RESUMEN
Patients with refractory or relapsed (R/R) large B-cell lymphoma (LBCL) refractory to first-line chemotherapy or with early relapse have poor outcomes. While chimeric antigen receptor (CAR) T-cell therapy has impressive efficacy after two or more lines of chemotherapy, it's still uncertain if these outcomes remain consistent in the context of third-line CAR T-cell therapy. We conducted a retrospective study of 107 R/R LBCL patients. Patients with relapse 12 months or more after their first-line chemoimmunotherapy (late failure: n = 25) had significantly longer overall survival (OS) than patients with refractory disease or relapse within 12 months (early failure: n = 82) (median OS: not achieved vs. 18.4 months; P < 0.001). Among patients who proceeded to autologous hematopoietic stem-cell transplantation (auto-HSCT), those with late failure had significantly longer event-free survival (EFS) than those with early failure (median EFS: 26.9 vs. 3.1 months; P = 0.012). However, no significant difference in EFS was detected among patients who underwent CAR T-cell therapy (median EFS: not reached vs. 11.8; P = 0.091). Cox regression with restricted cubic spline demonstrated that timing of relapse had significant impact on EFS in patients with auto-HSCT but not in patients with CAR T-cell therapy. Of patients who were scheduled for CAR T-cell therapy, those with late failure were significantly more likely to receive CAR T-cell therapy than those with early failure (90% vs. 57%; P = 0.008). In conclusion, patients with early failure still experienced poor outcomes after the approval of third-line CAR T-cell therapy.
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Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/mortalidad , Adulto , Estudios Retrospectivos , Pronóstico , Trasplante de Células Madre Hematopoyéticas , Receptores Quiméricos de Antígenos , RecurrenciaRESUMEN
Disease recurrence remains the principal cause of treatment failure after allogeneic hematopoietic stem cell transplantation. Post-transplant maintenance therapy with azacitidine (AZA) is promising to prevent relapse but the outcomes are unsatisfactory in patients at high risk of recurrence. Herein, we evaluated the outcome in patients who received AZA and gemtuzumab ozogamicin (GO), anti-CD33 antibody-calicheamicin conjugate, as post-transplant maintenance therapy. Twenty-eight patients with high-risk hematologic malignancies harboring CD33-positive leukemic blasts received the maintenance therapy. AZA (30 mg/m2) was administered for 7 days, followed by GO (3 mg/m2) on day 8. The maximum number of cycles was 4. At transplant, 21 patients (75.0%) had active disease. Their 2-year overall survival, disease-free survival, relapse, and non-relapse mortality rates were 53.6%, 39.3%, 50.0%, and 10.7%, respectively. Of these patients, those with minimal residual disease at the start of maintenance therapy (n = 9) had a higher recurrence rate (66.7% vs. 42.1% at 2 years, P = 0.069) and shorter disease-free survival (11.1% vs. 52.6% at 2 years, P = 0.003). Post-transplant maintenance therapy with AZA and GO was generally tolerable but more than half of the patients eventually relapsed. Further improvements are needed to prevent relapse after transplantation in patients with high-risk hematologic malignancies.
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Azacitidina , Gemtuzumab , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Humanos , Gemtuzumab/uso terapéutico , Masculino , Persona de Mediana Edad , Femenino , Azacitidina/uso terapéutico , Adulto , Trasplante de Células Madre Hematopoyéticas/métodos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/mortalidad , Anciano , Aminoglicósidos/uso terapéutico , Aminoglicósidos/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéuticoRESUMEN
A 28-year-old man was diagnosed with acute myelomonocytic leukemia. He achieved complete remission (CR) after two cycles of induction therapy. However, after consolidation therapy, bone marrow aspiration performed to prepare for allogeneic hematopoietic stem cell transplantation revealed disease relapse. Companion diagnostics confirmed the presence of the FLT3-ITD mutation. The patient received gilteritinib monotherapy and achieved CR. Subsequently, he underwent unrelated allogeneic bone marrow transplantation. One year after transplantation, the patient relapsed, and gilteritinib was resumed. However, the leukemia progressed, and panel sequencing using a next-generation sequencer showed that the FLT3-ITD mutation disappeared. A mutation in PTPN11, which regulates the RAS/MAPK signaling pathway, was also detected. Gilteritinib was discontinued, and the patient achieved CR with salvage chemotherapy. He underwent related haploidentical peripheral blood stem cell transplantation but died of relapse. This was a case in which genetic analysis revealed clonal transition and acquisition of resistance to treatment.
