Mieloma múltiple en Chile: Respuesta a tratamiento en pacientes con mieloma múltiple elegibles para trasplante autólogo de progenitores hematopoyéticos / Response rates to first-line treatment in eligible patients to autologous stem transplantation in Chile

Background The treatment of choice of newly diagnosed multiple myeloma (NDMM) is an induction with proteasome inhibitors followed autologous stem cell transplantation (HSCT). Since 2013, the treatment of these patients in the public system is based on CTD (cyclophosphamide, thalidomide, and dexamethasone). Aim To evaluate the response rates achieved with CTD, and the results of HSCT in patients with NDMM in the public setting. Material and Methods Data from patients considered as candidates for HSCT from different centers of the National Adult Antineoplastic Drug Program (PANDA, for its acronym in Spanish), diagnosed between 2013 and 2017, was analyzed. The response to treatment of first and second lines of treatment was evaluated, in addition to the results of HSCT. An optimal Response was defined as the sum of strict complete remission, complete remission and very good partial response (sCR, CR and VGPR). Results One hundred and seventy-seven patients were analyzed, 54% women, and 53% with IgG multiple myeloma. Information about the international staging system was retrieved in 127 patients (71%). Seventeen percent were ISS I, 22% in ISS II and 32% ISS III. CTD was used as first treatment in 106 patients (60%), and cyclophosphamide, bortezomib and dexamethasone (CyBorD) in 13 (7%). As first line, CTD had an overall response of 50.9%, and CyBorD of 76.9%. Thirty patients were treated with bortezomib as second line treatment. Forty patients (22%) underwent HSCT. The 5-year Overall Survival (OS) in transplanted patients and non-transplanted patients was 100 and 62% respectively (p < 0.01). Conclusions The response rate achieved by CTD in these patients is suboptimal. The response to CyBorD was better.

Mieloma múltiple en Chile: pasado, presente y futuro del programa nacional de drogas antineoplásicas (PANDA). Revisión de 1.103 pacientes / Survival of 1, 103 Chilean patients with multiple myeloma receiving different therapeutic protocols from 2000 to 2016

Background: Multiple myeloma (MM) is one of the most common malignancies found in hematology. Aim: To describe the features of patients with MM and perform a survival analysis according to the different treatment protocols used between 2000 and 2016. Material and Methods: Analysis of the database of the Chilean national anti-neoplastic drug program. Information was obtained from 1,103 patients, with a median age of 64.5 years (range 27-95) and a male to female ratio of 1:1.2. Results: The mean overall survival (OS) of patients receiving or not receiving Thalidomide was 46 and 30 months, respectively (p < 0.01). The mean OS of patients treated before 2007 (treated with melphalan and prednisone) and between 2007 and 2012 (treated with thalidomide and dexamethasone) was 36 and 48 months respectively. In the group starting in 2013 (treated with cyclophosphamide, thalidomide and dexamethasone) the median survival had not been reached at 20 months of follow up (p = 0.01 for all comparisons). Autologous transplantation (AT) was carried out in only 18% of the eligible patients. The median OS of the patients who receive an AT had not been reached at 48 month compared with 36 month among those who did not received the procedure (p < 0.01). Conclusions: Even though overall survival has improved with time, new drugs must be introduced in our protocols to obtain similar results to those obtained worldwide.

Survival analysis in patients with metastatic spinal disease: the influence of surgery, histology, clinical and neurologic status / Análise de sobrevida em pacientes com doença metastática espinhal: influência da cirurgia, histologia, status clínico e neurológico

Spine is the most common site for skeletal metastasis in patients with malignancy. Vertebral involvement quantification, neurological status, general health status and primary tumor histology are factors to set surgical planning and therapeutic targets. We evaluated the impact of general clinical and neurological status, histologic type and surgery in survival. Method : The study sample consisted of consecutive patients admitted from July 2010 to January 2013 for treatment. Results : Sixty eight patients were evaluated. 23 were female and 45 were male. Main primary neoplasic sites were: breast, prostate, lung/pleura and linfoproliferative. Thirty three out of 68 received surgical treatment, 2 received percutaneous biopsy and 33 had nonsurgical treatment. Survival : Log Rank curves revealed no statistical significant difference according to histological type, surgical approach and Frankel Score. Karnofsky Score was statistically different. Conclusion : Histological type and clinical status were statistically associated with life expectancy in vertebral metastatic disease. .

