVC with right atrium. The operation took 255 min with an intraoperative haemorrhage of 800mL. The patient was discharged 7 days after surgery. Pathology revealed lipoma-like AML. Immunohistochemistry showed vimentin (+), EMA (-), HMB45 (+), S-100 (-), SMA (+), TFE-3 (-), melan A (+). After 2 years of follow-up, we found that the patient showed full recovery and had no recurrence. Therefore, lipoma-like AML should also be followed closely for recurrence and metastasis. When AML involves IVC tumour thrombus, open thrombectomy and radical nephrectomy are safe and effective methods.
Asunto(s)
Angiomiolipoma , Carcinoma de Células Renales , Neoplasias Renales , Leucemia Mieloide Aguda , Lipoma , Trombosis , Trombosis de la Vena , Humanos , Femenino , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/cirugía , Vena Cava Inferior/patología , Carcinoma de Células Renales/cirugía , Angiomiolipoma/complicaciones , Angiomiolipoma/diagnóstico por imagen , Angiomiolipoma/cirugía , Neoplasias Renales/complicaciones , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Trombosis/diagnóstico por imagen , Trombosis/cirugía , Trombosis/complicaciones , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/etiología , Trombosis de la Vena/cirugía , Trombectomía/efectos adversos , Nefrectomía/métodos , Lipoma/complicaciones , Lipoma/diagnóstico por imagen , Lipoma/cirugía , Atrios Cardíacos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/cirugíaRESUMEN
An 18-year-old girl with high-risk acute myeloid leukemia developed Streptococcus mitis septic shock and multiorgan dysfunction syndrome, including biventricular failure. Due to the anticipated reversibility of her cardiogenic shock, her young age, and her favorable survival chance after an allogeneic hematopoietic stem cell transplant, she was placed on full circulatory support with venoarterial extracorporeal membrane oxygenation as a bridge to her successful hematopoietic stem cell transplantation 2 months later. This highlights the importance of prognostication in patient selection for extracorporeal life support. A multidisciplinary approach is essential to each case until more definite initiation criteria, risk stratification, and treatment protocols are established.
Asunto(s)
Trasplante de Médula Ósea , Oxigenación por Membrana Extracorpórea , Leucemia Mieloide Aguda , Choque Cardiogénico , Adolescente , Femenino , Humanos , Insuficiencia Cardíaca , Leucemia Mieloide Aguda/cirugía , Leucemia Mieloide Aguda/terapia , Choque Cardiogénico/etiología , Choque Cardiogénico/terapiaRESUMEN
Although alternative donors extend transplant access, whether recipient ancestry affects the time to allogeneic transplant is not established. We analyzed the likelihood of clinically significant delays to allograft by patient ancestry in 313 adult patients with acute myelogenous leukemia (AML) who underwent transplantation. Non-European ancestry patients (n = 99) were more likely than Europeans (n = 214) to receive HLA-mismatched donor allografts (45% vs 24%). Overall, the median time from transplant indication to allograft was 127 days (range, 57-1683). In multivariable analysis, non-Europeans had an increased risk of prolonged indication to transplant time >180 days owing to significant delays in indication to consult >90 days and consult to transplant >120 days. Compared with recipients of HLA-matched unrelated donors (URDs), HLA-mismatched adult donor recipients were at an increased risk of delayed indication to transplant, whereas HLA-identical sibling and cord blood recipients were at a lower risk. Subanalysis showed more indication to transplant delays >180 days in non-European (44%) vs European (19%) 8/8 URD recipients. Finally, the pandemic further exacerbated delays for non-Europeans. In summary, although non-European patients with AML are less likely to receive 8/8 URDs as expected, if they do, their transplants are delayed. HLA-identical siblings and cord blood facilitate the fastest transplants regardless of patient ancestry, whereas other adult donor transplants are delayed. Strategies to mitigate referral barriers, hasten donor evaluation, and use all alternative donor sources are critical to ensure timely transplantation for patients with AML.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Adulto , Leucemia Mieloide Aguda/cirugía , Trasplante Homólogo , Donante no Emparentado , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Accesibilidad a los Servicios de SaludRESUMEN
Angiomyolipomas (AMLs) are mesenchymal tumours derived from perivascular epithelioid cells. Although AMLs are generally known as benign and extremely rare epithelioid variants of AML, they may be potentially aggressive. Here we present an adrenal epithelioid AML and the literature review. A 64-year-old female patient was diagnosed with a left adrenal mass detected incidentally on ultrasonography. Preoperative abdominal CT (computed tomography) showed a 95×68 mm heterogeneous contrast enhancement mass lesion in the left adrenal gland. The lesion was hormone inactive in the endocrinological evaluation, and left laparoscopic adrenalectomy was performed. The patient was discharged on the 2nd postoperative day. Pathology was reported as epithelioid subtype AML. The patient has no local recurrence or metastasis in the 18-month follow-up period and imaging. Adrenal epithelioid AML is an extremely rare and potentially aggressive variant. According to the literature, open or laparoscopic adrenalectomy seems to be suitable option for disease management.