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Leucemia Mieloide Aguda , Masculino , Humanos , Adulto , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Compuestos de Anilina , Pirazinas , Enfermedad Crónica , Mutación , Respuesta Patológica Completa , Tirosina Quinasa 3 Similar a fms/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genéticaRESUMEN
A 63-year-old man with adult T-cell leukemia-lymphoma underwent allogeneic bone marrow transplantation from an HLA-matched unrelated donor. On day 17 after transplantation, chest computed tomography (CT) showed nodules in the lower lobes of both lungs, and invasive pulmonary aspergillosis (IPA) was suspected. Treatment with liposomal amphotericin B was started, and improvement of infectious lesions was confirmed with CT on day 28. The antifungal agent was changed to voriconazole on day 52 because of progressive renal dysfunction. Disorders of consciousness and paralysis of the left upper and lower extremities developed on day 61. Brain CT showed subcortical hemorrhage in the right parietal and occipital lobes, and the patient died on day 62. An autopsy revealed filamentous fungi, suspected to be Aspergillus, in the pulmonary nodules and a ruptured cerebral aneurysm. Although IPA occurs in 10% of transplant recipients, vigilant monitoring for mycotic cerebral aneurysms is required to prevent hematogenous dissemination of Aspergillus, which is associated with a high mortality rate.
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Trasplante de Células Madre Hematopoyéticas , Aneurisma Intracraneal , Leucemia-Linfoma de Células T del Adulto , Linfoma , Adulto , Masculino , Humanos , Persona de Mediana Edad , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/terapia , Leucemia-Linfoma de Células T del Adulto/complicaciones , Leucemia-Linfoma de Células T del Adulto/terapia , Trasplante de Médula ÓseaRESUMEN
An 18-year-old man underwent allogenic bone marrow transplantation (BMT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Ph+ALL relapsed 3 months after the first BMT, and the patient underwent a second BMT. However, Ph+ALL relapsed 4 months after the second BMT, and he received a haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) from his father. Molecular complete remission was confirmed 29 days after haplo-PBSCT. However, the patient needed dialysis for end-stage renal disease due to thrombotic microangiopathy 3 years and 2 months after haplo-PBSCT. He received a kidney transplantation from his father 7 years and 10 months after haplo-PBSCT, and got off dialysis after the kidney transplantation. Immunosuppressive therapy with methylprednisolone, tacrolimus, and mycophenolate mofetil was started for kidney transplantation, but the dose of immunosuppressive agents was reduced successfully without rejection soon after kidney transplantation. The patient has maintained long-term remission since the haplo-PBSCT, and his kidney function was restored by the kidney transplantation from his father.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Fallo Renal Crónico , Trasplante de Riñón , Leucemia-Linfoma Linfoblástico de Células Precursoras , Masculino , Humanos , Adolescente , Cromosoma Filadelfia , Trasplante Homólogo , Trasplante de Médula Ósea , Enfermedad Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMEN
OBJECTIVE: The prognosis of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. Although patients who fail first-line salvage chemotherapy are candidates for second-line salvage chemotherapy, the optimal treatment strategy for these patients has not yet been established. METHODS: The present, single-center, retrospective study included transplant-eligible patients with R/R DLBCL who received second-line salvage chemotherapy with curative intent. RESULTS: Seventy-six patients with R/R DLBCL received second-line salvage chemotherapy. Eighteen (23.7%) patients were responders to the first-line salvage chemotherapy. The overall response rate was 39.5%, and overall survival (OS) was significantly longer in patients who responded to second-line salvage chemotherapy than those who did not. Forty-one patients who proceeded to potentially curative treatment (autologous hematopoietic stem cell transplantation [ASCT], chimeric antigen receptor [CAR] T-cell therapy, or allogeneic hematopoietic stem cell transplantation) had a better prognosis than those who did not. Among the 46 patients who failed to respond to the second-line salvage regimen, only 18 (39.1%) could proceed to the curative treatments. However, among the 30 patients who responded to the second-line salvage regimen, 23 (76.7%) received one of the potentially curative treatments. Among 34 patients who received CAR T-cell therapy, OS was significantly longer in those who responded to salvage chemotherapy immediately prior to CAR T-cell therapy than in those who did not respond. In contrast, the number of prior lines of chemotherapy was not identified as a statistically significant prognostic factor of survival. No significant difference was detected in OS between patients receiving ASCT and those receiving CAR T-cell therapy after the response to second-line salvage chemotherapy. DISCUSSION: In this study, we demonstrated that chemosensitivity remained a crucial factor in predicting survival outcomes following CAR T-cell therapy irrespective of the administration timing, and that both ASCT and CAR T-cell therapy were acceptable after the response to second-line salvage chemotherapy.
