RESUMO
Systemic amyloidosis is a rare protein misfolding and deposition disorder leading to progressive organ failure. There are over 15 types of systemic amyloidosis, each caused by a different precursor protein which promotes amyloid formation and tissue deposition. Amyloidosis can be acquired or hereditary and can affect various organs, including the heart, kidneys, liver, nerves, gastrointestinal tract, lungs, muscles, skin and soft tissues. Symptoms are usually insidious and nonspecific resulting in diagnostic delay. The field of amyloidosis has seen significant improvements over the past decade in diagnostic accuracy, prognosis prediction and management. The advent of mass spectrometry-based shotgun proteomics has revolutionized amyloid typing and has led to the discovery of new amyloid types. Accurate typing of the precursor protein is of paramount importance as the type dictates a specific management approach. In this article, we review each type of systemic amyloidosis to provide the practitioner with practical tools to improve diagnosis and management of these rare disorders.
Assuntos
Amiloidose/diagnóstico , Amiloidose/terapia , Proteômica/métodos , Amiloidose/classificação , Biomarcadores/análise , Diagnóstico por Imagem , Progressão da Doença , Humanos , Espectrometria de Massas , PrognósticoRESUMO
BACKGROUND: Data on the effect of systemic immunoglobulin light chain amyloidosis (AL amyloidosis) on thyroid function are limited. OBJECTIVE: To assess the prevalence of hypothyroidism in AL amyloidosis patients and determine its predictors. METHODS: 1142 newly diagnosed AL amyloidosis patients were grouped based on the thyroid-stimulating hormone (TSH) measurement at diagnosis: hypothyroid group (TSH above upper normal reference; >5 mIU L-1 ; n = 217, 19% of study participants) and euthyroid group (n = 925, 81%). Predictors for hypothyroidism were assessed in a binary multivariate model. Survival between groups was compared using the log-rank test and a multivariate analysis. RESULTS: Patients with hypothyroidism were older, more likely to present with renal and hepatic involvement and had a higher light chain burden compared to patients in the euthyroid group. Higher proteinuria in patients with renal involvement and lower albumin in patients with hepatic involvement were associated with hypothyroidism. In a binary logistic regression model, age ≥65 years, female sex, renal involvement, hepatic involvement, kappa light chain restriction and amiodarone use were independently associated with hypothyroidism. Ninety-three per cent of patients in the hypothyroid group with free thyroxine measurement had normal values, consistent with subclinical hypothyroidism. Patients in the hypothyroid group had a shorter survival compared to patients in the euthyroid group (4-year survival 36% vs 43%; P = 0.008), a difference that was maintained in a multivariate analysis. CONCLUSION: A significant proportion of patients with AL amyloidosis present with hypothyroidism, predominantly subclinical, which carries a survival disadvantage. Routine assessment of TSH in these patients is warranted.
Assuntos
Amiloidose/epidemiologia , Hipotireoidismo/epidemiologia , Idoso , Amiloidose/mortalidade , Anticorpos/sangue , Comorbidade , Feminino , Terapia de Reposição Hormonal , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/etiologia , Iodeto Peroxidase/imunologia , Nefropatias/epidemiologia , Hepatopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Sobrevida , Hormônios Tireóideos/uso terapêutico , Tireotropina/sangue , Tiroxina/sangueRESUMO
Inherited forms of amyloidosis are rare; of these, transthyretin-related (ATTR) is the most common, but non-ATTR has been described as well. We studied a large case series of ATTR and a small series of non-ATTR to better determine the mutation frequencies and geographic distributions of these inherited forms of amyloidosis in the United States. We performed a retrospective cross-sectional study of 284 ATTR and non-ATTR patients seen at Mayo Clinic in Rochester, Minnesota, from 1 January 1970 through 29 January 2013. Mutations were identified by DNA sequencing, restriction fragment length polymorphism, or mass spectroscopy. The genetic testing method was unknown for several patients, but a small proportion were identified by family history or by classical clinical presentation associated with a specific mutation. The most common ATTR mutations were Thr60Ala (24%), Val30Met (15%), Val122Ile (10%), and Ser77Tyr (5%). Non-ATTR mutations included gelsolin (n = 3), apolipoprotein A-I (n = 6), apolipoprotein A-II (n = 1), fibrinogen A-α (n = 9), and lysozyme (n = 1). Although rare, ATTR and, to a lesser extent, non-ATTR are prevalent in the United States and should be considered for patients presenting in the appropriate clinical context.
