RESUMO
A 56-year-old female presented with popliteal venous thrombosis, splenomegaly, and sclerotic bone lesions. Bone marrow biopsy showed fibrosis, proliferation of abnormal blood vessels and lymphatics, bone remodelling, and no significant changes in haematopoietic elements. Following a relatively indolent initial clinical course, one year later she rapidly deteriorated and died of respiratory failure associated with widespread disease. Ingrowth of podoplanin+ lymphatics mixed with CD34+/podoplanin- blood vessels into the bone marrow is a new finding and may be a unique feature of this disease.
Assuntos
Angiomatose/patologia , Doenças Ósseas/patologia , Vasos Linfáticos/patologia , Biópsia , Medula Óssea/patologia , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-IdadeAssuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Evolução Clonal/genética , Humanos , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Translocação GenéticaRESUMO
OBJECTIVE: In this retrospective single-centre study, we have looked into the transplant outcomes(overall survival OS, progression-free survival PFS, GvHD) and the role of chimerism, DLI and pretransplant characteristics in patients who had a suboptimal response (<12 months) to an autologous stem cell transplant for myeloma and underwent an alemtuzumab T-cell depleted reduced-intensity allograft(RIC). METHODS: Twenty-four patients were salvaged with two cycles of DT-PACE and received a RIC transplant with fludarabine, melphalan and alemtuzumab. All the patients received PBSC grafts, eight patients had a sibling donor, and 16 had a graft from a fully matched unrelated donor. The median follow-up was 65.3 months (6-132 months). RESULTS: The median overall survival was 55.4 months. DLI administration was associated with a trend towards better overall survival (P=.05). Disease status at allo-HCT, PR or VGPR, ISS score and CMV serostatus was not significant predictors of OS and PFS. Full donor whole blood chimerism (≥98%) at 3 months post-transplant was associated with PFS (P=.04) but did not have a significant impact on OS(P=.45). CONCLUSION: Reduced-intensity alemtuzumab-conditioned allograft for myeloma after DT-PACE salvage chemotherapy is an efficient and low toxicity treatment for those who had a suboptimal response postautologous stem cell transplant for myeloma.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Terapia Combinada , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Seguimentos , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Estadiamento de Neoplasias , Recidiva , Retratamento , Análise de Sobrevida , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Quimeras de Transplante , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoAssuntos
Transplante de Medula Óssea , Infecções por Coronavirus/complicações , Transplante de Células-Tronco Hematopoéticas , Pneumonia Viral/complicações , Transplantados , Adulto , Idoso , Betacoronavirus , COVID-19 , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2RESUMO
The present study describes a patient aged 70 with very high-risk AML who successfully received a nonmyeloablative matched unrelated donor allograft shortly following SARS-CoV-2 infection, which manifested with mild cough, interstitial abnormalities on chest CT, and pancytopenia with profound bone marrow biopsy histological alterations. In parallel, our study provides bone marrow biopsy data in a series of contemporary patients with serious haematological diseases who had a bone marrow biopsy performed within two weeks of PCR confirmation of SARS-CoV-2 infection. This study is notable because there are no published data describing the bone marrow biopsy changes observed in patients with haematological malignancies and SARS-CoV-2 infection. Finally, it is suggested that nonmyeloablative hematopoietic stem cell transplantation for very high-risk haematological malignancies can be successfully performed following recovery from SARS-CoV-2 infection.
