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1.
Bone Marrow Transplant ; 46(2): 262-6, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20479706

RESUMO

The standard approach for relapsed diffuse large B-cell lymphoma (DLBCL) involves auto-SCT. However, studies that established this approach were conducted before the inclusion of rituximab (R) with first-line therapy became routine. Whether DLBCL patients (pts) relapsing after first-line chemoimmunotherapy including R derive a comparable benefit from auto-SCT to pts in the pre-R era is unknown. We analyzed outcomes after auto-SCT for relapsed DLBCL among pts receiving initial R and those who did not. We reviewed 257 consecutive pts with relapsed DLBCL treated at our institution with auto-SCT. In all, 226 pts were included in the analysis, of whom 161 had received no R and 65 received R as part of first-line therapy (Planned R). Median OS and relapse-free survival, measured from transplant, were similar between No R vs Planned R groups: 67 vs 44 months (P=0.3) and 25 vs 27 months (P=0.8), respectively. A further analysis was carried out between two cohorts matched by propensity analysis. Again, no differences in outcomes were observed. This suggests that auto-SCT may be equally effective in pts relapsing after first-line therapy including R, and should remain the standard of care for relapsed DLBCL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B/terapia , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Recidiva , Estudos Retrospectivos , Rituximab , Transplante Autólogo , Resultado do Tratamento , Vincristina/administração & dosagem
2.
Ann Oncol ; 21(6): 1196-1202, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19875761

RESUMO

BACKGROUND: The purpose was to examine the prognostic impact of features of tumor cells and immune microenvironment in patients with follicular lymphoma treated with and without anti-CD20 monoclonal antibody therapy. PATIENTS AND METHODS: Tissue microarrays were constructed from archived tissue obtained from patients on three sequential Southwest Oncology Group (SWOG) trials for FL. All three trials included anthracycline-based chemotherapy. Anti-CD20 monoclonal antibodies were included for patients in the latter two trials. Immunohistochemistry was used to study the number and distribution of cells staining for forkhead box protein P3 (FOXP3) and lymphoma-associated macrophages (LAMs) and the number of lymphoma cells staining for myeloma-associated antigen-1 (MUM-1). Cox proportional hazards regression was used to evaluate the association between marker expression and overall survival (OS). RESULTS: The number or pattern of infiltrating FOXP3 cells and LAMs did not correlate with OS in sequential SWOG studies for FL. The presence of MUM-1 correlated with lower OS for patients who received monoclonal antibody but not for those treated with chemotherapy alone. CONCLUSIONS: Immune cell composition of lymph nodes did not correlate with OS in this analysis of trials in FL. The mechanism of the observed correlation between MUM-1 expression and adverse prognosis in patients receiving monoclonal antibody therapy requires confirmation.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Fatores Reguladores de Interferon/metabolismo , Linfoma Folicular/diagnóstico , Linfoma Folicular/terapia , Macrófagos/patologia , Linfócitos T Reguladores/patologia , Adulto , Idoso , Contagem de Células Sanguíneas , Ensaios Clínicos Fase II como Assunto , Terapia Combinada , Feminino , Humanos , Imunoterapia/métodos , Linfoma Folicular/imunologia , Linfoma Folicular/metabolismo , Macrófagos/metabolismo , Masculino , Oncologia/métodos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sudoeste dos Estados Unidos , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo
3.
Bone Marrow Transplant ; 40(10): 973-8, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17873917

RESUMO

Autologous stem-cell transplantation (ASCT) has been used in follicular lymphoma (FL) to achieve durable responses in first remission or in the relapsed or refractory settings. Addition of rituximab to chemotherapy for FL has been shown to improve survival. The impact of prior therapy with rituximab upon the effectiveness of high-dose therapy (HDT) and ASCT in patients with FL is unknown. We retrospectively reviewed consecutive patients with FL who underwent HDT and ASCT. Patients were categorized according to prior therapy with rituximab. Outcomes were compared between groups in all patients and in a well-matched subset. In all 35 patients received prior rituximab and 71 rituximab-naive patients were analyzed. The rituximab-naive group had a median overall survival (OS) that was not reached during follow-up, with a median relapse-free (RFS) survival of 49.9 months. The prior rituximab group also did not reach median OS and had a median RFS of 24.6 months. Survivals were not significantly different in this group or in the well-matched subset. In conclusion, these results suggest that the use of rituximab-based regimens for the treatment of FL does not compromise the effectiveness of HDT and ASCT as a salvage strategy in patients with FL.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Linfoma Folicular/terapia , Transplante de Células-Tronco de Sangue Periférico , Adulto , Anticorpos Monoclonais Murinos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rituximab , Transplante Autólogo
4.
Bone Marrow Transplant ; 40(5): 437-41, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17618321