Assuntos
Neuropatias Amiloides Familiares/genética , Predisposição Genética para Doença/epidemiologia , Pré-Albumina/genética , Análise Mutacional de DNA , Feminino , Testes Genéticos , Geografia , Humanos , Masculino , Mutação de Sentido Incorreto , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Belantamab mafodotin is a highly selective targeted therapy for multiple myeloma. It targets the B cell maturation antigen (BCMA) on plasma cells and showed promising results in several randomized clinical trials. We report the outcomes of 36 patients treated at Mayo Clinic. Our cohort received a median of eight prior lines of therapy. Six patients received belantamab in combination with other medications (pomalidomide, cyclophosphamide, thalidomide), 13 patients (36%) were 70 years or older, two patients had a creatinine of >2.5 mg/dL, and one patient was on dialysis. All three patients with renal failure received full dose belantamab. Chimeric antigen receptor (CAR-T) therapy was used prior to belantamab in seven patients and none of them responded to belantamab therapy. The overall response rate (ORR) was 33% (CR 6%, VGPR 8%, PR 19%), like the ORR reported in the DREAMM-2 trial. Keratopathy developed in 16 patients (43%), grade 1 in six patients, grade 2 in seven patients, and grade 3 in three patients. Eight percent discontinued therapy due to keratopathy. The median PFS and OS was 2 months and 6.5 months, respectively.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Following the publication of this article the authors noted that the MRD data under the Table 1 column "Remark" of Aspire should go to that of Pollux. The authors wish to apologize for any inconvenience caused. The corrected table is attached to this correction.
RESUMO
Cast nephropathy is the most common cause of renal disease in multiple myeloma, however, treatment with plasma exchange remains controversial even after 3 randomized controlled studies. We sought to determine the importance of diagnostic confirmation and goal directed therapy in the treatment of cast nephropathy in forty patients with confirmed multiple myeloma and renal failure who underwent plasma exchange. A positive renal response was defined as a decrease by half in the presenting serum creatinine and dialysis independence. No baseline differences were noted between eventual renal responders and non-responders. Three quarters of the patients with biopsy proven cast nephropathy resolved their renal disease when the free light chains present in the serum were reduced by half or more but there was no significant response when the reduction was less. The median time to a response was about 2 months. In patients without cast nephropathy, renal recovery occurred despite reductions in free light chain levels of the serum. No association was found between free light chains in the serum, urinary monoclonal proteins, overall proteinuria and cast nephropathy. We found that the relationship between renal recovery and free light chain reduction was present only in patients with biopsy proven cast nephropathy showing the importance of extracorporeal light chain removal in this disease.
