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3.
Transplant Cell Ther ; 28(8): 487.e1-487.e7, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35609865

RESUMO

Data for outcomes after autologous hematopoietic cell transplantation (auto-HCT) in diffuse large B-cell lymphoma (DLBCL) patients ≥70 years are limited. Auto-HCT is feasible in older DLBCL patients. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes of auto-HCT in DLBCL patients aged 60 to 69 years (n = 363) versus ≥70 years (n = 103) between 2008 and 2019. Non-relapse mortality (NRM), relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models. All patients received BEAM conditioning (carmustine, etoposide, cytosine arabinoside and melphalan). On univariate analysis, in the 60 to 69 years versus ≥70 years cohorts, 100-day NRM was 3% versus 4%, 5-year REL was 47% versus 45%, 5-year PFS 40% versus 38% and 5-year OS 55% versus 41%, respectively. On multivariate analysis, patients ≥70 had no significant difference in NRM (hazard ratio [HR] 1.43, 95% confidence interval [CI] 0.85-2.39), REL (HR 1.11, 95% CI 0.79-1.56), PFS (HR 1.23, 95% CI 0.92-1.63) compared to patients 60 to 69 years. Patients ≥70 years had a higher mortality (HR 1.39, 95% CI 1.05-1.85, p=0.02), likely because of inferior post-relapse OS in this cohort (HR 1.82, 95% CI 1.27-2.61, P = .001). DLBCL was the major cause of death in both cohorts (62% versus 59%). Older patients should not be denied auto-HCT solely on the basis of chronological age.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Idoso , Humanos , Linfoma Difuso de Grandes Células B/terapia , Recidiva Local de Neoplasia , Condicionamento Pré-Transplante , Transplante Autólogo
4.
Br J Haematol ; 195(5): 757-763, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34581433

RESUMO

In young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front-line setting. Recently, time-to-event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post-autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six-month [hazard ratio (HR) = 7·68], 12-month (HR = 6·68), and 18-month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non-relapsing patients. Furthermore, early relapse (<18 months) following autoHCT defines a high-risk group with inferior post-relapse OS. This retrospective analysis highlights the impact of time to relapse on OS in MCL patients undergoing up-front autoHCT and emphasizes the need to consider novel therapeutic approaches for patients suffering early relapse.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Célula do Manto/terapia , Adulto , Idoso , Feminino , Humanos , Linfoma de Célula do Manto/diagnóstico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Transplante Autólogo
5.
Transpl Infect Dis ; 23(4): e13689, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34255395

RESUMO

BACKGROUND: Autologous hematopoietic stem cell transplantation (HSCT) recipients are at increased risk of developing life-threatening infections. There is discordance in published recommendations for timing of pre- and post-transplant antimicrobial prophylaxis in this patient population, and these recommendations are unsubstantiated by any published comparative analyses. METHODS: An observational, pre- and post-intervention study of consecutive autologous HSCT recipients was conducted over a 2-year period. In the pre-intervention cohort, antimicrobial prophylaxis was initiated on the day prior to transplant. In the post-intervention cohort, antimicrobials were initiated once absolute neutrophil count (ANC) reached ≤500 cells/mm3 . The primary outcome assessed was frequency of febrile occurrences. Secondary outcomes included total days of prophylaxis, positive blood cultures, all-cause mortality, Clostridioides difficile infection rates, and length of stay. RESULTS: A total of 208 patients were included in the final analysis, with 105 and 103 patients in the pre- and post-intervention cohorts, respectively. The majority of patients included were male. Lower rates of fever occurrences were observed in the post-intervention cohort (83% pre- vs. 69% post-intervention; p = 0.019). A significant reduction in the mean antibacterial days per patient was identified (9.7 vs. 4.6 days; p < 0.001). Other than lower rates of febrile neutropenia in the post-intervention cohort, no differences were identified in secondary outcomes. In multivariable analyses, ANC-driven prophylaxis was independently associated with decreased febrile events. CONCLUSIONS: Delaying prophylaxis until severe neutropenia was not associated with increased febrile events or other secondary clinical outcomes evaluated. This approach is associated with a significant reduction in antimicrobial exposure.


