Trends in allogeneic stem cell transplantation for multiple myeloma: a CIBMTR analysis.

Allogeneic hematopoietic cell transplantation in multiple myeloma is limited by prior reports of high treatment-related mortality. We analyzed outcomes after allogeneic hematopoietic cell transplantation for multiple myeloma in 1207 recipients in 3 cohorts based on the year of transplantation: 1989-1994 (n = 343), 1995-2000 (n = 376), and 2001-2005 (n = 488). The most recent cohort was significantly older (53% > 50 years) and had more recipients after prior autotransplantation. Use of unrelated donors, reduced-intensity conditioning and the blood cell grafts increased over time. Rates of acute graft-versus-host (GVHD) were similar, but chronic GVHD rates were highest in the most recent cohort. Overall survival (OS) at 1-year increased over time, reflecting a decrease in treatment-related mortality, but 5-year relapse rates increased from 39% (95% confidence interval [CI], 33%-44%) in 1989-1994 to 58% (95% CI, 51%-64%; P < .001) in the 2001-2005 cohort. Projected 5-year progression-free survival and OS are 14% (95% CI, 9%-20%) and 29% (95% CI, 23%-35%), respectively, in the latest cohort. Increasing age, longer interval from diagnosis to transplantation, and unrelated donor grafts adversely affected OS in multivariate analysis. Survival at 5 years for subjects with none, 1, 2, or 3 of these risk factors were 41% (range, 36%-47%), 32% (range, 27%-37%), 25% (range, 19%-31%), and 3% (range, 0%-11%), respectively (P < .0001).

Outcome of patients with IgD and IgM multiple myeloma undergoing autologous hematopoietic stem cell transplantation: a retrospective CIBMTR study.

INTRODUCTION: Immunoglobulin D (IgD) and IgM multiple myeloma represent uncommon immunoglobulin isotypes, accounting for 2% and 0.5% of cases, respectively. Limited information is available regarding the prognosis of these isotypes, but they have been considered to have a more aggressive course than the more common immunoglobulin G (IgG) and IgA isotypes. In particular, the outcome after autologous hematopoietic stem cell transplantation (auto-HCT) has not been well defined. PATIENTS AND METHODS: Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 36 patients with IgD and 11 patients with IgM myeloma among 3578 myeloma patients who received intensive therapy and auto-HCT over a 10-year period. RESULTS: The progression-free and overall survival probabilities at 3 years were 38% (95% CI, 21%-56%) and 69% (95% CI, 51%-84%) for IgD myeloma, and 47% (95% CI, 17%-78%) and 68% (95% CI, 36%-93%), respectively, for IgM disease. Although formal statistical analysis was limited by the small sample size, these results were comparable to those for IgG and IgA patients autografted during the same time period. Transplantation-related mortality and disease relapse/progression of myeloma were also similar for all isotypes. CONCLUSION: This analysis demonstrates comparable outcomes in all immunoglobulin isotypes. Therefore, auto-HCT should be offered to eligible patients with IgD and IgM myeloma.

Comparison of twin and autologous transplants for multiple myeloma.

Relapse is the overwhelming cause of treatment failure after autologous transplantation for multiple myeloma (MM). For patients with a syngeneic donor, twin transplants provide a healthy graft that is free of myeloma. The relative impact of the graft on posttransplant relapse can be estimated by comparing risk of relapse after hematopoietic cell transplantation from genetically identical twins versus autotransplants because confounding differences in minor or major histocompatibility antigens are absent in the syngeneic transplant setting. Outcomes of 43 subjects who received twin transplants for MM were compared to 170 matched autotransplant recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Multivariate analysis was performed by fitting a Cox model stratified on matched pairs. The matched transplant patients studied were similar with respect to subject-, disease-, and transplant-related characteristics. Cumulative incidence of relapse/progression was significantly lower, and progression-free survival (PFS) was significantly higher following twin transplants. In multivariate analysis, the probability of relapse/progression was lower in twins (relative risk [RR] = 0.49, 95% confidence interval [CI] 0.28-0.86, P = .011). Twin transplants have a significantly lower relapse risk than autotransplants in MM, suggesting that graft composition may impact outcomes following high-dose chemotherapy.

Comparable outcomes in nonsecretory and secretory multiple myeloma after autologous stem cell transplantation.

Nonsecretory myeloma (NSM) accounts for <5% of cases of multiple myeloma (MM). The outcome of these patients following autologous stem cell transplantation (ASCT) has not been evaluated in clinical trials. We compared the outcomes after ASCT for patients with NSM reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) between 1989 and 2003, to a matched group of 438 patients (4 controls for each patient) with secretory myeloma (SM). The patients were matched using propensity scores calculated using age, Durie-Salmon stage, sensitivity to pretransplant therapy, time from diagnosis to transplant, and year of transplant. Disease characteristics were similar in both groups at diagnosis and at transplant except higher risk of anemia, hypoalbuminemia, and marrow plasmacytosis (in SM) and plasmacytoma (more in NSM). Cumulative incidence of treatment-related mortality (TRM), relapse, progression-free survival (PFS), and overall survival (OS) were similar between the groups. In multivariate analysis, based on a Cox model stratified on matched pairs and adjusted for covariates not considered in the propensity score, we found no difference in outcome between the NSM and SM groups. In this large cohort of patients undergoing ASCT, we found no difference in outcomes of patients with NSM compared to those with SM.