RESUMO

The cellular composition of an autologous graft may influence autologous stem cell transplantation (ASCT) outcome. Etoposide (VP) plus filgrastim (G) frequently mobilizes high numbers of CD34+ cells for autologous transplantation. We investigated whether patients collecting high numbers of CD34+ cells ('super mobilizers') have a better outcome than other patients. We reviewed 350 consecutive adult patients with NHL or Hodgkin's lymphoma receiving an ASCT from January 1994 to December 2005, mobilized with VP+G. Super mobilizers were defined as collecting a minimum of 8 x 10(6) CD34+ cells/kg. Two hundred and three patients were super mobilizers, while 147 collected between 2.0 and 7.95 CD34+ cells/kg. Super mobilizers were younger and more likely to have received two or fewer prior chemotherapy regimens (80 versus 63%, P<0.001). Median CD34+ cell dose for the super mobilizing group was 13.7 x 10(6) versus 4.4 x 10(6)/kg in the standard collecting group. The super mobilizer group had a superior overall survival (P=0.006). In multivariable analysis, favorable disease status and younger age at transplant, and super mobilization were associated with improved survival. We conclude that patients had an improved ASCT outcome if large numbers of CD34+ cells were mobilized and infused. The explanation for this observation is unknown.


Assuntos
Antígenos CD34 , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/normas , Células-Tronco Hematopoéticas/citologia , Linfoma/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Coleta de Dados , Humanos , Contagem de Leucócitos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo , Resultado do Tratamento
5.
Bone Marrow Transplant ; 40(3): 239-43, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17530000

RESUMO

The role of high-dose therapy and autologous stem cell transplantation (ASCT) for patients with peripheral T-cell lymphoma (PTCL) is poorly defined. Comparisons of outcomes between PTCL and B-cell non-Hodgkin's lymphoma (NHL) have yielded conflicting results, in part due to the rarity and heterogeneity of PTCL. Some retrospective studies have found comparable survival rates for patients with T- and B-cell NHL. In this study, we report our single-center experience of ASCT over one decade using a uniform chemotherapy-only high-dose regimen. Thirty-two patients with PTCL-unspecified (PTCL-u; 11 patients) and anaplastic large-cell lymphoma (21 patients) underwent autologous stem cell transplant, mostly for relapsed or refractory disease. The preparative regimen consisted of busulfan, etoposide and cyclophosphamide. Kaplan-Meier 5-year overall survival (OS) and relapse-free survival (RFS) are 34 and 18%, respectively. These results suggest a poor outcome for patients with PTCL after ASCT, and new therapies for T-cell lymphoma are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T/mortalidade , Linfoma de Células T/terapia , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Bussulfano/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Linfoma de Células B/mortalidade , Linfoma de Células B/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo
6.
Br J Haematol ; 137(5): 436-42, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17433027

RESUMO

Granulocyte colony-stimulating factor (G-CSF) is widely used following myeloablative chemotherapy (high-dose therapy; HDT) and peripheral blood progenitor cell rescue (PBPCR) to reduce neutrophil engraftment time. The dose and duration required to gain maximum clinical and economic benefit has not been fully investigated. This double blind placebo-controlled randomised trial was performed to determine whether short course low-dose or standard-dose Lenograstim (L) would influence recovery of haematopoiesis following HDT and PBPCR. Sixty-one patients were randomised between May 1999 and November 2004, to receive standard-dose lenograstim (263 microg/d), low-dose lenograstim (105 microg/d) or placebo injections. These commenced on day +5 following PBPCR and continued until neutrophil engraftment [absolute neutrophil count (ANC)] > or = 0.5 x 10(9)/l. Patients received standard supportive care until haemopoietic recovery. Both standard- and low-dose lenograstim resulted in a significantly shorter median time to neutrophil recovery (ANC > or = 0.1 x 10(9)/l:10.0 vs. 11.0 d, P = 0.025; ANC > or = 0.5 x 10(9)/l:11.0 vs. 14.0 d, P = 0.0002) compared with placebo. There was no significant difference in blood product support, antibiotic usage, documented infection, overall survival or relapse-free survival between the groups. Short course low-dose lenograstim is as effective as standard-dose in reducing neutrophil engraftment time following HDT and PBPCR.


Assuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Neutrófilos/patologia , Transplante de Células-Tronco de Sangue Periférico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contagem de Células Sanguíneas , Terapia Combinada , Intervalo Livre de Doença , Método Duplo-Cego , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/cirurgia , Humanos , Lenograstim , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico
7.
Bone Marrow Transplant ; 36(5): 443-51, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15995712

RESUMO

We report outcomes in advanced lymphoma patients (n = 32) who enrolled in a trial of prospectively planned combined autologous/reduced-intensity transplantation (RIT) (n = 25) or who received RIT shortly after prior autografting because of high relapse risk or progressive disease (n = 7). Nine patients on the autologous/RIT transplant protocol did not proceed to planned RIT because of patient choice (n = 4), disease progression (n = 3), toxicity (n = 1), or no adequate donor (n = 1). Among the 23 other patients, RIT was started a median of 59 days (range 31-123) after autologous transplant. Fifteen patients had related donors, five patients had unrelated donors, and three patients had cord blood donors. Among all patients completing RIT, the median overall survival time was 385 days (95% CI 272-792), and the median relapse-free survival time was 157 days (95% CI 119-385). At the time of reporting, six patients (26%) remain alive and three patients (13%) remain alive without relapse. The 100-day transplant-related mortality (TRM) was 9% among all patients and was 0% among matched sibling donors. Overall TRM was 43%. Tandem transplant is feasible in advanced lymphoma with low early TRM. However, practical challenges associated with the strategy were significant and high levels of late TRM due to graft-versus-host disease and infections suggest that modifications of the procedure will be needed to improve outcomes and patient retention.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Transplante de Células-Tronco Hematopoéticas , Doadores Vivos , Linfoma/terapia , Condicionamento Pré-Transplante , Adulto , Idoso , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento
8.
Eur J Nucl Med Mol Imaging ; 30 Suppl 1: S19-27, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12721766

RESUMO

Advances in the treatment of Hodgkin's disease (HD) have resulted in cure rates of greater than 80%. This remarkable achievement has occurred in the past 50 years secondary to improvements in combination chemotherapy and radiotherapy. Over the last several decades, with the increase in long-term survivors of HD, it has become evident that cure is not the only issue, and late side-effects of treatment, including secondary malignancies and impaired fertility, are of major concern as well. As a result, attempts to improve response and survival rates by intensifying therapy must be countered against the potential for long-term toxicity.


Assuntos
Doença de Hodgkin/terapia , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/patologia , Humanos , Masculino , Estadiamento de Neoplasias , Segunda Neoplasia Primária/etiologia , Prognóstico , Radioterapia Adjuvante , Recidiva , Indução de Remissão , Transplante Autólogo , Transplante Homólogo
9.
J Clin Oncol ; 19(11): 2927-36, 2001 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-11387366

RESUMO

PURPOSE: To determine whether a combination of high-dose therapy and autologous stem-cell transplantation (ASCT) is superior to conventional-dose consolidation and maintenance chemotherapy as postremission therapy in adults with lymphoblastic lymphoma. PATIENTS AND METHODS: One hundred nineteen patients were entered onto this prospective randomized trial from 37 centers. Patients received standard remission induction therapy, and responding patients were randomized either to continue with a conventional consolidation/maintenance protocol (CC) or to receive high-dose therapy and ASCT. In some centers, patients with HLA-identical sibling donors were registered on the trial but proceeded to allogeneic bone marrow transplantation (BMT) without randomization. RESULTS: Of the 119 patients entered, 111 were assessable for response to induction therapy. The overall response rate was 82% (56% complete response, 26% partial response). Of the 98 patients eligible for randomization, 65 were randomized, 31 to ASCT and 34 to CC. Reasons for failure to randomize included patient refusal (12 patients), early progression or death on induction therapy (eight patients), excessive toxicity of induction regimen (six patients), and elective allogeneic BMT (12 patients). With a median follow-up of 37 months, the actuarial 3-year relapse-free survival rate is 24% for the CC arm and 55% for the ASCT arm (hazards ratio = 0.55 in favor of the ASCT arm; 95% confidence interval [CI], 0.29 to 1.04; P =.065). The corresponding figures for overall survival are 45% and 56%, respectively (hazards ratio = 0.87 in favor of the ASCT arm; 95% CI, 0.42 to 1.81; P =.71). CONCLUSION: The use of ASCT in adults with lymphoblastic lymphoma in first remission produced a trend for improved relapse-free survival but did not improve overall survival compared with conventional-dose therapy in this small randomized trial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Idoso , Transplante de Medula Óssea , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Estudos Prospectivos , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento
10.
Bone Marrow Transplant ; 28(9): 813-20, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11781640