A coluna vertebral é o sítio mais comum de metastases ósseas. A quantificação do acometimento vertebral, o status neurológico, status clínico e histologia do tumor primário são fatores importantes para planejamento cirúrgico e metas terapêuticas. Nós avaliamos o impacto do status clinico geral e neurológico, tipo histológico e cirurgia na sobrevida de pacientes com metástases espinhais. Método : A amostra consistiu de pacientes consecutivamente admitidos de Julho de 2010 a Janeiro de 2013. Resultados : Sessenta e oito pacientes foram avaliados. 23 eram mulheres e 45 eram homens. Os principais sítios primários foram mama, próstata, pulmão e linfoproliferativos. Trinta e três realizaram tratamento cirúrgico, 2 realizaram biópsia percutânea e 33 tiveram tratamento conservador e radioterapia. Conclusão As curvas Log Rank não revelaram significância quanto à cirurgia e escore de Frankel, mas revelaram associação com Karnofsky e tipo histológico. .

Are the binary typology models of alcoholism valid in polydrug abusers ?

Objective: To evaluate the dichotomy of type I/II and type A/B alcoholism typologies in opiate-dependent patients with a comorbid alcohol dependence problem (ODP-AP). Methods: The validity assessment process comprised the information regarding the history of alcohol use (internal validity), cognitive-behavioral variables regarding substance use (external validity), and indicators of treatment during 6-month follow-up (predictive validity). Results: ODP-AP subjects classified as type II/B presented an early and much more severe drinking problem and a worse clinical prognosis when considering opiate treatment variables as compared with ODP-AP subjects defined as type I/A. Furthermore, type II/B patients endorse more general positive beliefs and expectancies related to the effect of alcohol and tend to drink heavily across several intra- and interpersonal situations as compared with type I/A patients. Conclusions: These findings confirm two different forms of alcohol dependence, recognized as a low-severity/vulnerability subgroup and a high-severity/vulnerability subgroup, in an opiate-dependent population with a lifetime diagnosis of alcohol dependence. .

Patterns of Treatment for Metastatic Pathological Fractures of the Spine: The Efficacy of Each Treatment Modality

BACKGROUND: Metastatic pathological fractures of the spine are a major problem for cancer patients; however, there is no consensus on treatment strategy. The purpose of this study was to evaluate various treatment options by analyzing their patterns for metastatic pathological fractures of the spine. METHODS: In this study, 54 patients (male:female = 36:18) who were diagnosed with metastatic pathological fractures of spine were recruited. Demographic data, origin of cancer, type of treatment, and results were obtained from electronic medical records. Treatment options were divided into radiotherapy (RT), vertebroplasty (VP) or kyphoplasty (KP), operation (OP), and other treatments. Treatment results were defined as aggravation, no response, fair response, good response, and unknown. The survival time after detection of pathologic fractures was analyzed with the Kaplan-Meier method. RESULTS: The mean age of the patients was 62.3 years. Hepatocellular carcinoma was the most common cancer of primary origin (n = 9), followed by multiple myeloma (n = 8). RT was the most common primary choice of treatment (n = 29, 53.7%), followed by OP (n = 13, 24.1%), and VP or KP (n = 10, 18.5%). Only 13 of 29 RT cases and 7 of 13 OP cases demonstrated a fair or good response. The mean survival time following detection of pathological spinal fractures was 11.1 months for 29 patients, who died during the study period. CONCLUSIONS: RT was the most common primary choice of treatment for metastatic pathological fractures of the spine. However, the response rate was suboptimal. Although OP should be considered for the relief of mechanical back pain or neurologic symptoms, care should be taken in determining the surgical indication. VP or KP could be considered for short-term control of localized pain, although the number of cases was too small to confirm the conclusion. It is difficult to determine the superiority of the treatment modalities, hence, a common guideline for the diagnosis and treatment of metastatic pathological fractures of the spine is required.

