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BACKGROUND: Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have limited treatment options. METHODS: R/R DLBCL patients, who were mostly ineligible for ASCT due to age or comorbidities, were treated with maveropepimut-S (MVP-S, previously DPX-Survivac) a survivin directed T cell educating therapy, pembrolizumab, and intermittent low-dose cyclophosphamide. FINDINGS: We identified, using univariate analysis, a subset of patients with enhanced ORR, PFS and DOR. Patients with baseline CD20+/PD-L1 expression had an ORR of 46% (6/13) and the disease control rate was 10/13 (77%). The PFS and OS of the positive CD20+/PD-L1 patients were 7.1 months and 17.4 months, whereas in the intent-to-treat (ITT) population of 25 enrolled patients, the ORR was 28% (7/25), median PFS and OS were 4.2 months and 10.1 months respectively. A total of 6/7 clinical responders occurred in CD20+/PD-L1 patients. The regimen was well-tolerated, requiring only minor dose modifications and one discontinuation. Grade 1 or 2 injection site reactions occurred in 14/25, (56%). Statistically significant associations were also seen between PFS and; injection site reactions; and ELISpot response to survivin peptides, both identifying the mechanistic importance of specific immune responses to survivin. INTERPRETATION: This immunotherapy combination was found to be active and safe in this clinically challenging patient population.
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Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Survivina/uso terapêutico , Antígeno B7-H1/metabolismo , Reação no Local da Injeção , Linfoma não Hodgkin/tratamento farmacológico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologiaRESUMO
B-cell depletion may impair vaccine responses and increase infection risk in patients with immune thrombocytopenia (ITP). We investigated the effects of rituximab on antibody and cellular responses to Streptococcus pneumoniae polysaccharide and Haemophilus influenzae type b (Hib) vaccines in ITP patients. Of 60 patients in the main trial, 24 patients received both vaccines 6 months after rituximab (n = 17) or placebo (n = 7). Among 20 evaluable patients, 3 of 14 (21%) in the rituximab group and 4 of 6 (67%) in the placebo group achieved a fourfold increase in anti-pneumococcal antibodies (P = .12). For anti-Hib antibodies, 4 of 14 (29%) and 5 of 6 (83%), respectively, achieved a fourfold increase (P < .05). Fewer patients in the rituximab group demonstrated Hib killing (2 of 14 [14%], 5 of 6 [83%], P < .05). Three of 14 rituximab-treated patients failed to respond to vaccines by any criteria. After vaccinations, preplasma cell blasts and interferon-γ-secreting T cells were reduced in rituximab-treated patients. Antibody responses were impaired for at least 6 months after rituximab. Cellular immunity was reduced in parallel with depleted B-cell pools. These findings have implications for the timing of vaccinations and the mechanism of infection after rituximab in ITP patients.
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Anticorpos Monoclonais Murinos/uso terapêutico , Vacinas Anti-Haemophilus/uso terapêutico , Trombocitopenia/tratamento farmacológico , Adulto , Idoso , Anticorpos Antibacterianos/imunologia , Subpopulações de Linfócitos B/efeitos dos fármacos , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Cápsulas Bacterianas/imunologia , Terapia Combinada , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Vacinas Anti-Haemophilus/imunologia , Haemophilus influenzae tipo b/imunologia , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Rituximab , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Trombocitopenia/imunologia , Resultado do TratamentoRESUMO
OBJECTIVES: Many believe that knowledge of anatomy is essential for performing clinical procedures; however, unlike their surgical counterparts, internal medicine (IM) programs rarely incorporate anatomy review into procedural teaching. This study tested the hypothesis that an educational intervention focused on teaching relevant surface and underlying anatomy would result in improved bone marrow procedure landmarking accuracy. METHODS: This was a preintervention-postintervention prospective study on landmarking accuracy of consenting IM residents attending their mandatory academic half-day. The intervention included an interactive video and visualization exercise; the video was developed specifically to teach the relevant underlying anatomy and includes views of live volunteers, cadavers, and skeletons. RESULTS: Thirty-one IM residents participated. At pretest, 48% (15/31) of residents landmarked accurately. Inaccuracy of pretest landmarking varied widely (n = 16, mean 20.06 mm; standard deviation 30.03 mm). At posttest, 74% (23/31) of residents accurately performed the procedure. McNemar test revealed a nonsignificant trend toward increased performance at posttest (P = 0.076; unadjusted odds for discordant pairs 3; 95% confidence interval 0.97-9.3). The Wilcoxon signed rank test demonstrated a significant difference between pre- and posttest accuracy in the 16 residents who were inaccurate at pretest (P = 0.004). No association was detected between participant baseline characteristics and pretest accuracy. CONCLUSIONS: This study demonstrates that residents who were initially inaccurate were able to significantly improve their landmarking skills by interacting with an educational tool emphasizing the relation between the surface and underlying anatomy. Our results support the use of basic anatomy in teaching bone marrow procedures. Results also support the proper use of video as an effective means for incorporating anatomy teaching around procedural skills.