Assuntos
Anti-Infecciosos , Transplante de Células-Tronco Hematopoéticas , Antibacterianos/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Neutrófilos , Estudos Retrospectivos , Transplantados
6.
Transpl Infect Dis ; 21(5): e13145, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31301099

RESUMO

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are associated with significant morbidity and mortality following allogeneic hematopoietic cell transplant (alloHCT). Although most PTLD is EBV-positive (EBVpos ), EBV-negative (EBVneg ) PTLD is reported, yet its incidence and clinical impact remain largely undefined. Furthermore, factors at the time of transplant impacting survival following PTLD are not well described. METHODS: Between 2002 and 2014, 432 cases of PTLD following alloHCT were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). After exclusions, 267 cases (EBVpos  = 222, 83%; EBVneg  = 45, 17%) were analyzed. RESULTS: Two hundred and eight patients (78%) received in vivo T-cell depletion (TCD) with either anti-thymocyte globulin (ATG) or alemtuzumab. Incidence of PTLD was highest using umbilical cord donors (UCB, 1.60%) and lowest using matched related donors (MRD, 0.40%). Clinical features and histology did not significantly differ among EBVpos or EBVneg PTLD cases except that absolute lymphocyte count recovery was slower, and CMV reactivation was later in EBVneg PTLD [EBVpos 32 (5-95) days versus EBVneg 47 (10-70) days, P = .016]. There was no impact on survival by EBV status in multivariable analysis [EBVneg RR 1.42, 95% CI 0.94-2.15, P = .097]. CONCLUSIONS: There is no difference in survival outcomes for patients with EBVpos or EBVneg PTLD occurring following alloHCT and 1-year survival is poor. Features of conditioning and use of serotherapy remain important.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Herpesvirus Humano 4/genética , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Carga Viral , Adulto Jovem
7.
Biol Blood Marrow Transplant ; 25(11): 2160-2166, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31279752

RESUMO

We set out to assess feasibility and safety of allogeneic hematopoietic cell transplant in 17 persons with HIV in a phase II prospective multicenter trial. The primary endpoint was 100-day nonrelapse mortality (NRM). Patients had an 8/8 HLA-matched related or at least a 7/8 HLA-matched unrelated donor. Indications for transplant were acute leukemia, myelodysplasia, and lymphoma. Conditioning was myeloablative or reduced intensity. There was no NRM at 100 days. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 41%. At 1 year, overall survival was 59%; deaths were from relapsed/progressive disease (n = 5), acute GVHD (n = 1), adult respiratory distress syndrome (n = 1), and liver failure (n = 1). In patients who achieved complete chimerism, cell-associated HIV DNA and inducible infectious virus in the blood were not detectable. Blood and Marrow Transplant Clinical Trials Network 0903/AIDS Malignancy Consortium 080 was registered at www.clinicaltrials.gov (no. NCT01410344).


Assuntos
Infecções por HIV/terapia , HIV-1 , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Adulto , Aloenxertos , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Infecções por HIV/sangue , Infecções por HIV/mortalidade , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/prevenção & controle
8.
Haematologica ; 104(4): 844-854, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30381298