Experiencia de 22 años de trasplante autólogo de células hematopoyéticas en pacientes con mieloma múltiple o amiloidosis sistémica. 1992-2014 / Autologous hematopoietic cell transplantation in patients with multiple myeloma. Experience in 53 patients

Background: Autologous hematopoietic cell transplantation (THA) in patients with multiple myeloma and amyloidosis is the standard of care to promote disease free survival and quality of life. Aim: To report our experience with THA in patients with multiple myeloma. Material and Methods: Retrospective review of the hematopoietic cell transplantation database of a hospital of a Medical School. Forty seven patients with multiple myeloma and six with amyloid light chain amyloidosis were identified. Clinical and demographic data were obtained from the records. Results: The overall five year survival of patients was 55%. Transplant-related or non-relapse mortality occurred in 7%. We found no differences in outcomes among patients younger or older than 50 years. Conclusions: Our data supports that THA can be done in our country with similar results to those obtained in international transplantation centers. Chronological age should not be a limitation to offer this therapy to patients with multiple myeloma and amyloidosis.

Predictive Value of Post-Transplant Bone Marrow Plasma Cell Percent in Multiple Myeloma Patients Undergone Autologous Transplantation

BACKGROUND/AIMS: Autologous stem cell transplantation (ASCT) has become the treatment of choice for patients with multiple myeloma (MM). Studies have shown that maintenance treatment with interferon-alpha is associated with improved survival rates following ASCT. However, despite these recent advances in regimes, relapses are inevitable; thus, the prediction of relapse following ASCT requires assessment. METHODS: We retrospectively analyzed 39 patients who received ASCT between 2003 and 2008. All patients received chemotherapy with vincristine, adriamycin, and dexamethasone (VAD), and ASCT was performed following high-dose melphalan conditioning therapy. We evaluated the influence of the post-transplant day +14 (D+14) bone marrow plasma cell percent (BMPCp) (> or = 2 vs. or = 50 vs. or = 50% at diagnosis, CR after 3 cycles of VAD therapy, del (13q) by fluorescence in situ hybridization, and BMPCp > or = 2% at post-transplant D+14 were correlated with PFS and OS. A multivariate analysis revealed that a post-transplant D+14 BMPCp > or = 2% (PFS, hazard ratio [HR] = 4.426, p = 0.008; OS, HR = 3.545, p = 0.038) and CR after 3 cycles of VAD therapy (PFS, HR = 0.072, p = 0.014; OS, HR = 0.055, p = 0.015) were independent prognostic parameters. CONCLUSIONS: Post-transplant D+14 BMPCp is a useful parameter for predicting the outcome for patients with MM receiving ASCT.

Mieloma múltiplo com fratura no colo do úmero: relato de caso / Multiple myeloma with fracture in the neck of the humerus: a case report

O Mieloma Múltiplo (MM) é uma proliferação neoplásica dos plasmócitos. A proporção entre homens e mulheres é de 3:2, sendo mais comum em negros do que em brancos. A incidência aumenta com a idade e pouco se sabe sobre os fatores de risco para o aumento da incidência da neoplasia. Foi realizada uma breve revisão sobre MM e os benefícios do suporte nutricional em uma paciente de 49 anos que desenvolveu uma fratura de úmero e necessitou de internação em hospital público para tratamento de complicações relacionadas à doença.