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Anatomia/educação , Medula Óssea , Medicina Interna/educação , Internato e Residência , Manejo de Espécimes/métodos , Ensino/métodos , Humanos , TatuagemRESUMO
This phase 1 study evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of obinutuzumab (GA101), a glycoengineered type II anti-CD20 monoclonal antibody administered as induction followed by 2 years of maintenance. Cohorts of 3 to 6 patients received obinutuzumab (200-2000 mg) intravenously weekly for 4 weeks. Patients with a complete or partial response (or stable disease and clinical benefit) continued to receive obinutuzumab every 3 months, for a maximum of 8 doses. Twenty-two patients with relapsed CD20-positive non-Hodgkin lymphoma or chronic lymphocytic leukemia with an indication for treatment and no therapy of higher priority were enrolled. Patients received a median of 4 prior regimens; 86% had received at least 1 rituximab-containing regimen. No dose-limiting or unexpected AEs were observed. Infusion-related reactions were most common (all grades, 73%; grade 3/4, 18%), followed by infection (32%), pyrexia (23%), neutropenia (23%), headache (18%), and nausea (18%). At end of induction, 5 (23%) patients achieved partial responses and 12 (54%) had stable disease. Eight patients received maintenance; best overall response was 32% (6 partial responses/1 complete response). Obinutuzumab induction and maintenance therapy was well tolerated with promising efficacy in this heterogeneous, highly pretreated population and warrants further investigation. This study was registered at www.clinicaltrials.gov (identifier NCT00576758).
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Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígenos CD20 , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The benefit of adding rituximab to standard treatment in nonsplenectomized patients with primary immune thrombocytopenia (ITP) is uncertain. We performed a pilot randomized trial to determine the feasibility of recruitment, protocol adherence, and blinding of a larger trial of rituximab versus placebo; and to evaluate the potential efficacy of adjuvant rituximab in ITP. Nonsplenectomized adults with newly diagnosed or relapsed ITP who were receiving standard ITP therapy for a platelet count below 30 × 10(9)/L were randomly allocated to receive 4 weekly infusions of 375 mg/m(2) rituximab or saline placebo. Sixty patients were recruited over 46 months, which was slower than anticipated. Protocol adherence and follow-up targets were achieved, and blinding was successful for research staff but not for patients. After 6 months, there was no difference between rituximab and placebo groups for the composite outcome of any platelet count below 50 × 10(9)/L, significant bleeding or rescue treatment once standard treatment was stopped (21/32 [65.6%] vs 21/26 [80.8%]; relative risk = 0.81, 95% confidence intervals, 0.59%-1.11%). Timely accrual poses a challenge to the conduct of a large randomized trial of rituximab for presplenectomy ITP. No difference in the frequency of the composite outcome was observed in this pilot trial (registered at www.clinicaltrials.gov NCT00372892).