RESUMO

Unlike unrelated donor registries, transplant centers lack uniform approaches to related donor assessment and deferral. To test whether related donors are at increased risk for donation-related toxicities, we conducted a prospective observational trial of 11,942 related and unrelated donors aged 18-60 years. Bone marrow (BM) was collected at 37 transplant and 78 National Marrow Donor Program centers, and peripheral blood stem cells (PBSC) were collected at 42 transplant and 87 unrelated donor centers in North America. Possible presence of medical comorbidities was verified prior to donation, and standardized pain and toxicity measures were assessed pre-donation, peri-donation, and one year following. Multivariate analyses showed similar experiences for BM collection in related and unrelated donors; however, related stem cell donors had increased risk of moderate [odds ratios (ORs) 1.42; P<0.001] and severe (OR 8.91; P<0.001) pain and toxicities (OR 1.84; P<0.001) with collection. Related stem cell donors were at increased risk of persistent toxicities (OR 1.56; P=0.021) and non-recovery from pain (OR 1.42; P=0.001) at one year. Related donors with more significant comorbidities were at especially high risk for grade 2-4 pain (OR 3.43; P<0.001) and non-recovery from toxicities (OR 3.71; P<0.001) at one year. Related donors with more significant comorbidities were at especially high risk for grade 2-4 pain (OR 3.43; P<0.001) and non-recovery from toxicities (OR 3.71; P<0.001) at one year. Related donors reporting grade ≥2 pain had significant decreases in Health-Related Quality of Life (HR-QoL) scores at one month and one year post donation (P=0.004). In conclusion, related PBSC donors with comorbidities are at increased risk for pain, toxicity, and non-recovery at one year after donation. Risk profiles described in this study should be used for donor education, planning studies to improve the related donor experience, and decisions regarding donor deferral. Registered at clinicaltrials.gov identifier:00948636.


Assuntos
Doadores Vivos , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico , Qualidade de Vida , Doadores não Relacionados , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
9.
Biol Blood Marrow Transplant ; 25(4): 699-711, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30423480

RESUMO

The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study. RDs aged > 60 had a lower median CD34+ level before apheresis compared with younger RDs (age > 60, 59 × 106/L; age 41 to 60, 81 × 106/L; age 18 to 40, 121 × 106/L; P < .001). This resulted in older donors undergoing more apheresis procedures (49% versus 30% ≥ 2 collections, P < .001) and higher collection volumes (52% versus 32% > 24 L, P < .001), leading to high percentages of donors aged > 60 with postcollection thrombocytopenia <50 × 109/L (26% and 57% after 2 and 3days of collection, respectively). RDs aged 18 to 40 had a higher risk of grades 2 to 4 pain and symptoms pericollection, but donors over age 40 had more persistent pain at 1, 6, and 12 months (odds ratio [OR], 1.7; P = 0.02) and a higher rate of nonrecovery to predonation levels (OR, 1.7; P = .01). Donors reporting comorbidities increased significantly with age, and those with comorbidities that would have led to deferral by National Marrow Donor Program unrelated donor standards had an increased risk for persistent grades 2 to 4 pain (OR, 2.41; P < .001) and failure to recover to predonation baseline for other symptoms (OR, 2.34; P = .004). This information should be used in counseling RDs regarding risk and can assist in developing practice approaches aimed at improving the RD experience for high-risk individuals.


Assuntos
Transplante de Células-Tronco de Sangue Periférico/métodos , Células-Tronco de Sangue Periférico/metabolismo , Adolescente , Adulto , Idoso , Doadores de Sangue , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Biol Blood Marrow Transplant ; 24(11): 2216-2223, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30006305