Assuntos
Cadeias Leves de Imunoglobulina/sangue , Neoplasias Renais/complicações , Mieloma Múltiplo/complicações , Troca Plasmática , Insuficiência Renal/diagnóstico , Insuficiência Renal/terapia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/urina , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Insuficiência Renal/etiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Autologous SCT (ASCT) remains an effective therapy for eligible patients with myeloma. Previous studies have suggested a lack of impact of the initial therapy on the outcome after ASCT. It is not clear if incorporation of new agents in the initial treatment regimens will have any impact on the outcome after ASCT. We studied 472 patients undergoing ASCT within 12 months of diagnosis to assess the effect of initial therapy on the outcome after ASCT. Patients received initial therapy with vincristine, adriamycin and dexamethasone (VAD), dexamethasone, thalidomide and dexamethasone or lenalidomide and dexamethasone. While patients treated with dexamethasone alone had higher disease burden at ASCT, no differences were observed in the response rates to ASCT, post transplant complications or treatment-related mortality among the groups. The median time to progression after ASCT was 27.1, 24.7, 21.1 months and did not reach the VAD, Dex, Thal-Dex and Len-Dex group, respectively, P=0.11. The median overall survival from ASCT was 62 months for VAD, 69.6 months for Dex and were not reached for Thal-Dex and Len-Dex groups, P=0.2. For patients undergoing early ASCT for myeloma, the nature of initial treatment utilized has no long-term impact on the outcome of ASCT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adulto , Idoso , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Lenalidomida , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Estudos Retrospectivos , Talidomida/administração & dosagem , Talidomida/análogos & derivados , Condicionamento Pré-Transplante/métodos , Transplante AutólogoRESUMO
While initial therapies have become highly effective with introduction of lenalidomide and bortezomib and patients may opt for delayed stem cell transplantation, it is important to collect stem cells for future transplant. Given its increasing use as initial therapy, we examined if lenalidomide had any impact on the ability to collect peripheral blood stem cells (PBSC). We studied the entire cohort of patients with myeloma undergoing PBSC mobilization at our institution during a 5-year period, comparing the results between patients receiving different initial therapies. Among those mobilized with granulocyte-colony stimulating factor (G-CSF) alone, there was a significant decrease in total CD34(+) cells collected (P<0.001), average daily collection (P<0.001), day 1 collection (P<0.001) and increased number of aphereses (P=0.004) in patients treated with lenalidomide compared to those receiving dexamethasone, thalidomide-dexamethasone or VAD. A similar trend was seen in those mobilized with chemotherapy and G-CSF. A trend was seen towards decreased PBSC yield with increasing duration of lenalidomide therapy as well as increasing age (P=0.002). There was no effect on quality of PBSC collected based on similar engraftment across all groups. We recommend collection of PBSC within 6 months of initiation of therapy with lenalidomide containing regimens to minimize the risk of mobilization failures.
Assuntos
Antineoplásicos/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Adulto , Idoso , Inibidores da Angiogênese/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Combinada , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Talidomida/administração & dosagem , Talidomida/farmacologia , Vincristina/administração & dosagemRESUMO
Clinical outcomes for multiple myeloma (MM) are highly heterogeneous and it is now clear that pivotal genetic events are the primary harbingers of such variation. These findings have broad implications for counseling, choice of therapy and the design and interpretation of clinical investigation. Indeed, as in acute leukemias and non-hodgkins lymphoma, we believe it is no longer acceptable to consider MM a single disease entity. As such, the accurate diagnosis of MM subtypes and the adoption of common criteria for the identification and stratification of MM patients has become critical. Herein, we provide a consensus high-risk definition and offer practical guidelines for the adoption of routine diagnostic testing. Although acknowledging that more refined classifications will continue to be developed, we propose that the definition of high-risk disease (any of the t(4;14), t(14;16), t(14;20), deletion 17q13, aneuploidy or deletion chromosome 13 by metaphase cytogenetics, or plasma cell labeling index >3.0) be adopted. This classification will identify most of the 25% of MM patients for whom current therapies are inadequate and for whom investigational regimens should be vigorously pursued. Conversely, the 75% of patients remaining have more favorable outcomes using existing - albeit non-curative - therapeutic options.