Multiple myeloma (MM) is characterized by the neoplastic proliferation of a single clone of plasma cells in bone marrow. The proportion between men and women is 3:2, is more common in blacks than in whites. The incidence increases with age and little is known about risk factors for the increased incidence of the neoplasia. We performed a brief review of MM and the benefits of nutritional support in a 49 year old patient who developed a fracture of humerus and required hospitalization in public hospital for the treatment of complications related to the disease.

Prognostic significance of bone marrow histology in multiple myeloma.

BACKGROUND: Bone marrow examination continues to be the cornerstone for establishing the diagnosis of multiple myeloma in association with other clinical and laboratory parameters. Plasma cell morphology has significant correlation with clinical stage and survival. AIMS: To note the bone marrow histology in detail in multiple myeloma and to correlate it with clinical stage and survival. METHODS AND MATERIAL: Fifty-five cases of multiple myeloma diagnosed between January 2001 and December 2006, who had a bone marrow aspiration and biopsy done at the time of diagnosis were included in the present study. STATISTICAL ANALYSIS: SPSS software version 13.0 was used. Clinical stage and plasma cell morphology were correlated using chi square test and Spearman's correlation coefficient. Survival analysis was done using the Kaplan-Meier method. RESULTS: Seventy-six percent patients were in clinical stage III, 17% and 7% were in stage II and I respectively. The clinical stage correlated significantly with plasma cell morphology, percentage of plasma cell infiltration and pattern of infiltration. Plasma cell morphology correlated significantly with bone marrow parameters like percentage infiltrate, pattern of infiltration, degree of fibrosis and mitotic activity. Patients in advanced clinical stage,> 50% plasma cells in the marrow, diffuse pattern of infiltration, high mitosis and increased fibrosis had a shorter median survival than patients with favorable features. CONCLUSIONS: It is recommended that the bone marrow histology be studied in detail in multiple myeloma at diagnosis since it correlates well with the clinical stage and offers useful prognostic information.

Valor pronóstico del nuevo sistema de etapificación internacional en mieloma múltiple: Comparación con el sistema de Durie-Salmon / Prognostic value of the new international staging system in multiple myeloma: Comparison with Durie-Salmon staging system

Background: Since 1975, the Durie-Salmon staging system (D&S) has been a widely accepted prognostic classification of multiple myeloma (MM) patients. Recently, the new International Staging System (ISS) was developed using only the values of albumin and betaZ-microglobulin. Aim: To compare survival of patients with MM treated in six medical centers in Chile according to the D&S system and the new ISS. Material and methods: Retrospective analysis of demographic information, clinical features and survival rate of patients treated between 1998 and 2002, and grouped according to both systems. Results: Information of 81 patients aged 38 to 90 years (43 women) was retrieved. According D&S system 11 percent were in stage I 12 percent in stage II and 73 percent in stage III According to ISS, 34 percent were in stage I 35 percent in stage II and 31 percent in stage III Median of survival of all patients was 32 months. Both staging systems had a prognostic value. However, median survival for the three stages of the ISS system was significantly different (67, 29 and 14 months in stages III and III, respectively, p =0.02). Patients in advanced stages II and III of the ISS, had a higher frequency of anemia, hypercalcemia, renal failure and hypoalbuminemia. In stages II and III of ISS the presence of renal failure was associated with a non significantly different lower survival. Conclusions: The ISS is a simple and effective grouping method for patients with MM, that predicts survival. The presence of renal insufficiency might identify a subgroup of patients included in stages II and III of ISS with a higher mortality.

Mieloma múltiple en Chile: características clínicas y sobrevida / Clinical features and survival of Chilean patients with multiple myeloma