RESUMO

We recently conducted a randomized double-blind study in which we demonstrated that moderate/severe chronic graft-versus-host disease (cGVHD) but not cGVHD-free survival was reduced in patients receiving anti-T lymphocyte globulin (ATLG) versus placebo. In a companion study we performed immunophenotypic analysis to determine the impact of ATLG on immune reconstitution (IR) and to correlate IR with clinical outcomes. The randomized study (n = 254) included patients (aged 18 to 65 years) who underwent myeloablative transplants for acute myeloid leukemia, myelodysplastic syndrome, or acute lymphoblastic leukemia from HLA-matched unrelated donors. Ninety-one patients consented for the companion IR study (ATLG = 44, placebo = 47). Blood samples were collected on days 30, 100, 180, and 360 after hematopoietic cell transplantation (HCT), and multiparameter flow cytometry was performed in a blinded fashion. Reconstitution of CD3+ and CD4+ T cells was delayed up to 6 months post-HCT in the ATLG arm, whereas absolute regulatory T cell (Treg) (CD4+25+127-) numbers were lower only in the first 100 days. Analysis of the CD4+ Treg and conventional T cells (Tconv) (CD4+25-127+) compartments showed a profound absence of naive Tregs and Tconv in the first 100 days post-HCT, with very slow recovery for 1 year. B cell and natural killer cell recovery were similar in each arm. Higher absolute counts of CD3+, CD4+, CD8+ T, Tregs, and Tconv were associated with improved overall survival, progression-free survival, and nonrelapse mortality but not moderate/severe cGVHD. Although ATLG delays CD3+ and CD4+ T cell recovery post-transplant, it has a relative Treg sparing effect after the early post-HCT period, with possible implications for protection from cGVHD. ATLG severely compromises the generation of naive CD4+ cells (Treg and Tconv), potentially affecting the diversity of the TCR repertoire and T cell responses against malignancy and infection.


Assuntos
Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/métodos , Reconstituição Imune/imunologia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adolescente , Adulto , Idoso , Soro Antilinfocitário/farmacologia , Método Duplo-Cego , Feminino , Doença Enxerto-Hospedeiro/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Doadores não Relacionados , Adulto Jovem
11.
Biol Blood Marrow Transplant ; 24(6): 1119-1124, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29608957

RESUMO

Significant advances in hematopoietic cell transplantation (HCT) have increased the long-term survivorship of its recipients, but because of unique complications arising from radiation and chemotherapy, recipients require lifelong follow-up. To evaluate current survivorship or long-term follow-up (LTFU) clinics specifically for HCT survivors and to evaluate the potential barriers in their establishment, the American Society for Blood and Marrow Transplantation (ASBMT) Practice Guidelines Committee electronically surveyed 200 HCT programs to gather quantitative and qualitative data about models of care. Among 77 programs (38.5%) that responded, 45% indicated presence of an LTFU clinic; however, LTFU care models varied with respect to services provided, specialist availability, type of patients served, and staffing. Among 55% of programs without an LTFU clinic, 100% agreed that allogeneic HCT survivors have unique needs separate from graft-versus-host disease and that complications could arise during the transition of care either from pediatric to adult settings or away from the HCT center. Lack of expertise, logistics, financial issues, and the observation that 84% of individual practitioners prefer to provide survivorship care were the identified obstacles to establishing new LTFU clinics. The ASBMT hopes that policymakers, HCT providers, and institutions will benefit from the results of this survey and recommends that delivering guidelines-driven screening and expert management of late effects is the goal of first-rate HCT survivorship care.


Assuntos
Atenção à Saúde/organização & administração , Transplante de Células-Tronco Hematopoéticas/métodos , Assistência de Longa Duração/métodos , Sobreviventes , Atenção à Saúde/normas , Seguimentos , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Assistência de Longa Duração/organização & administração , Inquéritos e Questionários , Fatores de Tempo
12.
J Clin Oncol ; 35(36): 4003-4011, 2017 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-29040031

RESUMO

Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days -3, -2, -1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.


Assuntos
Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Doença Enxerto-Hospedeiro/etiologia , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores/uso terapêutico , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Tacrolimo/uso terapêutico , Adulto Jovem
13.
Biol Blood Marrow Transplant ; 22(11): 1915-1925, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27481448

RESUMO

The Practice Guidelines Committee of the American Society of Blood or Marrow Transplantation (ASBMT) sought to develop an evidence-based review about personalizing busulfan-based conditioning. The Committee sought to grade the relevant published studies (June 1, 2008 through March 31, 2016) according to criteria set forth by the Steering Committee for Evidence Based Reviews from ASBMT. Unfortunately, the published literature was too heterogeneous and lacked adequately powered and sufficiently controlled studies for this to be feasible. Despite this observation, the continued interest in this topic led the Practice Guidelines Committee to develop a list of most frequently asked questions (FAQs) regarding personalized busulfan dosing. This "Considerations" document is a list of these FAQs and their responses, addressing topics of practical relevance to hematopoietic cell transplantation clinicians.