RESUMO

The outlook for patients with mantle cell lymphoma is poor. The reported median survival in most published series is only 3 to 4 years, and even the most favorable prognostic groups have median survival rates of only 5 years, with no evidence of cure. The use of autologous and allogeneic stem cell transplantation in this disease has increased dramatically in recent years. Despite encouraging reports from single centers and registries, the impact of stem cell transplantation on the outcome for mantle cell lymphoma is unclear. Optimal first-line regimens for mantle cell lymphoma have yet to be defined, and it is therefore difficult to place the role of first remission transplantation in an appropriate context. Prospective randomized trials have been difficult to design and conduct in the absence of a well-defined 'standard' treatment. The role of stem cell transplantation as a salvage strategy is also unknown, although available data suggest that it does not improve survival in heavily pre-treated patients. In the absence of clear evidence for a survival advantage for patients receiving stem cell transplants for mantle cell lymphoma, entry into clinical trials should be a priority.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Célula do Manto/terapia , Análise Atuarial , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Purging da Medula Óssea , Ensaios Clínicos como Assunto , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Indução de Remissão , Terapia de Salvação , Análise de Sobrevida , Taxa de Sobrevida , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento
11.
Ann Oncol ; 11(7): 861-5, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10997815

RESUMO

BACKGROUND: 'Molecular response' is being investigated as a therapeutic goal in follicular lymphoma (FL). High response rates in FL with the fludarabine combination 'FMD' have been associated with 'molecular remission'. A phase II study of FMD in FL was therefore conducted. PATIENTS AND METHODS: Fifty-four patients, ten of whom were newly diagnosed received FMD. Forty-four percent of the previously treated patients had 'chemoresistant' disease. Treatment comprised: fludarabine 25 mg/m2 days 1-3, mitoxantrone 10 mg/m2 day 1, and dexamethasone 20 mg days 1-5. Blood/bone marrow was collected for quantitation of t(14;18) by 'real-time' PCR. RESULTS: The overall response rate was 37 of 54 (69%), complete responses being seen in 11 patients (20%), with no difference between newly diagnosed and the previously treated patients. However, the response rate in 'chemosensitive' relapse was 84% compared to 44% in patients in whom the last prior regimen had failed. Molecular responses were seen in 17 of 25 and PCR negativity in 8 of 25, although molecular and clinical responses did not always correlate. Toxicity was moderate, 19 patients required admission. However, in 6 of 12 patients, subsequent G-CSF mobilised stem cell harvests failed. CONCLUSIONS: FMD was well tolerated but with a lower than expected response rate. Molecular responses were seen in the majority of responding patients however, 'molecular remission' was rare.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Vidarabina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , DNA de Neoplasias/análise , Dexametasona/administração & dosagem , Feminino , Humanos , Linfoma Folicular/genética , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Reação em Cadeia da Polimerase , Recidiva , Resultado do Tratamento , Vidarabina/administração & dosagem
12.
Br J Haematol ; 109(1): 81-8, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10848785