RESUMO
Bone marrow transplantation is frequently used as a consolidation therapy in patients with haematological malignancies to improve the outcome of these patients. Obese individuals have larger absolute lean body and fat masses than non-obese individuals of the same age, gender and height, which might lead to altered pharmacokinetics of chemotherapeutic agents. Data on the impact of body mass on transplant outcome is conflicting. This study included 331 patients (M, 230; F, 101) with 336 allogeneic transplant episodes from two large teaching hospitals in the West Midlands region in United Kingdom. A total of 105 patients had acute myeloid leukaemia, 83 had non-Hodgkin's lymphoma, three had myeloma, 21 had Hodgkin's lymphoma, 34 had acute lymphoblastic leukaemia, 19 had chronic myeloid leukaemia, 22 had chronic lymphocytic leukaemia, 24 had myelodysplasia, seven had T cell non-Hodgkin's lymphoma, six had aplastic leukaemia and seven had myelofibrosis. At transplantation, 40% (N = 133) of the patients had normal and 60% (N = 198) had high body mass index (BMI) with 14% of the patients being obese (BMI >30). After a median follow-up of 24 months (range, 2-79), the mean overall survival (OS) in patients undergoing allograft with normal BMI was 31 months as compared to 39 with high BMI (p:0.06). The mean progression free survival (PFS) in patients undergoing allograft with normal BMI was 33 months as compared to 38 with high BMI (p = 0.13). Of the patients in the high and obese BMI group, 16% developed acute GvHD with 8% grade III-IV and 28% in the normal BMI group with 14% grade III-IV acute GvHD (p = 0.11). Of the patients in the high BMI group, 17% developed chronic GvHD and 30% of the patients in the normal BMI group (p = 0.09). However, higher infection rates and more days of inpatient stay in the first year post-transplant were observed in the high BMI and obese patients, but there was no difference in ITU admissions. This study shows that high BMI and obesity does not adversely impact on either OS or PFS in patients undergoing allogeneic transplantation for haematological malignancies, but it does have a significant impact on infection rates and hospitalisation of high BMI and obese patients. We recommend that patients with high BMI should not be excluded from allogeneic transplantation; however, good supportive care and careful patient selection on the basis of comorbidity index should be undertaken in order to avoid the risks from the increased rates of infection.
Assuntos
Índice de Massa Corporal , Transplante de Medula Óssea , Neoplasias Hematológicas/terapia , Transplante Homólogo , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Stem cell transplantation remains the curative option for many patients with hematological malignancies. The long-term effects of these treatments on the patients and their immune systems have been extensively investigated, but there remains a paucity of data regarding autoimmune manifestations post-transplant, although these effects are well recognized.Herein we present the clinical picture and therapeutic approach in three patients (cases 1-3), with varied presentations of autoimmune disease post-transplant. Case 1 exhibited autoimmune hemolytic anemia and other autoimmune manifestations (serositis, thyroiditis), that were probably linked to graft versus relapsed leukemia effect. Cases 2 and 3 had pure red white cell aplasia and pure red cell aplasia, respectively, which were associated with hyperglobulinemia and a clonal T cell expansion.
Assuntos
Alemtuzumab/efeitos adversos , Doenças Autoimunes/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante HomólogoRESUMO
Herein we present a female patient aged 61 with Philadelphia negative acute lymphoblastic leukaemia demonstrating near haploid karyotype and abnormal TP53 expression at diagnosis, who relapsed with lineage switch as Acute Monocytic Leukemia post allogeneic stem cell transplantation. Molecular analysis established that both neoplasms were derived from the same founder clone. The leukemic lineage switch phenomenon has recently re-attracted interest as mechanism of leukemic evasion post treatment with chimeric antigen receptor T-cells but there is paucity of data on its presence post allograft or following novel antibody treatments such as Inotuzumab Ozogamicin or Blinatumomab. Our proposition for cancer research is that near haploidy in ALL could be linked to leukemic stem cell plasticity evading stem cell transplantation and other immunotherapy approaches.
RESUMO
A unique case of primary refractory FLT3-itd mutated acute myeloid leukemia in an elderly patient, who achieved completed morphological remission, and FLT3-itd negativity, following 9 cycles of azacitadine in combination with escalating doses of donor lymphocyte infusions following relapse 18 months post reduced intensity HLAA mismatch Campath conditioning allogeneic stem cell transplant.