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Pola-BR (polatuzumab vedotin, bendamustine, and rituximab) therapy received approval for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in Japan in March 2021. There have been few reports on the efficacy and safety of Pola-BR therapy in Japanese clinical practice. A retrospective analysis was performed on twenty-nine patients with R/R DLBCL who received Pola-BR therapy at our institution (intent to cellular immunotherapy cohort: 20 patients, stand-alone treatment cohort: nine patients). The overall response rate was 69.0% (complete response 27.6%). The median progression-free survival was 5.1 months, with a 9.5-month median overall survival. In the intent to cellular immunotherapy cohort, 11 of 19 patients received chimeric antigen receptor T-cell (CAR-T) infusions, and one patient received allogeneic stem cell transplantation. Four patients received Pola-BR therapy, including bendamustine before leukapheresis, and all produced CAR-T products successfully. 3 of the 28 patients experienced grade3 or higher adverse events, and two required treatment discontinuation. Our single institution, a real-world cohort of R/R DLBCL patients showed high efficacy outcomes and a tolerable toxicity profile for Pola-BR therapy, which is comparable to previous studies. More cases are needed to determine its impact on CAR-T therapy and stem cell transplantation.
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Trasplante de Células Madre Hematopoyéticas , Inmunoconjugados , Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Receptores Quiméricos de Antígenos , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Clorhidrato de Bendamustina/uso terapéutico , Tratamiento Basado en Trasplante de Células y Tejidos , Inmunoconjugados/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Receptores Quiméricos de Antígenos/uso terapéutico , Estudios Retrospectivos , Rituximab/uso terapéuticoRESUMEN
Young adults with myelodysplastic syndrome (MDS) are rare, and the clinical significance of driver mutations has not yet been analysed. We analysed the gene mutations and copy number alterations (CNAs) in younger MDS patients using next-generation sequencing, targeting 68 genes that were recurrently mutated in myeloid malignancies, to investigate the correlation between their genetic alterations and clinical outcomes. We enrolled 55 patients retrospectively (aged < 50 years). At least one mutation was detected in 56% of the patients. The most frequently mutated genes were ASXL1 and RUNX1, 13% each. We defined higher-risk patients as those with ≥ 2 mutations, except for SF3B1 mutation, and/or CNA. The 3-year overall survival (OS) in patients with a higher-risk was lower than that in those with a lower-risk (50.8% vs. 71.8%, P = 0.024). Among the 44 transplant recipients, patients with higher-risk had a significantly lower OS and tended to have a higher cumulative incidence of relapse (CIR) than those with a lower-risk (3-year OS: 38.0% vs. 64.4%, P = 0.039; 3-year CIR: 44.0% vs. 24.1%, P = 0.076). Our results showed that genetic aberrations can predict clinical outcomes in younger MDS patients, despite the low rate of genetic mutations.
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Adulto Joven , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Mutación , Leucemia Mieloide Aguda/genética , Factores de Transcripción/genética , PronósticoRESUMEN
Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disease characterized by intravascular hemolysis, thrombosis, and bone marrow (BM) failure. Although PNH is caused by excessive proliferation of hematopoietic stem cell (HSC) clones with loss of function mutations in phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) genes, what drives PNH clones to expand remains elusive. Case description: We present a case of a 26-year-old female who presented with hemolytic anemia, thrombocytopenia, and leukopenia. Flow cytometry analysis of peripheral blood showed that 71.9% and 15.3% of the granulocytes and erythrocytes were glycosylphosphatidylinositol-anchored protein deficient (GPI[-]) cells. The patient was diagnosed with PNH with non-severe aplastic anemia. Deep-targeted sequencing covering 390 different genes of sorted GPI(-) granulocytes revealed three different PIGA mutations (p.I69fs, variant allele frequency (VAF) 24.2%; p.T192P, VAF 5.8%; p.V300fs, VAF 5.1%) and no other mutations. She received six cycles of eculizumab and oral cyclosporine. Although the patient's serum lactate dehydrogenase level decreased, she remained dependent on red blood cell transfusion. Six months after diagnosis, she received a syngeneic bone marrow transplant (BMT) from a genetically identical healthy twin, following an immune ablative conditioning regimen consisting of cyclophosphamide 200 mg/kg and rabbit anti-thymocyte globulin 10 mg/kg. After four years, the patient's blood count remained normal without any signs of hemolysis. However, the peripheral blood still contained 0.2% GPI (-) granulocytes, and the three PIGA mutations that had been detected before BMT persisted at similar proportions to those before transplantation (p.I69fs, VAF 36.1%; p.T192P, VAF 3.7%; p.V300fs, VAF 8.6%) in the small PNH clones that persisted after transplantation. Conclusions: The PNH clones that had increased excessively before BMT decreased, but persisted at low percentages for more than four years after the immunoablative conditioning regimen followed by syngeneic BMT. These findings indicate that as opposed to conventional theory, immune pressure on HSCs, which caused BM failure before BMT, was sufficient for PIGA-mutated HSCs to clonally expand to develop PNH.