RESUMO

Follicular lymphoma (FL) cells express CD20 and are associated in most cases with the t(14;18) chromosomal translocation. A multicentre study was undertaken between January 1997 and January 1998 to assess the complete response rate (CR) and overall response rate (RR) to rituximab, a chimaeric anti-CD20 monoclonal antibody. Seventy patients with previously treated FL received rituximab (375 mg/m2/week x4, by intravenous infusion). Restaging studies were performed 1 and 2 months after therapy. Molecular monitoring for the presence of cells harbouring the Bcl-2/JH gene rearrangement in the peripheral blood (PB) and bone marrow (BM) was performed before and after treatment using a two-step semi-nested polymerase chain reaction (PCR) assay. The overall RR was 32/70 (46%), being highest in patients who had received only one previous treatment (12/15, 80%). However, only two patients achieved a CR. The median duration of response was 11 months. Thirteen of 21 evaluable 'PCR-positive' patients (62%) became 'PCR-negative' in PB and/or BM samples 1 month after rituximab, although this did not correlate with clinical response. Treatment was generally well tolerated, although one patient developed Stevens-Johnson syndrome. Rituximab was shown to be active in FL, and in some cases PB and/or BM became PCR negative. Studies in combination with cytotoxic chemotherapy to increase the CR rate are warranted.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos CD20/imunologia , Linfoma Folicular/tratamento farmacológico , Adulto , Idoso , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos , Feminino , Seguimentos , Rearranjo Gênico , Genes bcl-2 , Humanos , Linfoma Folicular/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Proteínas Recombinantes de Fusão/uso terapêutico , Rituximab , Resultado do Tratamento
13.
J Hematother Stem Cell Res ; 9(2): 219-23, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10813535

RESUMO

The traditional indicators of engraftment following PBSC transplantation (PBSCT) are the rising total WBC count and ANC. Reticulocytes may be an earlier indicator, since as reticulocytes mature, there is a gradual loss of cellular RNA, which can be measured using methylene blue and light scatter with an Abbott CD 3500 automated counter (Abbott Laboratories, Maidenhead, U.K.). Reticulocytes can be divided into three fluorescence ratios depending on the amount of light scatter generated, high, medium, and low. The most immature are the high fluorescence reticulocytes (HFR). Standard engraftment parameters together with HFR were measured in a homogeneous group of 25 patients with lymphoma after PBSCT using a standard conditioning protocol. An ANC of 0.5 x 10(9)/L was achieved after a median of 10 days (mean 11.2 days, range 9-22). The recovery of the HFR to 2% of the total reticulocytes was significantly shorter, with a median of 8 days (mean 7.5 days, range 6-10) (p < 0.0001). The values of HFR to 2% preceded the ANC of 0.5 x 10(9)/L in 24 of the 25 patients by a median of 3 days (mean 3.8 days, range 2-12 days). On this basis, it can be determined that in 96% of cases, engraftment was indicated earlier by HFR measurement. The HFR to 2% even preceded the ANC of 0.1 x 10(9)/L in 23 of the 25 patients, showing that engraftment was indicated earlier in 92% of patients. Immature reticulocytes appearing in peripheral blood can be reliably measured by automated cytometers, and HFR can, therefore, be used as an earlier indicator of engraftment following PBSCT. This information provides the opportunity for earlier cessation of antibiotics and growth factors and could lead to earlier discharge from hospital, with cost savings.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas , Linfoma/terapia , Adulto , Antineoplásicos/uso terapêutico , Automação , Biomarcadores/análise , Biomarcadores/sangue , Carmustina/administração & dosagem , Citarabina/administração & dosagem , Feminino , Citometria de Fluxo , Humanos , Linfoma/sangue , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Neutrófilos/citologia , Podofilotoxina/administração & dosagem , Valor Preditivo dos Testes , Contagem de Reticulócitos/instrumentação , Reticulócitos/química , Reticulócitos/citologia , Fatores de Tempo , Transplante Autólogo
14.
J Clin Oncol ; 18(4): 795-803, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10673521

RESUMO

PURPOSE: We report the clinical features and treatment of 31 patients with a diagnosis of enteropathy-type intestinal T-cell lymphoma treated at the Wessex Regional Medical Oncology Unit in Southampton between 1979 and 1996 (23 men, eight women). PATIENTS AND METHODS: Patients were identified from our lymphoma database. Details of history, physical examination, staging investigations, treatment, and outcome were taken from patient records. RESULTS: Twelve patients (35%) had a documented clinical history of adult-onset celiac disease, and a further three had histologic features consistent with celiac disease in resected areas of the small bowel not infiltrated with lymphoma. After diagnosis, 24 (77%) of the 31 patients were treated with chemotherapy; the remaining seven had surgical treatment alone. More than half were unable to complete their planned chemotherapy courses, often because of poor nutritional status; 12 patients required enteral or parenteral feeding. A response to initial chemotherapy was observed in 14 patients (complete response, n = 10; partial response, n = 4). Observed complications of treatment were gastrointestinal bleeding, small-bowel perforation, and the development of enterocolic fistulae. Relapses occurred 1 to 60 months from diagnosis in 79% of those who responded to initial therapy. Of the total 31 patients, 26 (84%) have died, all from progressive disease or from complications of the disease and/or its treatment. The actuarial 1- and 5-year survival rates are 38.7% and 19.7%, respectively, with 1- and 5-year failure-free survival rates of 19.4% and 3.2%, respectively. CONCLUSION: The prognosis for these patients is poor. This, in part, reflects late diagnosis and poor performance status at the time of presentation. The role of salvage treatments and high-dose chemotherapy at relapse is not clear. However, it is encouraging that there are five long-term survivors in our patient population.