Assuntos
Ensaios Clínicos como Assunto/normas , Mieloma Múltiplo/classificação , Antineoplásicos/uso terapêutico , Cromossomos Humanos/genética , Cromossomos Humanos/ultraestrutura , Aconselhamento , Tomada de Decisões , Testes Diagnósticos de Rotina , Desenho de Fármacos , Marcação de Genes , Terapia Genética , Genótipo , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Plasmócitos/patologia , Prognóstico , Risco , Medição de Risco , Translocação Genética , Resultado do Tratamento , Carga TumoralRESUMO
The significance of elevated C-reactive protein (CRP) prior to autologous stem cell transplantation (ASCT) in multiple myeloma (MM) has not been studied. We analyzed 1111 MM patients who underwent ASCT at Mayo Clinic from 2007 to 2015. A total of 840 patients (76%) received early ASCT (⩽12 months from diagnosis) and 271 patients (24%) received delayed ASCT (>12 months from diagnosis). Elevated CRP (> upper normal limit (8 mg/L)) was seen in 14% and 22% of patients undergoing early and delayed ASCT, respectively (P=0.003). There was no correlation of CRP with pre-transplant response, bone marrow plasma cell percentage or labeling index. Patients with an elevated CRP had a higher likelihood of having circulating plasma cells prior to ASCT (33 vs 19%; P<0.001). In the early ASCT cohort, the median overall survival (OS) in patients with normal and elevated CRP was not reached and 91 months respectively (P=0.011). In the delayed ASCT cohort, the median OS in respective groups were 73 and 30 months respectively (P<0.001), with elevated CRP being an independent prognostic marker on multivariate analysis (hazard ratio 2.0; 95% confidence interval, 1.0-3.8; P=0.045). Elevated pre-transplant CRP identifies a high-risk population especially in patients undergoing delayed ASCT and should be incorporated in the pre-transplant evaluation.
Assuntos
Proteína C-Reativa/metabolismo , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/sangue , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Taxa de Sobrevida , Adulto JovemRESUMO
Despite enormous advances, management of multiple myeloma (MM) remains challenging. Multiple factors impact the decision to treat or which regimen to use at MM relapse/progression. Recent major randomized controlled trials (RCTs) showed widely varying progression-free survivals (PFS), ranging from a median of 4 months (MM-003) to 23.6 months (ASPIRE). Based on these RCTs, next-generation proteasome inhibitors (carfilzomib and ixazomib), next-generation immunomodulatory agent (pomalidomide), and monoclonal antibodies (elotuzumab and daratumumab) were approved for relapsed and refractory MM. Daratumumab, targeting CD38, has multiple mechanisms of action including modulation of the immunosuppressive bone marrow micro-environment. In addition to the remarkable single agent activity in refractory MM, daratumumab produced deep responses and superior PFS in MM when combined with lenalidomide/dexamethasone, or bortezomib/dexamethasone. Other anti-CD38 antibodies, such as isatuximab and MOR202, are undergoing assessment. Elotuzumab, targeting SLAMF7, yielded superior response rates and PFS when combined with lenalidomide/dexamethasone. New combinations of these next generation novel agents and/or antibodies are undergoing clinical trials. Venetoclax, an oral BH3 mimetic inhibiting BCL2, showed single agent activity in MM with t(11;14), and is being studied in combination with bortezomib/dexamethasone. Selinexor, an Exportin-1 inhibitor, yielded promising results in quad- or penta-refractory MM including patients resistant to daratumumab. Pembrolizumab, an anti-PD1 check-point inhibitor, is being tested in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone. Chimeric antigen receptor-T cells targeting B-cell maturation antigen have yielded deep responses in RRMM. Finally, salvage autologous stem cell transplantation (ASCT) remains an important treatment in MM relapsing/progressing after a first ASCT. Herein, the clinical trial data of these agents are summarized, cautious interpretation of RCTs highlighted, and algorithm for salvage treatment of relapse/refractory MM proposed.