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Anticorpos Monoclonais Murinos/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adulto , Anticorpos Monoclonais Murinos/efeitos adversos , Quimioterapia Adjuvante , Método Duplo-Cego , Fadiga/induzido quimicamente , Feminino , Seguimentos , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/induzido quimicamente , Projetos Piloto , Placebos , Contagem de Plaquetas , Rituximab , Esplenectomia , Resultado do TratamentoRESUMO
BACKGROUND: Patients with hematological cancers have increased COVID-19 morbidity and mortality, and these patients show attenuated vaccine responses. This study aimed to characterize the longitudinal humoral immune responses to COVID-19 vaccination in patients with hematological malignancies. PATIENTS AND METHODS: We conducted a prospective cohort study, collecting samples from March 2021 to July 2022, from patients seen at a cancer treatment center in London, Ontario, Canada, who met the following eligibility criteria: age ≥18 years, diagnosed with a hematological malignancy, recipient of a COVID-19 vaccine during the study period, and able to provide informed consent. RESULTS: Median anti-S titers (MST) were 0.0, 64.0, and 680.5 U/mL following first (V1), second (V2), and third (V3) vaccine doses, respectively. Patients with lymphoid malignancies' response to vaccination was attenuated compared to myeloid malignancy patients after V2 and V3 (P < .001, P < .01). Active treatment was associated with lower antibody titers (MST 10) compared to treatment 12-24 months (MST 465, P = .04367) and >24 months (MST 1660.5, P = .0025) prior to vaccination. V3 significantly increased antibody titers compared to V2 for patients less than 3 months from treatment. Increasing age was associated with smaller antibody response following V2 (P < .05), but not following V3. Patients receiving anti-CD20 therapy did not demonstrate increased antibody titer levels after V3 (V2 MST 0, V3 MST 0; P > .05). CONCLUSION: We report an attenuated serologic response to COVID-19 vaccination in our study population of patients with hematological malignancy. The immune response to vaccination was affected by patient age, diagnosis, treatment, and timing of treatment exposure.
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Vacinas contra COVID-19 , COVID-19 , Neoplasias Hematológicas , SARS-CoV-2 , Humanos , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/complicações , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/complicações , Idoso , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/uso terapêutico , SARS-CoV-2/imunologia , Adulto , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Vacinação , Idoso de 80 Anos ou mais , Imunidade HumoralRESUMO
BACKGROUND: Immune response to COVID-19 vaccine is diminished in patients with hematologic malignancy. There is limited data regarding response to vaccine doses in these patients. PURPOSE: To quantify the humoral immune response engendered by 4th and subsequent doses of SARS-CoV-2 vaccination as measured by anti-Spike (anti-S) antibody levels, based on dried blood spot (DBS) testing, in patients with hematologic malignancies. Anti-S binds to the spike protein of the SARS-CoV-2 virus and is indicative of vaccine immunogenicity. METHODS: We conducted a prospective study of hematologic malignancies between August 2021 and January 2023 at 12 sites across Canada. Participants were followed longitudinally and submitted finger-prick DBS cards at set intervals associated with vaccination. Samples were processed via high throughput ELISA assay to detect serum antibodies against nucleocapsid (N) and spike (S) proteins. RESULTS: We obtained 3071 samples on 790 unique patients. Of these, 372 unique participants with 1840 samples had anti-S results available post-4th, 5th or 6th COVID-19 vaccine dose and were included for analysis. Three hundred thirty-three patients of the 372 participants submitted a DBS sample post 4th dose. Of these, 257 patients (77.2%) had a positive anti-S antibody. A total of 198 patients had paired samples pre- and post-dose 4, of which 59 (29.7%) had a negative anti-S antibody pre-dose 4. Of these, 20 (33.4%) developed positive anti-S antibody post-dose 4. One hundred forty-nine patients submitted a DBS sample post-dose 5. Of these, 135 patients (90.6%) had positive anti-S antibody. A total of 52 had paired samples pre- and post-dose 5. Six (8.7%) had a negative anti-S antibody pre-dose 5, of which two (33.3%) developed positive anti-S antibody post-dose 5. Of these 372 patients, 123 (34%) reported COVID-19 infection and 4 (1%) had a COVID-19 related hospitalization. There were no reported deaths from COVID-19. CONCLUSIONS: This prospective cohort study showed that humoral immune response improved with subsequent doses of COVID-19 vaccines.