RESUMO
Reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation is increasingly considered for patients with chronic lymphocytic leukemia (CLL). To investigate the impact of in vivo T cell depletion with alemtuzumab on the incidence of graft-versus-host disease (GVHD), nonrelapse mortality (NRM), progression-free survival (PFS), and overall survival (OS), we retrospectively analyzed the outcomes of 62 consecutive CLL patients conditioned with fludarabine and melphalan at 4 institutions. For GVHD prophylaxis, 41 patients (cohort 1) received alemtuzumab and cyclosporin; and 21 patients (cohort 2) received cyclosporin plus methotrexate or mycophenolate. Donors were 50 siblings and 12 unrelated volunteers. Twenty-two (36%) patients received donor lymphocyte infusions (DLI), 20 (49%) from cohort 1 and 2 (10%) from cohort 2 (P=.002). Grade III-IV acute GVHD (aGVHD) was observed in 20% and 38% of patients from cohorts 1 and 2, respectively (P=.14). Extensive chronic GVHD (cGVHD) was observed in 10% and 48% of patients from cohorts 1 and 2, respectively (P=.03). There was a trend toward a higher viral infection rate in cohort 1 compared to cohort 2 (68% versus 43%, P=.062), but the incidence of cytomegalovirus (CMV) reactivation was not significantly different. The 3-year OS, PFS, NRM, and relapse rates were 65%, 39%, 28%, and 32%, respectively, for cohort 1; and 57%, 47%, 34%, and 20%, respectively, for cohort 2 (P=.629, P=.361, P=.735, and P=0.112, respectively). In conclusion, both methods of GVHD prophylaxis were equivalent in terms of survival. The administration of alemtuzumab led to reduced cGVHD, possibly improving quality of life.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Crônica de Células B/terapia , Depleção Linfocítica , Condicionamento Pré-Transplante , Adulto , Alemtuzumab , Anticorpos Monoclonais Humanizados , Estudos de Coortes , Ciclosporina/administração & dosagem , Citomegalovirus , Infecções por Citomegalovirus , Intervalo Livre de Doença , Seleção do Doador , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Imunossupressores/administração & dosagem , Leucemia Linfocítica Crônica de Células B/mortalidade , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida , Linfócitos T , Transplante Homólogo , Ativação Viral/efeitos dos fármacosRESUMO
BACKGROUND: Epidemiological findings of higher injury incidence during the latter stages of soccer match-play have been attributed to fatigue. OBJECTIVE: To examine the interaction of physical and cognitive responses during soccer-specific intermittent exercise. METHOD: Ten semi-professional soccer players completed a 90-minute laboratory-based treadmill protocol replicating the activity profile of soccer match-play. Two separate trials were performed in randomised order, with and without the added stressor of a continuous grid-based vigilance task. The exercise task comprised six repetitions of a 15 minute activity profile, separated by a passive 15 minute half-time interval. The vigilance task required continual attention and sporadic target response within a letter grid. Physical response (RPE, heart rate, blood lactate, salivary cortisol) and cognitive performance (response time, response accuracy) were quantified at 15 minute intervals. RESULTS: Completing the exercise task with the vigilance task resulted in decreased physiological (heart rate, blood lactate) response. This may be attributed to externally directed attention, resulting in association with the cognitive task and subsequent dissociation from the physical effort. Response speed generally improved with exercise duration, while there was evidence of impaired accuracy in the early stages of the first half and the latter stages of the second half. CONCLUSION: The interaction of physical and mental work was not additive in nature. The mental task had a masking effect on the physical response. Performing physical exercise tasks without due regard for appropriate psychological stimuli may therefore overestimate the physiological response.
Assuntos
Cognição/fisiologia , Futebol/fisiologia , Adulto , Teste de Esforço/métodos , Frequência Cardíaca/fisiologia , Humanos , Hidrocortisona/metabolismo , Ácido Láctico/sangue , Masculino , Esforço Físico/fisiologia , Tempo de Reação , Análise e Desempenho de TarefasRESUMO
In multiple myeloma, changes in serum-free immunoglobulin light chains (FLC) are a more rapid indicator of treatment response than intact immunoglobulin due to their shorter serum half-life. The present study analysed the changes in serum FLC after autologous peripheral blood stem cell transplantation (PBSCT) in 19 patients. The majority of myeloma patients (18 of 19) undergoing PBSCT had a rapid fall in FLC concentrations. In all 11 of 19 patients with raised tumor FLC, it fell within 48 h following high-dose melphalan. In patients with monoclonal intact immunoglobulin, the tumor FLC fell quicker (median half-life 4.3 days) than the monoclonal intact immunoglobulin (median half-life 14 days). FLC recovery occurred after (13 of 19) or around the time of neutrophil engraftment (6 of 19). With a median follow up of 220 days post-transplant, 16 of 19 patients have a normal FLC ratio and 3 of 19 have an elevated tumor FLC/abnormal ratio. FLC assays provided a sensitive monitor of changes in tumor and non-tumor plasma cells after PBSCT. This assay is potentially valuable as a marker of chemosensitivity, as an indicator of residual tumor and indicated time to lymphocyte engraftment. Further follow-up is required to ascertain whether differences in the kinetics of FLC responses have any prognostic clinical utility.
