RESUMO
Background: Aggressive mature T-cell lymphoma (TCL) is a disease that carries a poor prognosis. Methods: We analyzed the expression of 22 tumor cell functional proteins in 16 randomly selected patients with TCL. Immunohistochemistry was performed in paraffin-embedded tumor tissue sections to determine the protein expression statuses in tumor cells. Results: Glucose-regulated protein 94 (GRP94), a protein that serves as a pro-survival component under endoplasmic reticulum (ER) stress in the tumor microenvironment, was significantly associated with a shortened survival. Furthermore, significant differences were observed when GRP94 was combined with six other factors. The six factors were (1) programmed cell death-ligand 1 (PD-L1); (2) programmed cell death 1 (PD-1); (3) aldo-keto reductase family 1 member C3 (AKR1C3); (4) P53, a tumor suppressor; (5) glucose-regulated protein 78 (GRP78), an ER stress protein; and (6) thymidine phosphorylase (TP). Based on the combination of GRP94 and the six other factors expressed in the tumors, we propose a new prognostic classification system for TCL (TCL Urayasu classification). Group 1 (relatively good prognosis): GRP94-negative (n = 6; median OS, 88 months; p < 0.01); Group 2 (poor prognosis): GRP94-positive, plus expression of two of the six factors mentioned above (n = 5; median OS, 25 months; p > 0.05); and Group 3 (very poor prognosis): GRP94-positive, plus expression of at least three of the six factors mentioned above (n = 5; median OS, 10 months; p < 0.01). Conclusions: Thus, the TCL Urayasu prognostic classification may be a simple, useful, and innovative classification that also explains the mechanism of resistance to treatment for each functional protein. If validated in a larger number of patients, the TCL Urayasu classification will enable a targeted treatment using selected inhibitors acting on the abnormal protein found in each patient.
RESUMO
We conducted a retrospective analysis of GRP94 immunohistochemical (IHC) staining, an ER stress protein, on large B-cell lymphoma (LBCL) cells, intracellular p53, and 15 factors involved in the metabolism of the CHOP regimen: AKR1C3 (HO metabolism), CYP3A4 (CHOP metabolism), and HO efflux pumps (MDR1 and MRP1). The study subjects were 42 patients with LBCL at our hospital. The IHC staining used antibodies against the 17 factors. The odds ratios by logistic regression analysis used a dichotomous variable of CR and non-CR/relapse were statistically significant for MDR1, MRP1, and AKR1C3. The overall survival (OS) after R-CHOP was compared by the log-rank test. The four groups showed that Very good (5-year OS, 100%) consisted of four patients who showed negative IHC staining for both GRP94 and CYP3A4. Very poor (1-year OS, 0%) consisted of three patients who showed positive results in IHC for both GRP94 and CYP3A4. The remaining 35 patients comprised two subgroups: Good (5-year OS 60-80%): 15 patients who showed negative staining for both MDR1 and AKR1C3 and Poor (5-year OS, 10-20%): 20 patients who showed positive staining for either MDR, AKR1C3, MRP1, or p53. The Histological Prognostic Index (HPI) (the four groups: Very poor, Poor, Good, and Very good) is a breakthrough method for stratifying patients based on the factors involved in the development of treatment resistance.
RESUMO
We conducted this study with the objective of elucidating the mechanism of development of fibrosis in hematologic neoplasms and develop treatments for these patients. Among the suggested mechanisms of development of fibrosis is cases of hematologic neoplasms is the production of TGF-beta1 (transforming growth factor-beta-1) and TNF-alpha1 (tumor necrotizing factor-alpha-1) by the tumor cells, both of which are fibrosis-stimulating cytokines that act on fibroblasts to promote fibrosis. However, there are few reports based on human clinical pathology studies. We conducted an immunohistochemical study on paraffin-embedded formalin-fixed specimens obtained from 104 patients with various pathologic conditions (acute leukemia, malignant lymphoma, inflammation, cancer, etc.). The association of tissue fibrosis with positive immunohistochemistry for TGF- beta1 and/or TNF-alpha1, TGF-beta1 was found to be strongly associated with tissue fibrosis, and in cases with positive immunohistochemistry for TGF-beta1, the odds ratio for fibrosis was 12.8, which was significantly high. Combined positivity for TGF-beta1 and TNF-alpha1 was also associated with a significant odds ratio for fibrosis of 3.4, suggesting that TGF-beta1 expression is an important prerequisite. TGF-beta1 has been suggested as playing a relatively important role in tissue fibrosis. Future clinical application of these cytokines for both diagnosis and treatment is expected.