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Primary dural Hodgkin lymphoma (PDHL) is an extremely rare subset of Hodgkin lymphoma (HL). Its existence is controversial, as Hodgkin lymphoma is not traditionally thought to arise from the central nervous system (CNS) or its meninges and only 0.02% of patients with Hodgkin lymphoma have any CNS involvement. We report a case of a 71-year-old Caucasian man who presented with progressive fatigue and sudden onset slurred speech, disorientation, and memory loss. Brain imaging identified a large extra-axial right frontal mass, and he underwent urgent subtotal resection. Pathology and subsequent workup revealed Stage IAE classical Hodgkin lymphoma of the right frontal dura, with no extra-cranial disease or leptomeningeal spread detected. The patient was subsequently treated with ABVD chemotherapy (completed 2.5 of 4 planned cycles) and 36 Gy in 20 fractions of consolidative involved-site radiotherapy (ISRT). He has been followed for 5 years with no clinical or radiological signs of recurrence. This is the second confirmed case of intracranial PDHL reported in the literature, with the longest follow-up for any case of PDHL.
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BACKGROUND: Between March 2012 and March 2013, a miscommunication in labelling between the drug compounder supplier and cancer centre pharmacies resulted in accidental overdilution of cyclophosphamide and gemcitabine used by several cancer centres in Canada. At our centre, 177 hematology patients were affected, among whom the largest subset of patients was those with diffuse large B-cell lymphoma. In this study, we evaluated the effect of such underdosing on disease response. METHODS: We conducted a retrospective cohort study involving all patients with diffuse large B-cell lymphoma who received at least 1 chemotherapy cycle containing diluted cyclophosphamide at our centre and compared them with a historical group of patients matched by stage and age. The primary outcome was event-free survival (a composite of disease progression or death). Secondary outcomes included complete remission and overall response rate. Groups were compared using unpaired Student t, χ2 or Fisher exact tests, as appropriate. Survival analysis was done using the Kaplan-Meier method. RESULTS: Event-free survival was no different between groups (log-rank p = 0.99). At a median follow-up of 548 days, progression or death occurred in 21 of 77 patients in the case group (27.3%) and in 24 of 74 patients in the control group (32.4%) (p = 0.5). At the end of treatment, complete remission was achieved in 41 patients in the case group (53.2%) and 43 patients in the control group (57.3%) (p = 0.6), whereas overall response rate was 71.4% in the case group and 66.7% in the control group (p = 0.5). INTERPRETATION: Compared with a historical control group, we found no differences in event-free survival or response rates among patients with diffuse large B-cell lymphoma who received 1 or more doses of accidentally diluted cyclophosphamide-containing chemotherapy.
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Patients with mantle cell lymphoma (MCL) have a particularly poor prognosis when treated with standard chemotherapy, with a median overall survival of only 3 years. These patients have therefore been considered for first-line treatment with more aggressive or experimental strategies, such as high-dose therapy (HDT) with autologous stem cell transplantation (ASCT). While high rates of clinical remission have been achieved with HDT/ASCT, this procedure alone is not believed to be curative and different treatment strategies are being developed to improve outcomes in this group of patients. Single-agent rituximab is active in both newly diagnosed and relapsed MCL and therefore the addition of rituximab to chemotherapy regimens and/or HDT/ASCT may enhance their efficacy. Outside the transplantation setting, rituximab plus chemotherapy has been shown to be highly active in MCL, and preliminary data from randomized trials suggest that the combination may yield superior results compared with chemotherapy alone. The addition of rituximab to transplantation protocols appears to be a very promising strategy for patients with MCL, given as an in vivo purge before HDT/ASCT and/or as posttransplant maintenance therapy. Two phase II clinical trials with rituximab given as an in vivo purge during stem cell mobilization and as posttransplant immunotherapy in patients with previously untreated MCL have generated very promising data. Rituximab is an important addition to cytotoxic therapy and with HDT/ASCT represents a highly active therapy that may be superior to conventional treatment or HDT/ASCT alone in MCL. Randomized prospective studies and longer follow-up are needed to determine whether these regimens can achieve longer survival or possibly cure in this disease.