Assuntos
Cadeias Leves de Imunoglobulina/sangue , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Neoplasia Residual/sangue , Neoplasia Residual/diagnóstico , Transplante de Células-Tronco de Sangue Periférico , Adulto , Idoso , Biomarcadores Tumorais/sangue , Feminino , Humanos , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Fatores de Tempo , Transplante Autólogo , Resultado do TratamentoRESUMO
Blastic plasmacytoid dendritic cell neoplasm is a rare, aggressive tumor characterized by skin and/or marrow infiltration by CD4(+) CD56(+) cells. Historically, the tumor was variably thought to arise from either monocytes, T cells or NK cells giving rise to terms such as CD4(+)/CD56(+) acute monoblastic leukemia, primary cutaneous CD4(+)/CD56(+) hematodermic tumor and blastic NK-cell lymphoma. Whilst considerable progress has been made in understanding the histogenesis, the best modality of treatment remains to be defined. We are therefore reporting this case which was successfully treated with a T-deplete allogeneic transplant and the patient is currently alive and in remission 4 years post transplant.
Assuntos
Alemtuzumab/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Linfoma/patologia , Linfoma/terapia , Condicionamento Pré-Transplante , Causas de Morte , Resistencia a Medicamentos Antineoplásicos , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Linfoma/mortalidade , Masculino , Prognóstico , Recidiva , Retratamento , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do TratamentoRESUMO
We report results in 41 consecutive patients with chronic lymphocytic leukemia (CLL) who underwent allogeneic hematopoietic cell transplantation (HCT) after fludarabine, melphalan, and alemtuzumab conditioning. Donors were 24 HLA-matched siblings and 17 unrelated volunteers, 4 of them mismatched with recipients. All but 3 patients had initial hematologic recovery, but 5 more patients had secondary graft failure. Median intervals to neutrophil (greater than 0.5 x 10(9)/L) and platelet (greater than 20 x 10(9)/L) recovery were 14 days (range, 9-30 days) and 11 days (range, 8-45 days), respectively. Eleven (27%) patients had relapses and received escalated donor lymphocyte infusions, but only 3 of them had sustained responses. Acute and chronic graft-versus-host disease (GVHD) was observed in 17 (41%) and 13 (33%) patients, respectively. Seventeen (41%) patients have died, 5 of progressive disease. The 2-year overall survival and transplantation-related mortality (TRM) rates were 51% (95% confidence interval [CI], 33%-69%) and 26% (95% CI, 14%-46%), respectively. The alemtuzumabbased regimen was feasible and effective in patients with CLL with a relatively low rate of GVHD. However, TRM remains relatively high as a result of a variety of viral and fungal infections. Studies are ongoing to address the efficacy of reduced doses of alemtuzumab in this group of immunosuppressed patients.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Transplante de Células-Tronco , Adulto , Idoso , Alemtuzumab , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Seguimentos , Doença Enxerto-Hospedeiro/prevenção & controle , Teste de Histocompatibilidade , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Pessoa de Meia-Idade , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Análise de Sobrevida , Fatores de Tempo , Doadores de Tecidos , Quimeras de Transplante , Transplante Homólogo/imunologia , Falha de Tratamento , Resultado do TratamentoRESUMO
Syndecan-1 (CD138) is a heparin sulphate proteoglycan that is over expressed on the surface of both normal and malignant plasma cells and actively shed from the cell surface (soluble syndecan-1). Soluble syndecan-1 has been shown to be an independent prognostic factor in myeloma but its role in prognostic classification requires further investigation. We have retrospectively measured soluble syndecan-1 in 324 presentation samples and 154 plateau phase samples from the UK Medical Research Council Myeloma VIth trial. Log-rank analysis showed that the presentation value of soluble syndecan-1 is a highly significant prognostic factor when assessing survival from entry (chi2=14.92, P<0.0001) and remains an important independent prognostic factor when considered in Cox regression models (PAssuntos
Biomarcadores Tumorais/sangue
, Glicoproteínas de Membrana/sangue
, Mieloma Múltiplo/sangue
, Proteoglicanas/sangue
, Idoso
, Distribuição de Qui-Quadrado
, Intervalo Livre de Doença
, Feminino
, Seguimentos
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Mieloma Múltiplo/mortalidade
, Prognóstico
, Estudos Retrospectivos
, Taxa de Sobrevida
, Sindecana-1
, Sindecanas