Assuntos
Neoplasias Hematológicas , Fator de Crescimento Transformador beta1 , Humanos , Fator de Crescimento Transformador beta/metabolismo , Citocinas , FibroseRESUMO
TAFRO syndrome is a rare systemic inflammatory disease characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. We encountered a case of calreticulin mutation-positive essential thrombocythemia (ET) with TAFRO syndrome-like features, followed by a rapid fatal course. The patient had been on anagrelide therapy for approximately three years for management of ET; however, she suddenly stopped going for follow-up and discontinued the medicine for a year. She presented with fever and hypotension, suggestive of septic shock, and was transferred to our hospital. The platelet count at the time of admission to another hospital was 50 × 104 / µL; however, it decreased to 25 × 104 / µL upon transfer to our hospital and further decreased to 5 × 104 / µL on the day of her death. In addition, the patient showed remarkable systemic edema and progression of organomegaly. Her condition suddenly worsened and led to her death on the 7th day of hospitalization. Postmortem, serum and pleural effusion interleukin (IL)-6 and vascular endothelial growth factor (VEGF) levels were significantly increased. Consequently, a diagnosis of TAFRO syndrome, since she met the diagnostic criteria for clinical findings and had high cytokine concentrations. Dysregulation of cytokine networks has also been reported in ET. Therefore, concurrent ET and TAFRO syndrome may have further triggered cytokine storms and contributed to the aggravation of the disease on development of TAFRO syndrome. To the best of our knowledge, this is the first report of complications seen in a patient with TAFRO syndrome due to ET.
Assuntos
Hiperplasia do Linfonodo Gigante , Trombocitemia Essencial , Feminino , Humanos , Trombocitemia Essencial/complicações , Trombocitemia Essencial/diagnóstico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Hiperplasia do Linfonodo Gigante/diagnóstico , Edema/complicações , Edema/diagnóstico , Edema/tratamento farmacológico , Febre/tratamento farmacológico , CitocinasRESUMO
BACKGROUND: Clinicians can appropriately terminate treatment or reduce treatment intensity by determining prognostic factors of end-of-life chemotherapy. In particular, it provides important information for patients with hematological malignancies who receive chemotherapy until near-the-end of life compared with patients with solid tumors. This study aimed to clarify whether existing prognostic tools are associated with the survival in patients with end-of-life hematological malignancies who received chemotherapy. METHODS: We retrospectively reviewed the records of 247 patients diagnosed with hematological malignancies and died at our university hospital hematology ward between May 2015 and May 2021. We performed multivariate analysis in 82 (33.2%) patients who received end-of-life chemotherapy using the Palliative Prognostic Index (PPI) and inflammation-based prognostic models, such as the Glasgow Prognostic Score (GPS), Prognostic Nutritional Index (PNI), and Controlling Nutrition Status (CONUT). RESULTS: On comparing 82 patients who received end-of-life chemotherapy with 165 patients who did not, the proportion of patients with PPI group A, GPS score = 0, and CONUT normal/mild was significantly higher among patients who received chemotherapy. In multivariate analysis, we identified PPI groups B (2.0 < PPI ≤ 4.0) and C (PPI > 4.0) [hazard ratio (HR) 2.1290, 95% CI 1.1830-3.828, P = .01166, respectively] and age ≥ 65 years (HR 2.0170, 95% CI 1.1280-3.607, P = .01805) were associated with overall survival. CONCLUSION: PPI use and age were independent associating factors for patients with hematological malignancies receiving end-of-life chemotherapy. PPI, a popular prognostic tool may be helpful for patients and hematologists to make decisions about end-of-life care.