Asunto(s)
Angiomiolipoma , Leucemia Mieloide Aguda , Glándulas Suprarrenales/patología , Adrenalectomía , Angiomiolipoma/diagnóstico , Angiomiolipoma/patología , Angiomiolipoma/cirugía , Femenino , Hormonas , Humanos , Leucemia Mieloide Aguda/cirugía , Persona de Mediana EdadRESUMEN
The prognosis of relapsed/refractory (R/R) pediatric acute leukemia is extremely poor. We retrospectively reviewed 20 consecutive pediatric patients with R/R acute leukemia who underwent a first HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning (haplo-RIC-PBSCT) with very low-dose antithymocyte globulin (ATG) between 2012 and 2019. Of these 20 patients, 7 patients had acute lymphoblastic leukemia, and 13 had acute myeloid leukemia. At the time of haplo-RIC-PBSCT, 15 patients had active disease. The median follow-up duration for survivors was 56 months (range 22-108 months). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, short-term methotrexate, methylprednisolone, and ATG 1.25 mg/kg on day-2. The 2-year cumulative incidence of transplant-related mortality and relapse were 5.0% [95% confidence interval (CI) 0.7-30.5%)] and 57.8% (95% CI 37.4-79.6%), respectively. Among the 20 patients, 16 (80.0%) developed grade III-IV acute GVHD, and 2 developed severe chronic GVHD. The 2-year event-free survival and overall survival rates were 40.0% (95% CI 19.3-60.0%) and 50.0% (95% CI 27.1-69.2%), respectively. Although the sample size is small, the survival outcomes of the present study are encouraging.
Asunto(s)
Suero Antilinfocítico/administración & dosificación , Antígenos HLA/genética , Haploidia , Leucemia Mieloide Aguda/cirugía , Trasplante de Células Madre de Sangre Periférica/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Acondicionamiento Pretrasplante/métodos , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Lactante , Leucemia Mieloide Aguda/mortalidad , Masculino , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: The mixed-lineage leukemia (MLL) gene is located on chromosome 11q23. The MLL gene can be rearranged to generate partial tandem duplications (MLL-PTD), which occurs in about 5-10% of acute myeloid leukemia (AML) with a normal karyotype and in 5-6% of myelodysplastic syndrome (MDS) patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently one of the curative therapies available for AML and MDS with excess blasts (MDS-EB). However, how the prognosis of patients with high levels of MLL-PTD after allo-HSCT, and whether MLL-PTD could be used as a reliable indicator for minimal residual disease (MRD) monitoring in transplant patients remains unknown. Our study purposed to analyze the dynamic changes of MLL-PTD peri-transplantation and the best threshold for predicting relapse after transplantation. METHODS: We retrospectively collected the clinical data of 48 patients with MLL-PTD AML or MDS-EB who underwent allo-HSCT in Peking University People's Hospital. The MLL-PTD was examined by real-time quantitative polymerase chain reaction (RQ-PCR) at the diagnosis, before transplantation and the fixed time points after transplantation. Detectable MLL-PTD/ABL > 0.08% was defined as MLL-PTD positive in this study. RESULTS: The 48 patients included 33 AML patients and 15 MDS-EB patients. The median follow-up time was 26(0.7-56) months after HSCT. In AML patients, 7 patients (21.2%) died of treatment-related mortality (TRM), 6 patients (18.2%) underwent hematological relapse and died ultimately. Of the 15 patients with MDS-EB, 2 patients (13.3%) died of infection. The 3-year cumulative incidence of relapse (CIR), overall survival (OS), disease-free