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Anemia Aplásica , Hemoglobinuria Paroxística , Femenino , Humanos , Adulto , Hemoglobinuria Paroxística/diagnóstico , Glicosilfosfatidilinositoles/genética , Células Madre Hematopoyéticas/metabolismo , Anemia Aplásica/genética , Anemia Aplásica/complicaciones , Células Clonales/metabolismoRESUMEN
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the approach to patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study retrospectively analyzed patients treated with commercially available tisagenlecleucel at our hospital and evaluated its safety and effectiveness. Of the 21 patients evaluated, any grade and grade ≥3 cytokine release syndrome (CRS) occurred in 85.7% and 9.5% of the patients, respectively. A total of 66.7% received tocilizumab and 28.6% received glucocorticoids for the treatment of CRS. The complete response (CR) rate at 3 months was 61.9% (95% confidence interval [CI] 38.4-81.9). After a median follow-up of 6.3 months following CAR-T infusion, the progression-free survival (PFS) and overall survival rates at 6 months were 53.1% (95%CI 28.3-72.7) and 69.2% (95%CI 43.7-84.9), respectively. Severe cytopenia and hypogammaglobulinemia occurred frequently following CAR-T infusion. Eight patients (38.1%) had comorbidities that would have made them ineligible for leukapheresis in the JULIET trial. However, the presence of comorbidities at the time of leukapheresis had no significant effect on the rates of CR, PFS, and adverse events. Tisagenlecleucel for r/r DLBCL in the real-world setting showed high efficacy and manageable safety profile comparable with the pivotal trial.
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Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/uso terapéutico , Estudios Retrospectivos , Receptores de Antígenos de Linfocitos T , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Inmunoterapia Adoptiva/efectos adversos , Antígenos CD19RESUMEN
RATIONALE: Chimeric antigen receptor (CAR) T-cell therapy is effective in treating relapsed and refractory B-cell non-Hodgkin lymphoma. However, because of the mortality risk associated with immune effector cell-associated neurotoxicity syndrome and pseudoprogression, patients with central nervous system (CNS) involvement are less likely to receive CAR T-cell therapy. PATIENTS CONCERNS: We report a case of a 61-year-old, male patient with intravascular large B-cell lymphoma who suffered a CNS relapse after standard chemotherapy. DIAGNOSIS: A diagnosis of intravascular large B-cell lymphoma with CNS involvement was made. INTERVENTIONS: We treated the patient using CAR T-cell therapy following a conditioning regimen consisting of thiotepa and busulfan and autologous stem cell transplantation. Although he experienced grade 1 cytokine release syndrome, no other serious adverse events, such as immune effector cell-associated neurotoxicity syndrome or pseudoprogression, were observed. OUTCOMES: The patient achieved complete remission after the CAR T-cell infusion. LESSONS: CAR T-cell therapy following autologous stem cell transplantation is a viable option for relapsed/refractory lymphoma with CNS infiltration. Further clinical studies are warranted to verify its safety and efficacy.