Assuntos
Neoplasias Hematológicas , Estado Nutricional , Humanos , Idoso , Estudos Retrospectivos , Prognóstico , Neoplasias Hematológicas/tratamento farmacológico , MorteRESUMO
Many patients with primary vitreoretinal lymphoma (PVRL) exhibit central nervous system (CNS) involvement either at the diagnosis or during follow-up. The prognosis in the patients of PVRL with relapsed or refractory CNS remains extremely poor. We herein report a patient with refractory PVRL who had recurrence in the spinal cord despite receiving high-dose methotrexate-based chemotherapy and whole-brain radiotherapy. The patient surprisingly responded to tirabrutinib temporarily. We believe that this case suggests the utility of this new target therapy.
Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma , Neoplasias da Retina , Humanos , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/patologia , Neoplasias da Retina/terapia , Corpo Vítreo/patologia , Neoplasias do Sistema Nervoso Central/patologia , Medula Espinal/patologia , Linfoma/diagnósticoRESUMO
PURPOSE: Uncertainty of prognosis is one reason patients with hematologic malignancies receive aggressive therapy near end of life more often than those with advanced solid tumors. It is unknown whether end-of-life prognosis prediction models are useful for patients with hematologic malignancies, especially hospitalized patients receiving chemotherapy, because most prognostic models were developed for patients with solid tumors. The purpose of this study was to evaluate the prognostic accuracy of the Palliative Prognostic Index (PPI) for end-of-life patients with advanced hematologic malignancies. METHODS: We retrospectively reviewed the records of 143 patients who became resistant to standard chemotherapy and died of disease progression in our university hospital hematology ward between May 2015 and November 2019. Patients were classified according to PPI scores (groups: A, PPI ≤ 2.0; B, 2.0 < PPI ≤ 4.0; and C, PPI > 4.0) based on their clinical charts at admission. The median overall survival for each patient (95% confidence interval) was calculated using the Kaplan-Meier method. Log-rank tests were used to determine significant differences between survival curves. RESULTS: Median patient age was 76 years (range: 39-92 years), and 59% were men. Median overall survival times in the PPI groups A, B, and C were 58 days, 36 days, and 10 days, respectively. Statistically significant differences in survival time were observed between the groups (P < .01); prediction accuracy was similar to that for patients with different diagnoses. CONCLUSION: The usefulness of PPI was validated for near-end-of-life hospitalized patients with hematologic malignancies.
Assuntos
Neoplasias Hematológicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Morte , Neoplasias Hematológicas/tratamento farmacológico , Hospitais , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
In Japan, ibrutinib has been approved as both a front-line and later-line treatment for chronic leukemia/small lymphocytic lymphoma(CLL/SLL). However, little is known about the actual outcomes and adverse events(AEs)associated with the use of ibrutinib in Japanese patients. OBJECTIVE: The outcomes and AEs of patients treated with ibrutinib in a real-world setting were investigated. METHODS: A retrospective cohort study of all patients with CLL/SLL who were treated with ibrutinib at a single institution was conducted. RESULT: In total, 10 patients, including 5 treatment-naïve patients(50%), were enrolled. The median follow-up period was 9.8 months(range, 0.2-21.6 months), and the estimated overall response rate (ORR: complete remission plus partial remission)was 60%. The median overall survival and progression-free survival outcomes were not reached. During the follow-up period, 4 patients(40%)had at least one AE and 1 patient(10%)had at least one grade≥3 AE. Ibrutinib was discontinued in 4 patients(40%)because of AEs in 2 patients(20%), the progression of CLL in 1 patient(10%), and financial reasons in 1 patient(10%). Richter's transformation did not occur in any of the cases. CONCLUSION: The ORR was lower(60%)than that observed in clinical trials. The frequency and severity of AEs were both relatively low, although the discontinuation rate was high(40%). Patient education and medication adherence were considered important.