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Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Linfoma de Célula do Manto/terapia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Humanos , Linfoma de Célula do Manto/mortalidade , Rituximab , Transplante de Células-Tronco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Advanced-stage mantle cell lymphoma (MCL) is a disease for which no curative treatment strategy exists. Results with standard combination chemotherapy, with or without an anthracycline, are disappointing, and new and better therapies are needed. High-dose therapy and autologous stem-cell transplantation (ASCT) have been performed in patients with MCL both up front and at relapse with varying degrees of success. Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) has shown moderate response rates in patients with MCL. It has also been used safely and effectively as an in vivo purge during ASCT for patients with lymphoma. We are currently investigating an aggressive protocol in patients with newly diagnosed, untreated MCL using a combination of two promising therapeutic modalities, high-dose therapy-ASCT and rituximab. Since 1999, 13 patients with newly diagnosed MCL have been enrolled in this phase II clinical trial. CHOP (cyclophosphamide/prednisone/vincristine/doxorubicin) is used as debulking chemotherapy. Stem cells are mobilized with 5 days of granulocyte colony-stimulating factor 10 microg/kg/d, with a single infusion of rituximab 375 mg/m(2) used as an in vivo purge before stem-cell collection by large-volume leukapheresis. The transplant conditioning regimen is cyclophosphamide/carmustine/etoposide. Post-transplant consolidative immunotherapy consists of rituximab 375 mg/m(2), administered as two 4-week cycles at 2 and 6 months post-transplant. So far, 12 patients (7 men/5 women) with a median age of 55 years (range, 41 to 65 years) have been transplanted. Patients were first assessed and then transplanted a median of 40 and 201 days, respectively, from diagnosis. International Prognostic Index at diagnosis was low (n = 3), low-intermediate (n = 8), and high-intermediate (n = 1). A median of six cycles of CHOP was required to debulk tumor sufficiently for transplant. Response to CHOP was 100% with six complete responses, one complete response unconfirmed, and five partial responses. Transplantation was well tolerated. Patients engrafted quickly, with a median of 11.5 days to neutrophil engraftment and 10 days to platelet independence. Patients had modest transfusion requirements, requiring a median of four units of packed red blood cells and two and a half platelet transfusions. Six to 8 weeks post-transplant, six patients were in complete response, four in complete response unconfirmed, and two in partial response. Eight patients have received all eight maintenance rituximab treatments, and four have received only their first cycle. Following rituximab, the two patients in partial response and two in complete response unconfirmed converted to complete response. With a median follow-up of 239 days from transplant (range, 61 to 727 days), all patients remain alive and well with no documented relapses. Samples for molecular monitoring have been drawn from the stem-cell graft, and serially from the peripheral blood and bone marrow of patients at baseline, preapheresis, pretransplant, and post-transplant at 3-month intervals. This data shows that ASCT followed by rituximab immunotherapy is feasible and safe in patients with MCL. Although patient numbers are low and follow-up time is short, preliminary results are encouraging. Rituximab may convert partial responders to complete responders. The durability of responses will be determined with longer follow-up.