Assuntos
Bussulfano/administração & dosagem , Medicina de Precisão/métodos , Condicionamento Pré-Transplante/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Agonistas Mieloablativos/uso terapêutico
14.
Biol Blood Marrow Transplant ; 21(11): 1921-5, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26033279

RESUMO

There are limited data available supporting the use of the recombinant granulocyte colony-stimulating factor (G-CSF), tbo-filgrastim, rather than traditionally used filgrastim to mobilize peripheral blood stem cells (PBSC) or to accelerate engraftment after autologous stem cell transplantation (ASCT). We sought to compare the efficacy and cost of tbo-filgrastim to filgrastim in these settings. Patients diagnosed with lymphoma or plasma cell disorders undergoing G-CSF mobilization, with or without plerixafor, were included in this retrospective analysis. The primary outcome was total collected CD34(+) cells/kg. Secondary mobilization endpoints included peripheral CD34(+) cells/µL on days 4 and 5 of mobilization, adjunctive use of plerixafor, CD34(+) cells/kg collected on day 5, number of collection days and volumes processed, number of collections reaching 5 million CD34(+) cells/kg, and percent reaching target collection goal in 1 day. Secondary engraftment endpoints included time to neutrophil and platelet engraftment, number of blood product transfusions required before engraftment, events of febrile neutropenia, and length of stay. A total of 185 patients were included in the final analysis. Patients receiving filgrastim (n = 86) collected a median of 5.56 × 10(6) CD34(+) cells/kg, compared with a median of 5.85 × 10(6) CD34(+) cells/kg in the tbo-filgrastim group (n = 99; P = .58). There were no statistically significant differences in all secondary endpoints with the exception of apheresis volumes processed (tbo-filgrastim, 17.0 liters versus filgrastim, 19.7 liters; P < .01) and mean platelet transfusions (tbo-filgrastim, 1.7 units versus filgrastim, 1.4 units; P = .04). In conclusion, tbo-filgrastim demonstrated similar CD34(+) yield compared with filgrastim in mobilization and post-transplantation settings, with no clinically meaningful differences in secondary efficacy and safety endpoints. Furthermore, tbo-filgrastim utilization was associated with cost savings of approximately $1406 per patient utilizing average wholesale price.


Assuntos
Filgrastim/farmacologia , Mobilização de Células-Tronco Hematopoéticas/economia , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células B/terapia , Linfoma de Células T/terapia , Mieloma Múltiplo/terapia , Neoplasias de Plasmócitos/terapia , Adulto , Idoso , Antígenos CD34/imunologia , Benzilaminas , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Plaquetas/imunologia , Análise Custo-Benefício , Ciclamos , Feminino , Filgrastim/análogos & derivados , Filgrastim/economia , Sobrevivência de Enxerto , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/uso terapêutico , Humanos , Tempo de Internação/economia , Linfoma de Células B/economia , Linfoma de Células B/imunologia , Linfoma de Células B/patologia , Linfoma de Células T/economia , Linfoma de Células T/imunologia , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/economia , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/patologia , Neoplasias de Plasmócitos/economia , Neoplasias de Plasmócitos/imunologia , Neoplasias de Plasmócitos/patologia , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Estudos Retrospectivos , Transplante Autólogo
15.
Case Rep Hematol ; 2015: 809313, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25922770

RESUMO

The use of high dose chemotherapy followed by autologous hematopoietic stem cell transplantation for remission consolidation after initial induction represents standard of care for patients with multiple myeloma. Patients with myeloma and Acquired von Willebrand Syndrome (AVWS) undergoing autologous stem cell transplant (ASCT) are at significant risk of bleeding due to the profound thrombocytopenia, low Factor VIII levels, fever, and toxicities associated with the preparative regimen. We report a patient with AVWS associated with multiple myeloma who underwent autologous stem cell transplants as consolidation after initial induction and again at relapse. He was successfully treated with high dose intravenous immunoglobulin (IVIG) prior to each transplant with rapid resolution of AVWS.