Assuntos
Leucemia Linfocítica Crônica de Células B , Adenina/análogos & derivados , Humanos , Japão , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Piperidinas , Pirazóis/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A 42âyearâold woman. At week 27 of pregnancy, she developed subcortical hemorrhage and underwent open cranial surgery for hematoma evacuation. The platelet(Plt)count was 297,000/µL. At week 34 of pregnancy, she developed subcortical hemorrhage again. The Plt count was 429,000/µL. At week 35 of pregnancy, the ventricular rupture and she underwent drainage and emergency cesarean section. The Plt count was 687,000/µL. Two days after delivery, hemorrhage was detected. The Plt count was 815,000/µL. Six days after delivery, she developed infarction. The Plt count was 915,000/µL. MRI revealed no evidence of aneurysm, arteriovenous malformations or tumor. Ten days after delivery, the Plt count was 1,173,000/µL. Bone marrow examination led to the diagnosis of essential thrombocythemia(ET). JAK2, CARL and MPL was negative. She was rated as"lowârisk"by IPSETâthrombosis, and as"ultralow"risk by revised IPSETâthrombosis. von Willebrand factor(VWF)activity was as high as 247%. The bleeding time and platelet aggregation activity were normal. There was no evidence of disseminated intravascular coagulation(DIC)or hypertensive disorders of pregnancy(HDP). She died of cerebral hemorrhage and infarction, 26 days after delivery.
Assuntos
Trombocitemia Essencial , Adulto , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/etiologia , Cesárea , Feminino , Humanos , Período Pós-Parto , Gravidez , Trombocitemia Essencial/complicaçõesRESUMO
OBJECTIVE: We investigate the current status of screening for essential thrombocythemia(ET)and polycythemia vera(PV), at our hospital. METHODS: According to the World Health Organization(WHO)diagnostic criteria. PATIENTS: All patients who visited Juntendo University Urayasu Hospital between May 1984(when the hospital opened)and January 2019. RESULT: More than 90% of patients with elevated platelet counts(PLT)(n=25,062)and more than 90% of patients with elevated hemoglobin( Hb)or hematocrit(Ht)levels(n=16,422)did not visit the department of hematology, suggesting that there could be a high percentage of patients with potentially latent ET and PV visiting the hospital. In addition, a large number of patients fulfilling the laboratory criteria for ET/PV visited various departments of the hospital other than the department of hematology. CONCLUSION: Because ET/PV manifests with diverse symptoms, including non-specific symptoms and symptoms pertaining to other organ systems. Based on the findings, we consider that it is essential to disseminate information about the WHO diagnostic criteria/clinical symptoms and possibility of latent ET/PV to all departments of the hospital, and to establish cooperation between the department of hematology and other departments.
Assuntos
Policitemia Vera , Trombocitemia Essencial , Humanos , Policitemia Vera/diagnóstico , Policitemia Vera/epidemiologia , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/epidemiologiaRESUMO
A 47-year-old male with macroglossia presented with dyspnea on effort and chest pain at rest. Cardiac MRI revealed diffuse global subendocardial late gadolinium enhancement below the left ventricular endocardium and a dark blood pool of intracardiac contrast medium. Tongue biopsy revealed amyloid deposition, which was limited in the myocardium. He was diagnosed with primary light chain amyloidosis. His condition was stage I according to the Mayo Clinic staging system. He underwent autologous peripheral blood stem cell transplantation. On Day 10, he developed chest pain and died suddenly on Day 11. Postmortem examination revealed amyloid deposition throughout the heart.