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Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfoma de Célula do Manto/terapia , Adulto , Idoso , Anticorpos Monoclonais Murinos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 14 , Ensaios Clínicos como Assunto , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Genes bcl-1 , Humanos , Imunoterapia/métodos , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prednisona/administração & dosagem , Indução de Remissão , Rituximab , Translocação Genética , Condicionamento Pré-Transplante , Transplante Autólogo , Vincristina/administração & dosagemRESUMO
Patients with relapsed or refractory lymphoma often require treatment with aggressive chemotherapy. At McGill University, a combination of high dose VP-16 and cyclophosphamide (VP-CY) is commonly used as a salvage regimen. In recent years, cytogenetic abnormalities of the long arm of chromosome 11 at band 23 (11q23) have been linked to the use of VP-16, and may be associated with secondary myelodysplastic syndrome or acute leukemia. Therapy related 11q23 anomalies have not been widely studied in lymphoma patients. We have identified and reviewed the course of 107 patients who have been treated with VP-CY. Thirty-five patients remain alive and 21 consented to participate in our study. Patient bone marrows were studied morphologically, cytogenetically and molecularly, to identify any new changes that may have developed over the course of their treatment, with a special emphasis on the search for 11q23 rearrangements. Mean time between VP-CY treatment and marrow evaluation was 3.6 years. Of the 21 patients, 5 had Hodgkin's disease (HD) and 16 had non Hodgkin's lymphoma (NHL). They received a total of 30 cycles of VP-CY. Response rate was 100%, with 16 complete and 5 partial responses. Eighteen patients later underwent autologous stem cell transplantation. At the time of study, 19 of the patients were disease free and 2 were in relapse. On morphological analysis, 12 marrows appeared normal and 6 showed mild dyserythropoiesis. Standard cytogenetics was done to examine for any new chromosomal translocations or deletions. All cytogenetic studies yielded normal results. Molecular analysis by Southern blot was done on 15 patients in a search for 11q23 rearrangements, including the partial tandem duplication of ALL-1. All molecular studies were normal. We conclude that the use of VP-CY, given in our treatment schedule, does not appear to be associated with an increased risk of developing 11q23 rearrangements.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cromossomos Humanos Par 11 , Rearranjo Gênico , Linfoma/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Southern Blotting , Medula Óssea/patologia , Mapeamento Cromossômico , Ciclofosfamida/administração & dosagem , DNA de Neoplasias/genética , DNA de Neoplasias/isolamento & purificação , Etoposídeo/administração & dosagem , Éxons , Feminino , Humanos , Linfoma/genética , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
Desmopressin (DDAVP) is commonly used in the treatment of patients with type 1 von Willebrand disease (VWD) and mild hemophilia A. A patient's responsiveness to DDAVP based on a 0.3 âµg/kg dose determines future therapeutic efficacy of the drug. The aim of the study was to determine whether a capped dose of 15 µg subcutaneous DDAVP is able to achieve the same level of DDAVP responsiveness as previously reported. This is a retrospective chart review of patients from 1995 to 2013 in adults and children with type 1 VWD and hemophilia A weighing more than 50 kg. Levels of factor VIII, ristocetin cofactor, and von Willebrand factor antigen were measured before and after 1 h of administration of 15 µg of DDAVP. In patients with type 1 VWD, the complete response rate was 82.5% with a partial response rate of 12.5% and 5% nonresponders. In patients with mild hemophilia A, the complete response rate was 53.8% with a partial response rate of 38.5% and 7.7% nonresponders. These results using a capped 15-µg dose of DDAVP are similar to previously published reports using the 0.3-µg/kg dose.