Background: Mortality rate records are the only data available in Chile about the prognosis of patients with multiple myeloma (MM). Aim To characterize clinical features, survival rate and factors related to mortality in cases with MM treated in six large medical centers in Chile. Material and Method: Retrospective analysis of demographic data, clinical features and survival rate records of patients with MM, collected between 1998 and 2002. Survival curves were generated and a multivariate analysis of factors associated to early mortality was carried out. Results: Data from 245patients aged 38 to 95years (129 women) was collected. Fifty two percent had an IgG myeloma, 25 percent had and IgA and 6.1 percent had light chains myeloma. According to Durie and Salmon staging system, 8,2 percent were in Stage 112.6 percent in Stage II, 60.5 percent in Stage III and in 18.8 percent the information about staging was not available. Fifty percent had an hemoglobin level below 10 g/dL, 30 percent had a serum creatinine over 2 mg/dL and 28 percent had a serum calcium level over 10.5 mg/dL. Median survival was 33 months. Twenty percent of patients died within the first six months after diagnosis (early mortality). Predictive factors for early mortality were male sex, thrombocytopenia, anemia, renal failure, hypercalcemia, a beta2-microglobulin >5.5 mg/L and a serum albumin level <3.5 g/dL. There was a correlation between the number of bad prognosis factors present and the probability of early mortality. Conclusions: This group of Chilean patients with MM presented a short survival time, and 20 percent died within the first six months after diagnosis. More than a half of cases were diagnosed at an advanced stage (Durie and Salmon Stage III). Several factors were associated to early mortality, two of which (beta 2-microglobulin and serum albumin), are included in the new International Staging System for MM.

Fractura en hueso patológico como factor pronóstico de sobrevida en mieloma múltiple de alta masa celular / Pathological fracture as a prognostic factor of survival in multiple myeloma of high celular mass

El mieloma múltiple es una neoplasia de las células plasmáticas que ha permanecido incurable y que tiene como complicaciones la destrucción ósea, la falla renal, la hipercalcemia y la hiperuricemia. El objetivo principal del trabajo fue establecer un factor pronóstico de sobrevida de acuerdo al perfil temporal de presentación de la fractura en hueso patológico. De un total de 96 casos, se revisaron retrospectivamente 79 pacientes diagnosticados como mieloma múltiple de alta masa celular en el Hospital Dr. Gustavo Fricke, entre enero del 1996 y septiembre del 2005. Se encontró una sobrevida promedio de 25 meses y una distribución de la patología según el sexo de 1:1. Sin embargo, los hombres tuvieron la mitad de sobrevida que las mujeres. Así también se encontró que un tercio de los pacientes presentó la fractura o falta renal como debut del mieloma, teniendo una sobrevida significativamente menor.

The Efficacy of High-dose Melphalan with Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma

Although high-dose therapy (HDT) with autologous hematopoietic stem cell transplantation (ASCT) is widely accepted as an effective and safe consolidation therapy for multiple myeloma (MM), few reports on its efficacy are available in Korea. We present the results of a prospective phase II study, involving 33 patients with MM treated with HDT with ASCT. The treatment consisted of 4 courses of VAD (vincristine, adriamycin, dexamethasone) induction, peripheral blood stem cell collection, and high-dose melphalan with stem cell infusion. The overall response rate was 93%, with 45% of patients having complete responses. The toxicity was predictable and tolerable. With a median follow-up of 27.6 months, the 2-year event free survival rate was 43%. At the time of writing, the median overall survival duration had not been reached with 2-year survival and projected 3-year survival rates of 81% and 74%, respectively. The overall survival was significantly better than that of the historical control patients (N=82) treated with conventional chemotherapy at our institution. The results suggest that HDT with ASCT is a valuable first or second-line treatment for patients with MM.

Clinical significance of microvessel density in multiple myeloma patients

To investigate the role of angiogenesis in multiple myeloma (MM), bone marrow biopsy from 75 adults with newly diagnosed, untreated MM were evaluated. Microvessels were scored in at least 3 areas ( x 200 fields) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for CD34. Prognostic variables were also evaluated for the overall survival. Microvessel counts were significantly higher in patients with MM (n=69.42+/-9.67), compared with control (n=26.81+/-2.85). Microvessel density had a weak correlation with percentage of bone marrow plasma cells. By univariate analysis, age, beta2-microglobulin, serum albumin, serum creatinine, serum calcium, hemoglobin, platelet count, and bone marrow plasma cell percentage were correlated with survival. By multivariate analysis, age, serum albumin, serum creatinine, hemoglobin, platelet count and bone marrow plasma cell percentage were correlated with overall survival, whereas microvessel density was not. In summary, microvessel density in bone marrow of MM is significantly increased compared to control, but was not correlated with overall survival. Further studies regarding angiogeneic molecules are needed to determine the functional role of angiogenesis in MM.