16.
Biol Blood Marrow Transplant ; 21(7): 1155-66, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25769794

RESUMO

Therapeutic strategies for multiple myeloma (MM) have changed dramatically over the past decade. Thus, the role of hematopoietic stem cell transplantation (HCT) must be considered in the context of this evolution. In this evidence-based review, we have critically analyzed the data from the most recent clinical trials to better understand how to incorporate HCT and when HCT is indicated. We have provided our recommendations based on strength of evidence with the knowledge that ongoing clinical trials make this a dynamic field. Within this document, we discuss the decision to proceed with autologous HCT, factors to consider before proceeding to HCT, the role of tandem autologous HCT, post-HCT maintenance therapy, and the role of allogeneic HCT for patients with MM.


Assuntos
Raios gama/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Agonistas Mieloablativos/uso terapêutico , Condicionamento Pré-Transplante/métodos , Fatores Etários , Aberrações Cromossômicas , Gerenciamento Clínico , Medicina Baseada em Evidências , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Transplante Autólogo , Transplante Homólogo
17.
Biol Blood Marrow Transplant ; 20(12): 1949-57, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25139216

RESUMO

Patients with multiple myeloma (MM) who relapse after autologous transplantation have limited therapeutic options. We conducted a prospective, multicenter, phase IIa study to investigate the safety and efficacy of i.v. busulfan (Bu) in combination with bortezomib as a conditioning regimen for a second autotransplantation. Because a safe Bu exposure was unknown in patients receiving this combination, Bu was initially targeted to a total area under the concentration-time curve (AUC) of 20,000 µM × minute. As no concentration-limiting toxicity was observed in 6 patients, this Bu exposure was utilized in the following treatment cohort (n = 24). Individualized Bu dose, based on test dose .8 mg/kg pharmacokinetics (PK), was administered daily for 4 consecutive days starting 5 days before transplantation, followed by a single dose of bortezomib (1.3 mg/m(2)) 1 day before transplantation. The total mean dose of i.v. Bu (including the test dose and 4-day administration) was 14.2 mg/kg (standard deviation = 2.48; range, 8.7 to 19.2). Confirmatory PK demonstrated that only 2 of 30 patients who underwent transplantation were dosed outside the Bu AUC target and dose adjustments were made for the last 2 doses of i.v. Bu. The median age was 59 years (range, 48 to 73). Median time from first to second transplantation was 28.0 months (range, 12 to 119). Of 26 evaluable patients, 10 patients attained a partial response (PR) or better at 3 months after transplantation, with 2 patients attaining a complete response. At 6 months after transplantation, 5 of 12 evaluable patients had maintained or improved their disease status. Median progression-free survival was 191 days, whereas median overall survival was not reached during the study period. The most common grade 3 and 4 toxicities were febrile neutropenia (50.0%) and stomatitis (43.3%). One transplantation-related death was observed. A combination of dose-targeted i.v. Bu and bortezomib induced PR or better in one third of patients with MM who underwent a second autotransplantation, with acceptable toxicity.