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Desamino Arginina Vasopressina/administração & dosagem , Hemofilia A/tratamento farmacológico , Hemostáticos/administração & dosagem , Doença de von Willebrand Tipo 1/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Monitoramento de Medicamentos , Fator VIII/metabolismo , Feminino , Hemofilia A/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Doença de von Willebrand Tipo 1/sangue , Fator de von Willebrand/metabolismoAssuntos
Doença de Gaucher/diagnóstico , Programas de Rastreamento/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá , Hematologia , Humanos , Itália , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Esplenomegalia/complicações , Esplenomegalia/diagnóstico , Centros de Atenção Terciária , Trombocitopenia/complicações , Trombocitopenia/diagnóstico , Adulto JovemRESUMO
Radioimmunotherapy offers a unique treatment modality for indolent non-Hodgkin lymphoma (iNHL). We report 5-year outcomes and quality of life (QoL) in tositumomab and iodine(131)-tositumomab (TST/I(131)-TST) treated patients with iNHL previously treated with rituximab. Ninety-three patients with ≥ 2 lines of therapy, responding to last treatment, were enrolled at 12 Canadian centers. Median age, disease duration and number of prior therapies (#PTx) were 59 years, 4.9 years and 5, respectively. Outcomes were response rate (43.0%), median progression-free survival (mPFS) (12.0 months), 5-year PFS (27%) and median overall survival (OS) (59.8 months). In responders, median response duration and mPFS were not reached. Improvements in QoL were seen by week 7. In univariate and multivariate analyses, hemoglobin, disease bulk and body surface area (BSA) predicted OS, whereas lactate dehydrogenase (LDH), bulk, BSA and #PTx predicted PFS. Most common adverse events (AEs) were fatigue and nausea. Two cases of myelodysplastic syndrome (MDS) were reported. TST/I(131)-TST was associated with durable responses, and prolonged OS and PFS in heavily pretreated iNHL.
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Anticorpos Monoclonais/uso terapêutico , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Radioimunoterapia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Canadá , Feminino , Humanos , Linfoma não Hodgkin/diagnóstico , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Retratamento , Rituximab , Resultado do Tratamento , Carga TumoralRESUMO
Extramedullary relapse of acute lymphoblastic leukemia (ALL) is rare and has been primarily reported in pediatric patients or hematopoietic stem cell transplant recipients. We report a case of a 62-year-old woman who presented with relapsed ALL involving her kidneys, pancreas, and bone marrow 2 years after completing chemotherapy with a standard ALL protocol. Unfortunately, her extramedullary disease progressed despite treatment. To the best of our knowledge, this is the first reported case of extramedullary relapse of B-cell ALL to the kidneys and pancreas occurring in an adult patient who had not previously undergone a hematopoietic stem cell transplant. A literature review of kidney and pancreatic extramedullary relapse in ALL is also included.
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Although patients with Hodgkin lymphoma treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy frequently develop neutropenia, febrile neutropenia is uncommon. Three retrospective trials reported that ABVD could be safely administered without dose delays or granulocyte-colony stimulating factor (G-CSF) support. We retrospectively reviewed the charts of 89 patients treated with ABVD and found that the incidence of febrile neutropenia was 0.5% (five of 927 treatments). This prompted a change to our institutional policy so that patients receiving ABVD no longer receive routine G-CSF for uncomplicated neutropenia. We then prospectively assessed the safety of this policy change. Thirty-three patients received a total of 327 ABVD treatments, 185 (57%) of which were administered with a neutrophil count <1.5 × 10(9)/L. Febrile neutropenia occurred in 2/33 patients (6%), complicating 0.6% of chemotherapy treatments (2/327). Eliminating routine G-CSF saved $10 241 per patient. Omission of G-CSF for uncomplicated neutropenic patients receiving ABVD for Hodgkin lymphoma is cost-saving and safe.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Análise Custo-Benefício , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Febre/induzido quimicamente , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Doença de Hodgkin/economia , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Adulto JovemRESUMO
The addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL). However, combined therapy is associated with increased neurotoxicity. In an effort to limit this toxicity, we treated a series of non-immunocompromised patients with HDMVP, a HD-MTX based regimen, with deferral of WBRT until progression. Twenty-three patients were treated with the HDMVP regimen consisting of MTX, vincristine, and procarbazine. The mean age at diagnosis was 60.9 years (range 45-79 years). The overall response rate was 65% (14 complete responses and one partial response). For patients achieving an initial response with HDMVP the median response duration was 40.4 months (95% confidence interval [CI] 19.5-61.3). The median progression-free survival was 4.6 months (95% CI 0.0-20.4) and median overall survival was 41.4 months (95% CI 0.0-95.5). Fourteen patients received WBRT for relapsed or progressive disease. The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control. Ultimately the majority of the patients in this series required WBRT for salvage treatment, potentially enabling a delay in treatment-associated neurotoxicity.
Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Metotrexato/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/radioterapia , Terapia Combinada/efeitos adversos , Terapia Combinada/mortalidade , Irradiação Craniana , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Procarbazina/uso terapêutico , Indução de Remissão , Taxa de Sobrevida , Vincristina/uso terapêuticoRESUMO
BACKGROUND: Mediastinal radiation can accelerate atherosclerosis in Hodgkin lymphoma survivors (HLS), and early detection is optimal. Peripheral arterial tonometry (PAT), a non-invasive measure of endothelial function, is a surrogate marker of sub-clinical atherosclerosis. The objective of our study was to evaluate endothelial function in HLS and controls using PAT and to determine the influence of mediastinal radiation. PROCEDURE: Cross-sectional evaluation was performed on 26 HLS aged 12-30 years who were a minimum of 2 years from therapy, and their healthy age and gender matched controls. Evaluation included assessment for cardiovascular risk factors and completion of the Habitual Activity Estimation Score (HAES) questionnaire to assess activity level. Endothelial Function was measured using PAT hyperemia ratios (PAT-HR). RESULTS: HLS and controls were similar for baseline variables (mean age 23.3 +/- 5 yrs vs. 23.4 +/- 4.8 yrs, p = 0.92). HLS were on average 6.7 +/- 4.6 yrs post treatment. No differences in endothelial function or cardiovascular risk factors were observed between HLS and controls. However, impaired endothelial function, as evidenced by lower PAT-HR (1.67 +/- 0.39 vs. 2.03 +/- 0.37, p < 0.01) was seen in HLS (n = 13) who received mediastinal radiation (mean radiation dose 2,600 +/- 840 cGy) compared to controls. CONCLUSIONS: Impaired endothelial function was preferentially observed in HLS who received mediastinal radiation, while no difference was observed between the HLS and control groups overall. This finding, assessed using a non invasive test of endothelial function, confirms that mediastinal radiation is an additional cardiovascular risk factor in this young cohort of patients. Further studies of endothelial function in this patient population are warranted.
Assuntos
Endotélio Vascular/fisiopatologia , Doença de Hodgkin/radioterapia , Neoplasias do Mediastino/radioterapia , Sobreviventes , Doenças Vasculares/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Doença de Hodgkin/patologia , Humanos , Masculino , Neoplasias do Mediastino/patologia , Projetos Piloto , Tolerância a Radiação , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Patients with mantle cell lymphoma (MCL) have a particularly poor prognosis when treated with standard chemotherapy, with a median overall survival of only 3 years. These patients have therefore been considered for first-line treatment with more aggressive or experimental strategies, such as high-dose therapy (HDT) with autologous stem cell transplantation (ASCT). While high rates of clinical remission have been achieved with HDT/ASCT, this procedure alone is not believed to be curative and different treatment strategies are being developed to improve outcomes in this group of patients. Single-agent rituximab is active in both newly diagnosed and relapsed MCL and therefore the addition of rituximab to chemotherapy regimens and/or HDT/ASCT may enhance their efficacy. Outside the transplantation setting, rituximab plus chemotherapy has been shown to be highly active in MCL, and preliminary data from randomized trials suggest that the combination may yield superior results compared with chemotherapy alone. The addition of rituximab to transplantation protocols appears to be a very promising strategy for patients with MCL, given as an in vivo purge before HDT/ASCT and/or as posttransplant maintenance therapy. Two phase II clinical trials with rituximab given as an in vivo purge during stem cell mobilization and as posttransplant immunotherapy in patients with previously untreated MCL have generated very promising data. Rituximab is an important addition to cytotoxic therapy and with HDT/ASCT represents a highly active therapy that may be superior to conventional treatment or HDT/ASCT alone in MCL. Randomized prospective studies and longer follow-up are needed to determine whether these regimens can achieve longer survival or possibly cure in this disease.