Tratamento do mieloma múltiplo com VMCP: revisäo de 52 casos / Treatment of multiple myeloma with VMCP: review of 52 cases

Cinqüenta e dois pacientes estudados entre novembro de 1987 e agosto de 1992 tendo sido submetidos a um ou mais ciclos de quimioterapia com VMCP (vincristina 2mg IV dl; melphalan 4 mg/m² VO d2-5; ciclofosfamida 100 mg/m² VO d2-5 e prednisona 100 mg VO d2-5 - repetidos a cada 28 dias, ou conforme a toxicidade hematológica). Vinte e seis pacientes foram submetidos a radioterapia concomitante. Foi utilziado o estadiamento proposto pelo SWOG (Durie e Salmon, 1975), onde 15 (28,8 por cento) pacientes foram estadiados como IIIA e 32 (61,5 por cento) como IIIB, quatro (7,4 por cento como II e um (2,2 por cento como I. Os critérios de resposta foram os mesmos adotados pelo SWOG; porém, consideramos também como Resposta Parcial (RP) a melhora do PS em um ponto ou mais. Sete pacientes entraram em Remissäo Completa, 12 em Remissäo Parcial e 20 foram considerados com Doença Estável e 13 näo responderam ao tratamento. A Sobrevida Mediana para todos os pacientes, calculada pelo método de Kaplan-Meier, foi de 41 meses. A toxicidade foi tolerável na maioria dos pacientes, sendo grau 3-4 em 16 (30,8 por cento) pacientes em pelo menos um episódio. A principal toxicidade dose limitante foi hematológica. Três pacientes morreram por leucopenia e infecçäo e um por toxicidade gastrointestinal (7,6 por cento). Oito pacientes estäo perdidos do follow-up. Os autores consideram o esquema eficaz e com resultados compatíveis com os da literatura,com toxicidade dentro das expectativas

Características clínicas e implicaçöes prognósticas do acometimento renal no mieloma múltiplo / Clinical characteristics and prognosis implications of renal involvement in multiple myeloma

O envolvimento renal no mieloma múltiplo tem sido associado com pior prognóstico destes pacientes. A influência da insuficiência renal no quadro clínico e no prognóstico de portadores de mieloma múltiplo foi estudada, retrospectivamente, em 45 pacientes. Pacientes com insuficiência renal, à primeira visita, apresentaram maior freqüência de perda de peso, proteinúria e hipercalcemia. Entre os pacientes com insuficiência renal, as médias de uricemia e VHS foram maiores e a média do hematócrito foi menor. Näo houve diferença com relaçäo a edema, hipertensäo arterial, fraturas e dores ósseas. A regressäo da insuficiência renal ocorreu em 47% dos casos, o que se deu mais freqüentemente no primeiro mês de seguimento. A média da creatinina foi mais baixa entre os pacientes com insuficiência renal reversível. A mediana da sobrevida foi: pacientes com insuficiência renal: 11 meses; pacientes com funçäo renal normal: 50 meses. Entre os pacientes com insuficiência renal, aqueles que apresentaram recuperaçäo da funçäo renal mostraram uma mediana de sobrevida maior (24 meses) do que aqueles com insuficiência renal irreversível (1 mês). Em conclusäo: o envolvimento renal no mieloma múltiplo é comum e freqüentemente reversível. Pacientes com insuficiência renal tiveram pior prognóstico; entre os pacientes com insuficiência renal, a normalizaçäo da funçäo renal conferiu melhor prognóstico