Assuntos
Amiloidose/diagnóstico por imagem , Coração/diagnóstico por imagem , Amiloidose/terapia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Transplante de Células-TroncoRESUMO
A 63-year-old woman was referred to our department in 2015 because of anemia and thrombocytosis. MPL W515/K was positive, JAK-2V617F and CALR exon 9 were negative. Bone marrow(BM)biopsy led to a diagnosis of primary myelofibrosis (PMF)in the prefibrotic/early stage(Grade 1). BMbiopsy performed in 2016 showed overt fibrotic stage(Grade 2). She was classified according to the Dynamic International Prognostic Scoring System(DIPSS)as intermediate(Int)-â ¡risk. Ruxolitinib 10 mg daily was initiated. Ruxolitinib was suspended for hepatic dysfunction after the dose was increased to 15 mg. Subsequently, ruxolitinib was resumed at 10 mg. BM biopsy performed in 2017 showed progression of myelofibrosis(MF)to Grade 3. BM biopsy performed in 2018 showed improved to Grade 0-1, however, BM was fatty. Currently in 2019, she continues to be on ruxolitinib. Results of immunohistochemical staining of BM biopsy specimens for cytokines and CD34 suggested the role of cytokines in the pathogenesis of the PMF. It was speculated that ruxolitinib blocked the production of cytokines to ameliorate the MF and restore the hematopoietic function of the BM. Although the pathogenesis of the fatty marrow remained unclear, the possibility of involvement of ruxolitinib cannot be denied.
Assuntos
Mielofibrose Primária , Medula Óssea , Feminino , Fibrose , Humanos , Pessoa de Meia-Idade , Nitrilas , Mielofibrose Primária/tratamento farmacológico , Pirazóis , PirimidinasRESUMO
A 53-year-old woman had been diagnosed with rheumatoid arthritis (RA) in X-6. She was started on methotrexate (MTX) in X-1. She developed a cough, and chest computed tomography showed abnormalities. In X, MTX was discontinued, but the cough persisted. A lung biopsy revealed a diagnosis of nodular sclerosis classic Hodgkin lymphoma (CHL-NS). She was considered to have "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" (OIIA-LPD), MTX-associated Hodgkin lymphoma (MTX-HL). She received six courses of brentuximab vedotin (BV) in addition to AVD (BV+AVD). A complete metabolic response was obtained, and the RA went into remission. This is the fourth reported case of BV+AVD for MTX-HL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Doença de Hodgkin/induzido quimicamente , Doença de Hodgkin/tratamento farmacológico , Metotrexato/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Antirreumáticos/uso terapêutico , Brentuximab Vedotin/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Imunoconjugados/uso terapêutico , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento , Vimblastina/uso terapêuticoAssuntos
Aminopterina/análogos & derivados , Antineoplásicos/uso terapêutico , Linfoma de Células T Periférico/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Nucleosídeos de Purina/uso terapêutico , Pirimidinonas/uso terapêutico , Idoso , Aminopterina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Linfoma de Células T Periférico/patologia , Recidiva Local de Neoplasia/patologia , Prednisona/uso terapêutico , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/patologia , Vincristina/uso terapêuticoRESUMO
Autologous peripheral blood stem cell transplantation(auto-PBSCT)combined with high-dose chemotherapy has been considered as the standard therapy for relapsed or induction therapy-refractory aggressive lymphomas sensitive to chemotherapy. While various regimens have been applied as the conditioning,none has yet been established as the standard. We have begun to employ high-dose ranimustine,cytarabine,etoposide and cyclophosphamide(MCVAC)regimen. The present study was undertaken to review the efficacy and safety of MCVAC. Regimen: We carried out a retrospective analysis of 20 patients diagnosed as diffuse large B-cell lymphoma. The median follow-up duration of 20 patients was 13.05 months(range, 0.57-49.5 months). The 4-year OS and PFS were 57.8% and 30.2%,respectively. Relapse was the most frequent cause of treatment failure(n=7). The major toxicities were anorexia/nausea(95%),diarrhea (75%),hypokalemia (70%). One patient died of hepatic veno-occlusive disease(VOD). The serious adverse events included hypokalemia,arrhythmia,cerebral hemorrhage,and heart failure(1 case[5%]each). There was 1 case of a late-onset adverse event: therapy-related myelo- dysplastic syndrome/acute myeloblastic leukemia(MDS/AML). MCVAC regimen was concluded as effective and well-toler- ated. However,we should carefully monitored for the possible development of VOD and MDS/AML. Further follow-up is needed to evaluate the long-term efficacy and safety.