Assuntos
Anticorpos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/terapia , Humanos , Imunoterapia/métodos , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Post-transplant maintenance is widely used in multiple myeloma (MM); however, there is a lack of data on real-world outcomes. We have analyzed 577 patients with newly diagnosed MM undergoing early auto-transplantation between 2010 and 2015. A total of 341, 132 and 104 patients received no, lenalidomide (Len) or bortezomib (Bort) maintenance, respectively. Patients receiving Len or Bort maintenance had a higher incidence of high-risk cytogenetics by fluorescence in situ hybridization (31% (Len) vs 58% (Bort) vs 8% (No); P<0.001). Len maintenance led to a superior progression-free survival (PFS) compared with no maintenance (median, 37 vs 28 months, respectively; P=0.002; adjusted hazard ratio 0.48 (95% CI, 0.35-0.66)), including in subgroups with ISS stage III disease (median, 40 vs 24 months; P=0.008) and high-risk cytogenetics (median, 27 vs 16 months; P=0.032). Bort maintenance did not confer PFS benefit for the entire cohort, but improved PFS in the high-risk cytogenetic subgroup (median, 28 vs 16 months; P=0.035). Discontinuation due to toxicity was seen in 17 and 7% of patients receiving Len or Bort maintenance, respectively. Our results indicate that post-transplant maintenance with Len or Bort is well tolerated in clinical practice and improves PFS in high-risk subgroups of MM patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Lenalidomida/administração & dosagem , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Estadiamento de Neoplasias , Transplante Autólogo , Resultado do TratamentoRESUMO
Hematologic response criteria in light chain (AL) amyloidosis require the difference in involved and uninvolved free light chains (dFLC) to be at least 5 mg/dl. We describe the clinical presentation and outcomes of newly diagnosed amyloidosis patients with dFLC <5 mg/dl (non-evaluable dFLC; 14%, n=165) compared with patients with dFLC ⩾5 mg/dl (evaluable dFLC; 86%, n=975). Patients with non-evaluable dFLC had less cardiac involvement (40% vs 80%, P<0.001), less liver involvement (11% vs 17%, P=0.04) and a trend toward less gastrointestinal involvement (18% vs 25%, P=0.08). However, significantly higher renal involvement (72% vs 56%, P=0.0002) was observed in the non-evaluable dFLC cohort. Differences in treatment patterns were observed, with 51% of treated patients undergoing upfront stem cell transplantation in the non-evaluable cohort compared with 28% in the evaluable dFLC group (P<0.001). Progression-free survival (61 vs 13 months, P<0.001) and overall survival (OS; 101 vs 29 months, P<0.001) were significantly longer in the non-evaluable dFLC cohort. Normalization of involved light chain levels and decrease in dFLC <1 mg/dl (baseline at least 2 mg/dl) were predictive of OS and associated with better dialysis-free survival and may be used for response assessment in patients with non-evaluable FLC levels.
Assuntos
Cadeias Leves de Imunoglobulina/sangue , Amiloidose de Cadeia Leve de Imunoglobulina/sangue , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Fenótipo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Terapia Combinada , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Prognóstico , Modelos de Riscos Proporcionais , Avaliação de Sintomas , Resultado do TratamentoRESUMO
Translocation (11;14) on interphase fluorescent in situ hybridization in plasma cells is regarded as a standard risk prognostic marker in multiple myeloma based on studies conducted before introduction of current therapies. We identified 365 patients with t(11;14), and 730 matched controls:132 patients with non-(11;14) translocations and 598 patients with no chromosomal translocation. The median progression-free survival for the three groups were 23.0 (95% confidence interval (CI), 20.8-27.6), 19.0 (95% CI, 15.8-22.7) and 28.3 (95% CI, 25.7-30.6) months, respectively (P<0.01). The median overall survival (OS) for t(11;14), non-(11;14) translocation and no-translocation groups were 74.4 (95% CI, 64.8-89.3), 49.8 (95% CI, 40.0-60.6) and 103.6 (95% CI, 85.2-112.3) months, respectively (P<0.01). Excluding those with 17p abnormality, the median OS in the three groups were 81.7 (95% CI, 67.0-90.7), 58.2 (95% CI, 47.0-76.4) and 108.3 (95% CI, 92.4-140.1) months, respectively (P<0.01). The above relationship held true in patients with age <65 years, international staging system (ISS) I/II stage or those who received novel agent-based induction. Advanced age (hazard ratio (HR): 1.98), 17p abnormality (HR: 2.2) and ISS III stage (HR: 1.59) at diagnosis predicted reduced OS in patients with t(11;14). These results suggest that outcomes of t(11;14) MM are inferior to other standard risk patients.