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Neoplasias del Sistema Nervioso Central/terapia , Trasplante de Células Madre Hematopoyéticas , Inmunoterapia Adoptiva/métodos , Linfoma de Células B Grandes Difuso/terapia , Neoplasias Primarias Secundarias/terapia , Síndromes de Neurotoxicidad , Receptores Quiméricos de Antígenos , Trasplante Autólogo/efectos adversos , Sistema Nervioso Central , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Receptores de Antígenos de Linfocitos TAsunto(s)
Trasplante de Células Madre Hematopoyéticas , Mutación , Aberraciones Cromosómicas Sexuales , Cromosomas Sexuales/genética , Donantes de Tejidos , Adulto , Anciano , Aloinjertos , ADN Metiltransferasa 3A/genética , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/efectos adversos , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Hibridación Fluorescente in Situ , Masculino , Proteína de la Leucemia Mieloide-Linfoide/genética , Pancitopenia/etiología , Polimorfismo de Nucleótido Simple , Estudios Retrospectivos , Trombocitopenia/etiología , Quimera por Trasplante/genética , Proteína p53 Supresora de Tumor/genética , Adulto JovenRESUMEN
A 58-year-old male was diagnosed with splenic B-cell lymphoma/leukemia, unclassifiable (SPLL-U). The lymphoma transformed into diffuse large B-cell lymphoma (DLBCL), and multidrug chemotherapy and autologous stem cell transplantation achieved complete remission. Two years later, the lymphoma relapsed as SPLL-U. Serial whole-exome sequencing indicated that the mutation profiles were similar between the onset and relapsed samples while those in DLBCL were partially distinctive, which was in line with the clinical course. Hierarchical clustering revealed that an IGLL5 mutation was the founder mutation proceeding the development of the diseases and suggested that KRAS and other mutations might contribute to the transformation.
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Outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in nonremission acute myeloid leukemia (AML) are dismal [2-year overall survival (OS): 20-30%]. Though several risk classifications have been used, some factors are unavailable until the start of conditioning or transplantation. We analyzed prognostic gene mutations by targeted next-generation sequencing to identify predisposing factors for predicting OS at 1 month before transplantation. We enrolled 120 patients with nonremission AML who underwent first allo-HSCT between 2005 and 2018. Mutations were found in 98 patients; frequently mutated genes were FLT3-ITD, TP53, RUNX1, and WT1. TP53 mutation was detected in 21 patients and was the only predictor of poor OS. Multivariate analysis using Cox regression hazard model revealed primary AML, monosomal karyotype (MK), and TP53 mutation as independent factors for predicting poor OS. Based on these, patients were stratified into three groups. The low-risk group included patients with prior myeloid disorder without MK (n = 26). Among the rest, patients with TP53 mutation were assigned to the high-risk group (n = 19) and the rest into the intermediate-risk group (n = 75). Two-year OS in low-, intermediate-, and high-risk groups differed significantly (50.0%, 24.9%, and 0%, respectively). This suggests that the indication of allo-HSCT should be carefully judged for high-risk patients.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Cariotipo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutación , Pronóstico , Proteína p53 Supresora de Tumor/genéticaRESUMEN
A 51-year-old man underwent allogeneic bone marrow transplantation (BMT) for recurrent acute myeloid leukemia. Although the patient developed slight edema, pleural effusion, and cardiac effusion 6 months after BMT, his clinical condition improved with furosemide treatment. The patient was transfused with red blood cells for the management of anemia 8 months after BMT. He developed acute respiratory failure with pulmonary alveolar hemorrhage 80 min after the transfusion. He was diagnosed with transfusion-associated circulatory overload (TACO) due to the presence of acute pulmonary congestion and depressed left ventricular systolic function. Reduced circulatory load due to sufficient furosemide led to ventilator weaning 3 days later. Other causes of pulmonary alveolar hemorrhage were excluded, and the patient's condition improved by cardiac failure treatment only. This clinical course indicated that pulmonary alveolar hemorrhage would breakdown the blood vessels due to acute pulmonary congestion. Chemotherapy and prolonged anemia are high risks for cardiac failure in patients with hematological malignancies. Therefore, the possibility of cardiac failure is considered when patients with hematological malignancies have fluid retention, such as cardiac enlargement, edema, and pleural effusion. Moreover, the body fluids should be monitored before and after blood transfusion.