Assuntos
Linfoma Difuso de Grandes Células B , Transplante de Células-Tronco de Sangue Periférico , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Etoposídeo , Humanos , Linfoma Difuso de Grandes Células B/terapia , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante AutólogoRESUMO
OBJECTIVE: The clinical features(CF), laboratory data, disease transformation pattern and drug metabolism in essential thrombocythemia(ET)differ between Japan and Western countries. The CF of ET in clinical practice(CP)are more diverse than in prospective clinical studies. We should conduct retrospective analyses in CP. The present study was aimed at evaluating the efficacy, safety and tolerability of anagrelide(ANA)monotherapy and combined ANA plus hydroxycarbamide(HC)in Japanese ET. PATIENTS AND METHODS: We have a total of 35 cases. Sixteen patients received ANA monotherapy, 10 received ANA plus HC, and 9 received ANA plus other drugs. RESULTS: Comparison among three groups revealed the absence of differences in response rate(platelet count C60×10 / / 4/mL, platelet count C40×104/mL)(43.8%, 6.3% vs. 50.0%, 10.0% vs. 44.4%, 11.1%), treatment continuation rate(81.3% vs. 40.0% vs. 55.6%), median daily dose of ANA(1.00 mg in all three groups)or median treatment period(days)(259 vs. 198.5 vs. 161.0), the treatment continuation rate tended to be lower in the combined ANA plus HC. The incidence of all adverse events(AEs)was higher in the ANA monotherapy(45.7%)than ANA plus HC(28.6%)or ANA plus other drugs(25.7%), the AEs were mild in all groups. CONCLUSION: The tolerability of ANA monotherapy, ANA plus HC, and ANA plus other drugs were good.
Assuntos
Hidroxiureia/uso terapêutico , Quinazolinas/efeitos adversos , Trombocitemia Essencial , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Japão , Estudos Retrospectivos , Trombocitemia Essencial/tratamento farmacológicoRESUMO
A 59-year-old female was diagnosed as pulmonary aspergillosis(IPA)while remission induction therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia. Liposomal amphotericin B improved the fungal serodiagnostic markers, however,the IPA worsened. She also developed an Aspergillus brain abscess,which, while being undetectable on CT,was detected as multiple nodular lesions by MRI. A definitive diagnosis was made by polymerase chain reaction(PCR)of brain biopsy specimens. Voriconazole(VRCZ)was effective,and cord blood transplantation was performed. She has received VRCZ for a long time. There are no relapse of either the IPA or the Aspergillus brain abscess.
Assuntos
Abscesso Encefálico , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Aspergilose Pulmonar Invasiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Antifúngicos , Feminino , Humanos , Aspergilose Pulmonar Invasiva/complicações , Pessoa de Meia-Idade , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , VoriconazolRESUMO
Three patients under hemodialysis (HD) with relapsed/refractory multiple myeloma (MM) were administered panobinostat/bortezomib/dexamethasone (FVD). Case 1: The patient was a 66-year-old male with BJP-κ. FVD was effective, but HD could not be discontinued. He developed Grade 3 adverse events (AEs), including nausea, dehydration, and fatigue, following the common terminology criteria for adverse events v4.0. FVD was discontinued after the third course, while HD was continued. Case 2: The patient was a 65-year-old female with IgG-λ + BJP-λ. Amyloidosis was complicated. The first course of FVD was effective, but HD could not be discontinued. She developed G2 AEs, including nausea and fatigue. The cardiac amyloidosis worsened, and she died of heart and renal failure. Case 3: The patient was a 79-year-old male with BJP-κ. FVD was effective, and the HD could be discontinued on day 12 of treatment. No AEs were noted. However, he declined continuation of the FVD and died of MM relapse and renal failure. We analyzed the pharmacokinetics of panobinostat. There were no correlations between dose level and blood level of panobinostat or between blood level, efficacy, and incidence of AEs. We additionally measured the rate of elimination of the drug by HD.