Assuntos
Antineoplásicos , Ácidos Borônicos , Bussulfano , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Agonistas Mieloablativos , Pirazinas , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Autoenxertos , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/efeitos adversos , Ácidos Borônicos/farmacocinética , Bortezomib , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Bussulfano/farmacocinética , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Agonistas Mieloablativos/administração & dosagem , Agonistas Mieloablativos/efeitos adversos , Agonistas Mieloablativos/farmacocinética , Estudos Prospectivos , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Pirazinas/farmacocinética , Taxa de Sobrevida
18.
Biol Blood Marrow Transplant ; 20(9): 1262-73, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24816581

RESUMO

Peripheral blood progenitor cell mobilization practices vary significantly among institutions. Effective mobilization regimens include growth factor alone, chemotherapy and growth factor combined, and, more recently, incorporation of plerixafor with either approach. Many institutions have developed algorithms to improve stem cell mobilization success rates and cost-effectiveness. However, an optimal stem cell mobilization regimen has not been defined. Practical guidelines are needed to address important clinical questions, including which growth factor is optimal, what chemotherapy and dose is most effective, and when to initiate leukapheresis. We present recommendations, based on a comprehensive review of the literature, from the American Society of Blood and Marrow Transplantation.


Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco/metabolismo , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Transplante Homólogo/métodos , Guias como Assunto , Humanos , Estados Unidos
19.
Biol Blood Marrow Transplant ; 20(5): 600-16, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24462742

RESUMO

Hematopoietic stem cell transplantation (HCT) is a potentially life-saving therapy for patients with malignant and nonmalignant disease states. This article reviews the current published literature on the dosing of pharmacologic agents used for HCT preparative regimens with specific focus on the obese patient population. The review found that dose adjustments for obesity have, to date, been based empirically or extrapolated from published data in the nontransplantation patient population. As a result, the Committee determined that clear standards or dosing guidelines are unable to be made for the obese population because Level I and II evidence are unavailable at this time. Instead, the Committee provides a current published literature review to serve as a platform for conditioning agent dose selection in the setting of obesity. A necessary goal should be to encourage future prospective trials in this patient population because further information is needed to enhance our knowledge of the pharmacokinetics and pharmacodynamics of conditioning agents in the setting of obesity.


Assuntos
Transplante de Medula Óssea , Doenças Hematológicas , Transplante de Células-Tronco Hematopoéticas , Agonistas Mieloablativos , Obesidade , Condicionamento Pré-Transplante , Humanos , Soro Antilinfocitário/uso terapêutico , Bussulfano/uso terapêutico , Ciclofosfamida/uso terapêutico , Citarabina/uso terapêutico , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Etoposídeo/uso terapêutico , Doenças Hematológicas/complicações , Doenças Hematológicas/patologia , Doenças Hematológicas/terapia , Melfalan/uso terapêutico , Agonistas Mieloablativos/uso terapêutico , Obesidade/complicações , Obesidade/patologia , Obesidade/terapia
20.
Biol Blood Marrow Transplant ; 20(3): 295-308, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24141007

RESUMO

Autologous hematopoietic stem cell transplantation (aHSCT) is a well-established treatment for malignancies such as multiple myeloma (MM) and lymphomas. Various changes in the field over the past decade, including the frequent use of tandem aHSCT in MM, the advent of novel therapies for the treatment of MM and lymphoma, and the addition of new stem cell mobilization techniques, have led to the need to reassess current stem cell mobilization strategies. Mobilization failures with traditional strategies are common and result in delays in treatment and increased cost and resource utilization. Recently, plerixafor-containing strategies have been shown to significantly reduce mobilization failure rates, but the ideal method to maximize stem cell yields and minimize costs associated with collection has not yet been determined. A panel of experts convened to discuss the currently available data on autologous hematopoietic stem cell mobilization and transplantation and to devise guidelines to optimize mobilization strategies. Herein is a summary of their discussion and consensus.


Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas , Compostos Heterocíclicos/uso terapêutico , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Benzilaminas , Ciclamos , Filgrastim , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/normas , Doença de Hodgkin/imunologia , Doença de Hodgkin/mortalidade , Humanos , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/mortalidade , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/mortalidade , Polietilenoglicóis , Proteínas Recombinantes/uso terapêutico , Análise de Sobrevida , Transplante Autólogo
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