survival (DFS) and TRM were 13.7 ± 5.2, 67.8 ± 6.9, 68.1 ± 6.8 and 20.3% ± 6.1%, respectively. ROC curve showed that post-transplant MLL-PTD ≥ 1.0% was the optimal cut-off value for predicting hematological relapse after allo-HSCT. There was statistical difference between post-transplant MLL-PTD ≥ 1.0% and MLL-PTD < 1.0% groups (3-year CIR: 75% ± 15.3% vs. 0%, P < 0.001; 3-year OS: 25.0 ± 15.3% vs. 80.7% ± 6.6%, P < 0.001; 3-year DFS: 25.0 ± 15.3% vs. 80.7 ± 6.6%, P < 0.001; 3-year TRM: 0 vs. 19.3 ± 6.6%, P = 0.277). However, whether MLL-PTD ≥ 1% or MLL-PTD < 1% before transplantation has no significant difference on the prognosis. CONCLUSIONS: Our study indicated that MLL-PTD had a certain stability and could effectively reflect the change of tumor burden. The expression level of MLL-PTD after transplantation can serve as an effective indicator for predicting relapse.
Asunto(s)
N-Metiltransferasa de Histona-Lisina/genética , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicos/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Recurrencia Local de Neoplasia/genética , Proteínas de Fusión Oncogénica/genética , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Reordenamiento Génico/genética , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/cirugía , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/cirugía , Recurrencia Local de Neoplasia/mortalidad , Neoplasia Residual , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Pronóstico , Supervivencia sin Progresión , Recurrencia , Estudios Retrospectivos , Trasplante Homólogo , Carga Tumoral/genéticaRESUMEN
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the preferred treatment for children with high-risk hematologic malignancies, but post-allo-HSCT relapse has a poor prognosis and limited treatment options. We evaluated the feasibility, outcome, and risk factors influencing survival after T-cell-replete haploidentical HSCT with low-dose anti-thymocyte globulin (ATG) in 30 patients with post-allo-HSCT relapse of acute lymphoblastic leukemia and acute myeloid leukemia. Overall, 50% of the patients had complete remission (CR) before the second transplant and the overall survival (OS) rate was 52%. In surviving patients (median follow-up 614 days), Kaplan-Meier analysis revealed estimated 2-year leukemia-free survival and OS rates of 48.1% and 61.1%, respectively. Cumulative incidences of 2-year non-relapse mortality and relapse were 24.7% and 36.3%, respectively. Achieving CR before the second allo-HSCT was a predominant independent prognostic factor identified in the multivariate analysis, with a significantly improved 2-year OS rate of 86.7%. T-cell-replete haplo-HSCT with low-dose ATG for second allo-HSCT may benefit a selected patient population.
Asunto(s)
Suero Antilinfocítico/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/cirugía , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Reoperación/métodos , Linfocitos T/trasplante , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Estudios de Factibilidad , Femenino , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Lactante , Leucemia Mieloide Aguda/mortalidad , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Recurrencia , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
We present a case of acute myeloid leukemia developing acute graft-versus-host-disease (GVHD) in the post transplant phase. The patient had GVHD of skin, liver and gastro-intestinal tract (resolved) with polymicrobial sepsis. The clinical course, treatment and pathological findings on autopsy including the cause of death have been discussed.