Assuntos
Neoplasias Intestinais/diagnóstico , Linfoma de Células T/diagnóstico , Análise Atuarial , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Celíaca/patologia , Progressão da Doença , Intervalo Livre de Doença , Nutrição Enteral , Feminino , Seguimentos , Humanos , Neoplasias Intestinais/patologia , Neoplasias Intestinais/cirurgia , Neoplasias Intestinais/terapia , Intestino Delgado/patologia , Linfoma de Células T/patologia , Linfoma de Células T/cirurgia , Linfoma de Células T/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estado Nutricional , Nutrição Parenteral , Exame Físico , Complicações Pós-Operatórias , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
16.
Ann Oncol ; 10(9): 1121-4, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10572614

RESUMO

BACKGROUND: The clinical applicability of the Revised European-American Lymphoma (R.E.A.L.) Classification has been demonstrated in several retrospective studies. The present, ongoing study was initiated to evaluate the clinical and pathological utility of the R.E.A.L. Classification compared with the Working Formulation (WF) in a prospective fashion, in an unselected patient population treated at a single institution. PATIENTS AND METHODS: Prospective data were collected on 596 biopsies from 557 patients referred with an initial diagnosis of lymphoma. After initial histologic review, 465 biopsies from 441 patients were confirmed as non-Hodgkin's lyphoma (NHL), 412 of which could be classified in R.E.A.L. and WF. RESULTS: According to WF criteria, 25% were low grade, 58% intermediate grade and 2% high grade, 14% could not be allocated to a WF subtype. According to R.E.A.L., 46% were diffuse large B cell, 19% follicle centre lymphoma, 6% marginal zone, 6% small lymphocytic, 4% mantle cell, and 3% T-cell anaplastic large cell. For those with B-cell NHL, 7% were unclassifiable in WF compared with 1% in R.E.A.L. Corresponding figures for T-cell NHL were 68% and 3%, respectively. CONCLUSIONS: Preliminary results confirm the clinical utility of the R.E.A.L. Classification in a single institution setting, demonstrating that cases were more readily sub-typed in R.E.A.L. compared with WF. Frequencies are comparable with I.L.S.G. data. Further follow up with large patient numbers is on-going to analyse survival data with reference to clinical prognostic factors.


Assuntos
Linfoma não Hodgkin/classificação , Linfoma não Hodgkin/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Guias como Assunto , Histologia/classificação , Humanos , Linfoma de Células B/classificação , Linfoma de Células B/diagnóstico , Linfoma de Células B/patologia , Linfoma não Hodgkin/patologia , Linfoma de Células T/classificação , Linfoma de Células T/diagnóstico , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
J Clin Oncol ; 17(10): 3101-9, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10506605

RESUMO

PURPOSE: To investigate the results of high-dose therapy and autologous stem-cell transplantation (ASCT) in adults with Hodgkin's disease who do not enter remission after induction therapy, to determine overall survival (OS) and progression free survival (PFS), and to identify prognostic factors. PATIENTS AND METHODS: A retrospective analysis of 175 patients reported to the European Group for Blood and Marrow Transplantation between November 1979 and October 1995. One hundred were male and 75 were female, with a median age of 26.5 years. Responses to first-line therapy were defined as progressive disease (PD) in 88 and stable/minimally responsive disease (SD/MR) in 87. Seventy-five patients received ASCT after failure of one induction regimen. Second-line therapy was given to the remaining 100 patients. Response to second-line therapy was PD in 34 and SD/MR in 66. OS and PFS rates were determined, and prognostic factors were investigated using univariate and multivariate analyses. RESULTS: Responses to high-dose therapy and ASCT were complete response (30%), partial response (28%), no response (14%), PD (14%), and toxic death (14%). Actuarial 5-year OS and PFS rates were 36% and 32%, respectively. In univariate analysis for PFS and OS, adverse factors were use of a second-line chemotherapy regimen and interval of more than 18 months between diagnosis and ASCT. In multivariate analysis, the interval between diagnosis and ASCT maintained prognostic significance for OS. Response to the chemotherapy regimen given immediately before ASCT had no predictive value. CONCLUSION: High-dose therapy and ASCT is an effective treatment strategy for patients with Hodgkin's disease for whom induction chemotherapy fails. Outcome was equivalent for those with obvious PD or SD/MR in response to the regimen given immediately before high-dose therapy. Prospective randomized studies are required to compare this approach with conventional-dose salvage therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Terapia de Salvação , Análise de Sobrevida , Resultado do Tratamento
19.
Blood ; 91(11): 4292-9, 1998 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-9596678