Assuntos
Cromossomos Humanos/genética , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Feminino , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Prognóstico , Intervalo Livre de Progressão , Translocação Genética/genética , Adulto JovemRESUMO
Despite therapeutic advances, multiple myeloma remains incurable, with limited options for patients with refractory disease. We conducted a large, multi-cohort clinical trial testing various doses and treatment schedules of pomalidomide and dexamethasone (Pom/dex) in patients with refractory multiple myeloma. Overall, 345 patients were enrolled to six cohorts based on number and type of prior lines of therapy, pomalidomide dose and schedule. Median prior lines of therapy were three with near universal prior exposure to proteasome inhibitors and/or immunomodulatory drugs. A confirmed response rate of 35% was noted for all cohorts (range 23-65%) with higher responses in cohorts with fewer prior lines of therapy. Median time to confirmed response was ⩽2 months and the longest progression-free survival and overall survival seen in any cohort were 13.1 and 47.9 months, respectively. Observed adverse reactions were as expected, with myelosuppression and fatigue being the most common hematologic and non-hematologic adverse events (AEs), respectively. Longer durations of treatment and response, higher response rates and fewer AEs were noted with the 2 mg pomalidomide dose. This is the longest follow-up data for Pom/dex in refractory multiple myeloma and will help shape the real-world utilization of this regimen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Dexametasona/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Retratamento , Análise de Sobrevida , Talidomida/administração & dosagem , Talidomida/análogos & derivados , Resultado do TratamentoRESUMO
High-dose chemotherapy with stem cell transplantation (SCT) is feasible for elderly patients and patients with renal insufficiency. However, the impact of treatment on this patient population is unclear. We evaluated 678 consecutive patients with multiple myeloma who underwent SCT at Mayo Clinic. The complete response rate, time to progression and overall survival was recorded. Patients were stratified according to age (< or =65 or >65 years) and serum creatinine value at the time of transplantation (< or =2 or >2 mg/dl). Patient age did not have an effect on any outcome measure. Creatinine level did not affect complete response rate and time to progression, but patients with creatinine levels above 2 mg/ml had a higher day-100 mortality rate and a shorter overall survival rate. Platelet engraftment was also significantly delayed for patients with renal insufficiency. Selected patients over age 65 years may have outcomes identical to that of younger patients. When compared with patients with creatinine levels less than 2 mg/ml, patients with elevated creatinine levels had similar response rates and time to progression, but their overall survival was inferior. Transplantation should be offered to selected patients over age 65 years or selected patients with creatinine elevation.
Assuntos
Creatinina/sangue , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/sangue , Mieloma Múltiplo/terapia , Fatores Etários , Idoso , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/mortalidade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Taxa de Sobrevida , Fatores de Tempo , Transplante AutólogoRESUMO
Stem cell transplantation is increasingly used in the management of immunoglobulin light-chain amyloidosis (AL). It is considered the standard of care to administer growth factors to accelerate neutrophil recovery after transplantation. However, unique toxicities occur with growth factor use in patients with AL who receive a stem cell transplant. We report a cohort of patients who underwent transplantation without receiving posttransplantation growth factors. In total, 282 patients received a stem cell transplant. A neutrophil count of 500/mul was achieved in 50, 75 and 90% of patients at 14, 16 and 22 days, respectively. A platelet count of 20 000/mul was achieved in 50, 75 and 90% of patients at 14, 20 and 31 days, respectively. Non-staphylococcal bacteremia was detected in 16% of patients. The median hospital stay was 9 days. It is feasible and reasonable to withhold growth factor therapy after autologous stem cell transplantation in patients with AL.