Asunto(s)
Causas de Muerte , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/fisiopatología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Leucemia Mieloide Aguda/cirugía , Trasplante Homólogo/efectos adversos , Adulto , Autopsia/estadística & datos numéricos , Resultado Fatal , Humanos , MasculinoRESUMEN
PURPOSE OF REVIEW: With the recent approval of multiple new drugs for the treatment of acute myeloid leukemia (AML), the relevance of conventional treatment approaches, such as daunorubicin and cytarabine ("3+7") induction chemotherapy, has been challenged. We review the AML risk stratification, the efficacy of the newly approved drugs, and the role of "3+7". RECENT FINDINGS: Treatment of AML is becoming more niched with specific subtypes more appropriately treated with gemtuzumab, midostaurin, and CPX-351. Although lower intensity therapies can yield high response rates, they are less efficient at preventing relapses. The only curative potential for poor-risk AML is still an allogeneic stem cell transplant. The number of AML subtypes where 3+7 alone is an appropriate therapeutic option is shrinking. However, it remains the backbone for combination therapy with newer agents in patients suitable for intensive chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Citarabina/uso terapéutico , Daunorrubicina/uso terapéutico , Gemtuzumab/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Humanos , Quimioterapia de Inducción , Leucemia Mieloide Aguda/clasificación , Leucemia Mieloide Aguda/cirugía , Medición de Riesgo , Estaurosporina/análogos & derivados , Estaurosporina/uso terapéuticoRESUMEN
PURPOSE: The anti-leukemic activity of allogeneic hematopoietic cell transplantation (HCT) depends on both the intensity of conditioning regimen and the strength of the graft-versus-leukemia (GVL) effect. However, it is unclear whether the sensitivity of the GVL effects differs between donor type and graft source. EXPERIMENTAL DESIGN: We retrospectively evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on transplant outcomes for adults with acute leukemia (n = 6,548) between 2007 and 2017 using a Japanese database. In all analyses, we separately evaluated three distinct cohorts based on donor type [(8/8 allele-matched sibling donor, 8/8 allele-matched unrelated donor, and unrelated single-cord blood (UCB)]. RESULTS: The multivariate analysis, in which the development of GVHD was treated as a time-dependent covariate, showed a reductive effect of grade I-II acute GVHD on treatment failure (defined as 1-leukemia-free survival; P < 0.001), overall mortality (OM; P < 0.001), relapse (P < 0.001), and non-relapse mortality (NRM; P < 0.001) in patients receiving from UCB. A reductive effect of limited chronic GVHD on treatment failure (P < 0.001), OM (P < 0.001), and NRM (P < 0.001) was also shown in patients receiving from UCB. However, these effects were not always shown in patients receiving from other donors. The beneficial effects of mild acute and chronic GVHD after UCB transplantation on treatment failure were noted relatively in subgroups of patients with acute myelogenous leukemia and a non-remission status. CONCLUSIONS: These data suggested that the development of mild GVHD could improve survival after UCB transplantation for acute leukemia.