RESUMO

Investigations of VH gene mutational patterns in B-cell tumors are often performed at an arbitrary time point of disease. To assess the effects of disease progression, tumor-derived VH genes have been monitored from presentation through treatment and relapse in one patient with follicle center lymphoma (FCL), and two patients with primary diffuse large B-cell lymphoma (DLCL). The patient with FCL and one patient with DLCL both achieved clinical remission, although this was only partial in the FCL. However, both subsequently relapsed, and the second patient with DLCL was refractory to radiotherapy and chemotherapy. In each case, the tumor-derived VH sequence was identified, and the CDR3 "clonal signature" was used to track tumor cell sequences in subsequent biopsies. All cases showed somatic mutations, with intraclonal heterogeneity evident at presentation, and some sequences were aberrant. The VH sequences of the DLCL which responded to treatment became homogeneous at relapse. The sequences of both the FCL and the refractory DLCL remained heterogeneous. In all cases, transcripts of multiple Ig isotypes could be identified, and there was immunophenotypic evidence for expression of several Ig isotypes. The case of refractory DLCL had identifiable transcripts from IgM, IgD, IgA, IgG, and IgE, but appeared to lose the ability to produce alternative isotype transcripts and protein at the late stage of disease. These cases indicate that VH gene analysis can be used to probe tumor cell behavior in cases of lymphoma and that perturbations caused by therapy and disease progression can occur.


Assuntos
Genes de Imunoglobulinas , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Linfoma de Células B/genética , Linfoma Folicular/genética , Linfoma Difuso de Grandes Células B/genética , Transcrição Gênica , Sequência de Aminoácidos , Sequência de Bases , Biópsia , Progressão da Doença , Humanos , Cadeias Pesadas de Imunoglobulinas/química , Isotipos de Imunoglobulinas/genética , Região Variável de Imunoglobulina/química , Imunofenotipagem , Linfoma de Células B/patologia , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/patologia , Dados de Sequência Molecular , Mutação
20.
Br J Haematol ; 100(1): 112-22, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9450799

RESUMO

We used flow cytometry to characterize cell adhesion molecule expression of the human haemopoietic cell lines KG1a, K562, HL-60, NALM-6 and CEM. A 51chromium labelling assay was used to study the adhesion of these cell lines to extracellular matrix components and to bone marrow stromal and endothelial cultures. Both adhesion molecule expression and functional binding behaviour varied between cell lines. All five cell lines expressed the integrins alpha4beta1 and alpha5beta1 and all adhered to fibronectin. However, differences in intensity of expression of these integrins failed to correlate with extent of fibronectin adhesion. Inhibition experiments demonstrated that adhesion of KG1a to fibronectin was completely inhibited by divalent cation chelation and partially inhibited by RGDS peptides and chondroitinase ABC, suggesting that both alpha4beta1 and alpha5beta1 as well as CD44 were responsible for this interaction. Adhesion to bone marrow stromal and endothelial layers was superior to that to purified extracellular matrix components and was partially inhibited by divalent cation chelation. RGD peptides and anti-alpha4 monoclonal antibody also partially inhibited KG1a adhesion to bone marrow endothelium. Discordance between cell adhesion molecule expression and adhesive behaviour suggest that current phenotypic descriptions remain incomplete and reinforce the need for complementary functional binding studies.


Assuntos
Células da Medula Óssea/metabolismo , Moléculas de Adesão Celular/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Antígenos CD/metabolismo , Adesão Celular , Quelantes/metabolismo , Endotélio/metabolismo , Matriz Extracelular/metabolismo , Humanos , Células Estromais/metabolismo , Células Tumorais Cultivadas
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