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Trasplante de Médula Ósea/efectos adversos , Hemorragia/etiología , Edema Pulmonar/etiología , Reacción a la Transfusión , Transfusión Sanguínea , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Although peripheral blood stem cell (PBSC) transplantations in an unrelated transplant setting have been performed since 2010, prior harvesting and cryopreservation of PBSCs from unrelated donors has not been approved in Japan. There are no restrictions with regard to related donors. Therefore, in April 2015, we conducted a nationwide survey and obtained written answers from 123 transplant hospitals throughout Japan. Our survey revealed that as much as 81.3% of transplant hospitals routinely perform prior harvesting and cryopreservation of PBSCs from related donors and that both cell processing and quality management of cryopreserved products have been appropriately conducted in line with domestic guidelines, although post-thaw quality control and storage period setting require further improvements. Moreover, informed consent obtained from both patients and donors with regard to cryopreservation of PBSCs was not always sufficient in some hospitals. We found that the average number of unused or discarded cryopreserved PBSCs is 1.09 per hospital, and the overall nonuse or discard rates of cryopreserved PBSCs were estimated to be as low as 2.67%.
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Criopreservación , Células Madre de Sangre Periférica , Donantes de Sangre , Humanos , Japón , Encuestas y CuestionariosRESUMEN
BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) is widely used to mobilize peripheral blood stem cells (PBSCs) in healthy donors. A few reports have shown that some healthy donors developed acute respiratory distress syndrome or capillary leak syndrome after more than several rounds of G-CSF administration or leukapheresis. CASE REPORT: We report the case of a healthy donor for allogeneic stem cell transplantation who developed severe hypoxemia 1 h after only the first administration of G-CSF. The donor was administered 10 µg/kg G-CSF (lenograstim) subcutaneously for PBSC mobilization. 1 h after the first administration of G-CSF, the donor suddenly presented with dry cough and dyspnea. The oxygen saturation by pulse oximetry (SpO2) in the room air was 88%. An electrocardiogram and chest radiography revealed no abnormalities. We excluded other causes of severe hypoxemia and diagnosed the donor with hypoxemia due to G-CSF administration, which was subsequently terminated. The donor was administered 2 l/min oxygen via a nasal cannula and 100 mg hydrocortisone intravenously. He subsequently recovered, and SpO2 in the room air returned to 98% 10 h after hypoxemia. CONCLUSION: These respiratory symptoms might be related to anaphylactoid or hypersensitivity reaction. The donors should be observed for at least 1 h after the first administration of G-CSF.
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Recent studies have shown that CD25 expression at the time of diagnosis of acute myeloid leukemia (AML) may be associated with an unfavorable outcome. We focus on patients with AML without complete remission (CR) and examine the clinical correlation between surface CD25 expression at the time of transplant and subsequent transplant outcomes. We observed a significant difference in overall survival (OS), disease-free survival (DFS) and cumulative incidence of relapse (CIR) between CD25 positive (+) (n = 22) and negative (-) groups (n = 44) (2-year OS; CD25 (+) group: 5% vs. CD25 (-) group: 40%, p < 0.0001, 2-year DFS; 5% vs. 29%, p < 0.0001, 2-year CIR; 77% vs. 52%, p = 0.03). Multivariate analysis showed that CD25 expression was an independent adverse factor for OS (p = 0.002) and relapse (p = 0.001). Patients with AML with residual CD25 positive blasts at the time of transplant may require additional therapy before or after transplant to improve survival.
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Biomarcadores de Tumor , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/metabolismo , Neoplasia Residual/diagnóstico , Neoplasia Residual/metabolismo , Adulto , Anciano , Causas de Muerte , Femenino , Citometría de Flujo , Expresión Génica , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunofenotipificación , Subunidad alfa del Receptor de Interleucina-2/genética , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Acondicionamiento Pretrasplante , Trasplante HomólogoRESUMEN
Increased levels of normal B cell precursors, termed hematogones (HGs), are observed in regenerating bone marrow after chemotherapy or hematopoietic stem cell transplantation (HSCT). Recent reports suggest that emergence of HGs is associated with better outcomes following allogeneic HSCT (allo-HSCT). We reviewed the emergence of HGs and the clinical features of 192 patients after allo-BMT. Patients undergoing allo-BMT from related donors were more likely to develop HGs at day 30 compared to unrelated donors. Furthermore, patients undergoing allo-BMT from HLA-mismatched donors were less likely to develop HGs at day 30. The emergence of HGs at day 30 was an independent prognostic factor among patients who underwent BMT. We found no difference in the relapse rate between HG-positive (+) and HG-negative (-) patients undergoing BMT. HG (-) patients had high non-relapse mortality, grade II to IV acute graft-versus-host-disease (GVHD), fungal infection, and lower IgG levels compared to HG (+) patients. The emergence of HGs at day 30 among patients undergoing BMT may be a very useful indicator of subsequent survival outcomes or acute GVHD in common clinical practice.