Asunto(s)
Enfermedad Injerto contra Huésped/mortalidad , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/cirugía , Complicaciones Posoperatorias/mortalidad , Enfermedad Aguda , Adulto , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Donantes de TejidosRESUMEN
Despite the ability of combination antiretroviral therapy (cART) to increase the life expectancy of patients infected with human immunodeficiency virus (HIV), viral reservoirs persist during life-long treatment. Notably, two cases of functional cure for HIV have been reported and are known as the "Berlin Patient" and the "London Patient". Both patients received allogeneic hematopoietic stem cell transplantation from donors with homozygous CCR5 delta32 mutation for an associated hematological malignancy. Therefore, there is growing interest in creating an HIV-resistant immune system through the use of gene-modified autologous hematopoietic stem cells with non-functional CCR5. Moreover, studies in CXCR4-targeted gene therapy for HIV have also shown great promise. Developing a cure for HIV infection remains a high priority. In this review, we discuss the increasing progress of coreceptor-based hematopoietic stem cell gene therapy, cART, milder conditioning regimens, and shock and kill strategies that have important implications for designing potential strategies aiming to achieve a functional cure for the majority of people with HIV.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Terapia Genética , Infecciones por VIH/terapia , VIH/inmunología , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/cirugía , Leucemia Mieloide Aguda/cirugía , Animales , Fármacos Anti-VIH/efectos adversos , Selección de Donante , Terapia Genética/efectos adversos , Alemania , VIH/patogenicidad , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/virología , Homocigoto , Interacciones Huésped-Patógeno , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/virología , Donadores Vivos , Londres , Mutación , Receptores CCR5/genética , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are usually associated with poor outcomes, especially in high-risk AML/MDS. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for patients suffering from high-risk AML/MDS. However, many patients relapse after allo-HSCT. Novel therapy to prevent relapse is urgently needed. Both the BCL-2 inhibitor venetoclax (VEN) and the hypomethylating agent decitabine (DEC) possess significant antitumor activity effects against AML/MDS. Administration of DEC has been shown to ameliorate graft-versus-host disease (GVHD) and boost the graft-versus-leukemia (GVL) effect post-transplantation. We therefore conducted a prospective study (ChiCTR1900025374) to examine the tolerability and efficacy of a maintenance therapy of low-dose decitabine (LDEC) plus VEN to prevent relapse after allo-HSCT for high-risk AML/MDS patients. Twenty patients with high-risk AML (n = 17) or high-risk MDS (n = 3) post-transplantation were recruited. Approximately day 100 post-transplantation, all patients received LDEC (15 mg/m2 for 3 d) followed by VEN (200 mg) on d 1-21. The cycle interval was 2 mo, and there was 10 cycles. The primary end points of this study were rates of overall survival (OS) and event-free survival (EFS). The secondary endpoints included adverse events (AEs), cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), incidences of acute GVHD (aGVHD) and chronic GVHD (cGVHD), and incidences of viral infection after allo-HSCT. Survival outcomes were assessed using Kaplan-Meier analysis. The median follow-up was 598 (149-1072) d. Two patients relapsed, 1 died, and 1 is still alive after the second transplant. The 2-y OS and EFS rates were 85.2% and 84.7%, respectively. The median 2-y EFS time was 525 (149-1072) d, and 17 patients still had EFS and were alive at the time of this writing. The most common AEs were neutropenia, anemia, thrombocytopenia, neutropenic fever, and fatigue. Grade 2 or 3 AEs were observed in 35% (7/20) and 20% (4/20) of the patients, respectively. No grade >3 AEs were observed. aGVHD (any grade) and cGVHD (limited or extensive) occurred in 55% and 20% of patients, respectively. We conclude that LDEC + VEN can be administered safely after allo-HSCT with no evidence of an increased incidence of GVHD, and this combination decreases the relapse rate in high-risk AML/MDS patients. This novel maintenance therapy may be a promising way to prevent relapse in high-risk AML/MDS patients.
Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Decitabina/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/cirugía , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/cirugía , Sulfonamidas/efectos adversos , Acondicionamiento Pretrasplante/métodos , Adulto , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Decitabina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Prospectivos , Recurrencia , Sulfonamidas/administración & dosificación , Trasplante Homólogo/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: The optimal conditioning regimen in cord blood transplantation (CBT) needs to be determined. This study aimed to identify the impact of conditioning regimen on the outcome of CBT in children with acute leukemia. METHODS: Medical records of patients with acute leukemia who received CBT were retrospectively reviewed. RESULTS: A total of 71 patients were allocated into 2 groups; patients who received total body irradiation 10 Gy, cyclophosphamide 120 mg/kg, and fludarabine 75 mg/m² were named as TCF group (n = 18), while the non-TCF group (n = 53) included patients conditioned with regimens other than the TCF regimen. All patients in the TCF group were successfully engrafted, while 22.6% in the non-TCF group (n = 12) failed to achieve donor-origin hematopoiesis (P = 0.028). The incidence of cytomegalovirus diseases was 5.6% in the TCF group and 30.2% in the non-TCF group (P = 0.029). The 5-year overall survival rates of the TCF and non-TCF groups were 77.8% and 44.2%, respectively (P = 0.017). CONCLUSION: Patients conditioned with the TCF regimen achieved better engraftment and survival rates, less suffering from cytomegalovirus disease. Our data suggest that the TCF regimen is a preferred option for CBT in children with acute leukemia.
Asunto(s)
Antineoplásicos/uso terapéutico , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Ciclofosfamida/uso terapéutico , Inmunosupresores/uso terapéutico , Leucemia Mieloide Aguda/cirugía , Vidarabina/análogos & derivados , Irradiación Corporal Total , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Tasa de Supervivencia , Acondicionamiento Pretrasplante , Resultado del Tratamiento , Vidarabina/uso terapéuticoRESUMEN
BACKGROUND: Acute myeloid leukemia (AML) is a hematological malignancy originating from myeloid precursor cells, with different cytogenetic abnormalities, genetic mutations and diverse clinical prognoses. We investigated the clinical characteristics, treatment patterns, and outcomes of adult AML patients in Taiwan. MATERIALS AND METHODS: We retrospectively included 3851 patients with AML in the Taiwan Cancer Registry Database from 2011 to 2015. We excluded patients younger than 20 years, with acute promyelocytic leukemia, and with no pathological confirmation. RESULTS: Among the 3292 patients included, 2179 received induction chemotherapy and 1113 did not, because of older age and higher Charlson comorbidity index (CCI) score. Among the 2179 treated patients, 162 received high-dose cytarabine-based chemotherapy, 1535 received standard-dose cytarabine with anthracyclines, 209 received low-dose cytarabine-based chemotherapy, and 273 received chemotherapy without cytarabine. Patients in the low-dose cytarabine group had the oldest age and highest CCI scores compared with the other groups. In the analysis of overall survival (OS), the median OS of the overall study population was 6.27 months. Treated patients with AML had a longer OS than untreated ones (12.43 months treated vs. 2.03 months not treated; P < .0001). In the multivariate analyses of the treated patients with AML, several factors indicated better prognosis, including receiving standard-dose or high-dose cytarabine, female sex, younger age, lower CCI score, treatment at a medical center, favorable cytogenetic abnormalities, and allogeneic hematopoietic stem cell transplantation. CONCLUSION: Our study was a population-based study that illustrates the real-world outcomes of adult patients with AML in Taiwan.
Asunto(s)
Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/uso terapéutico , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Quimioterapia de Inducción , Leucemia Mieloide Aguda/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Sistema de Registros/estadística & datos numéricos , Estudios Retrospectivos , Análisis de Supervivencia , Taiwán/epidemiología , Resultado del TratamientoRESUMEN
OPINION STATEMENT: The treatment of acute myeloid leukemia (AML) has evolved considerably over the past several years. Advances in the field have historically benefited younger patients; however, a growing understanding of the molecular basis of leukemogenesis has brought multiple targeted agents to the clinic for patients of all ages. These therapies have expanded the therapeutic landscape for elderly patients from more than best supportive care and low-intensity monotherapy. In general, we currently utilize a backbone regimen of a hypomethylating agent (HMA) or low-intensity chemotherapy with the BCL-2 inhibitor venetoclax for the majority of elderly patients with newly diagnosed AML. For patients with targetable mutations, we employ a doublet/triplet strategy of HMA + a targeted inhibitor +/- venetoclax, often in the context of a clinical trial. CPX-351 is reserved for patients with secondary or therapy-related AML. In this review, we will outline our approach to the treatment of elderly patients with AML, with particular emphasis on recently approved agents and emerging novel therapies.