Pretransplantation consolidation chemotherapy decreases leukemia relapse after autologous blood and bone marrow transplants for acute myelogenous leukemia in first remission.

Controversy exists over whether pretransplantation consolidation chemotherapy affects the outcome of subsequent autotransplantation for acute myelogenous leukemia (AML). The current study was undertaken to determine the association between previous consolidation and outcome of autotransplantation for AML in first remission. Posttransplantation outcomes of 146 patients receiving no consolidation were compared with those of 244 patients receiving standard-dose (<1 gm/m(2)) and 249 patients receiving high-dose (1-3 gm/m(2)) cytarabine, using proportional hazards regression to adjust for differences in prognostic variables. One-year transplantation-related mortality was similar among the cohorts. Five-year relapse rates were 49% (95% confidence interval CI} = 39%-58%) with no consolidation, 35% (95% CI = 29%-42%) with standard-dose cytarabine, and 40% (95% CI = 33%-48%) with high-dose cytarabine (P = .07). Five-year leukemia-free survival rates were 39% (95% CI = 30%-47%) with no consolidation, 53% (95% CI = 46%-60%) with standard-dose cytarabine, and 48% (95% CI = 40%-56%) with high-dose cytarabine (P = .03). Similarly, 5-year overall survival was better in those patients receiving consolidation: 42% (95% CI = 34%-51%) with no consolidation, 59% (95% CI = 52%-65%) with standard-dose cytarabine, and 54% (95% CI = 46%-61%) with high-dose cytarabine (P = .01). Although most patients received 1 or 2 cycles of consolidation, the number of courses had no detectable effect on transplantation outcome. In multivariate analysis, risks of relapse and treatment failure were lower in the patients receiving consolidation, especially among those patients receiving blood cell grafts. Outcomes with standard-dose and high-dose cytarabine were similar. Based on our findings, we recommend that patients with AML in first remission receive consolidation before undergoing autotransplantation.

A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome.

Bone marrow transplantation (BMT) can cure myelodysplastic syndrome (MDS), although transplantation carries significant risks of morbidity and mortality. Because the optimal timing of HLA-matched BMT for MDS is unknown, we constructed a Markov model to examine 3 transplantation strategies for newly diagnosed MDS: transplantation at diagnosis, transplantation at leukemic progression, and transplantation at an interval from diagnosis but prior to leukemic progression. Analyses using individual patient risk-assessment data from transplantation and nontransplantation registries were performed for all 4 International Prognostic Scoring System (IPSS) risk groups with adjustments for quality of life (QoL). For low and intermediate-1 IPSS groups, delayed transplantation maximized overall survival. Transplantation prior to leukemic transformation was associated with a greater number of life years than transplantation at the time of leukemic progression. In a cohort of patients under the age of 40 years, an even more marked survival advantage for delayed transplantation was noted. For intermediate-2 and high IPSS groups, transplantation at diagnosis maximized overall survival. No changes in the optimal transplantation strategies were noted when QoL adjustments were incorporated. For low- and intermediate-1-risk MDS, delayed BMT is associated with maximal life expectancy, whereas immediate transplantation for intermediate-2- and high-risk disease is associated with maximal life expectancy.

Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group.

All-trans-retinoic acid (ATRA) increases the efficacy of chemotherapy when used for induction and maintenance treatment of acute promyelocytic leukemia (APL), but its role in consolidation is unknown. Since November 1996, 426 patients with newly diagnosed APL have received induction therapy with ATRA and idarubicin. Before November 1999 (LPA96 study), consolidation therapy consisted of 3 courses of anthracycline monochemotherapy. After November 1999 (LPA99 study), patients with intermediate and high risks of relapse received consolidation therapy with ATRA and increased doses of anthracyclines. Of the 384 patients who achieved complete remission (90%), 382 proceeded to consolidation therapy. Seven patients died in remission (1.8%). The 3-year cumulative incidence of relapse for patients in the LPA96 and LPA99 studies was 17.2% and 7.5%, respectively (P =.008). Patients treated with ATRA in consolidation therapy showed an overall reduction in the relapse rate from 20.1% to 8.7% (P =.004). In intermediate-risk patients the rate decreased from 14.0% to 2.5% (P =.006). This improved antileukemic efficacy also translated into significantly better disease-free and overall survival. A risk-adapted strategy combining anthracycline monochemotherapy and ATRA for induction and consolidation therapy of newly diagnosed APL results in improved antileukemic efficacy and a high degree of compliance.

A comparison of allogeneic and autologous bone marrow transplantation for lymphoblastic lymphoma.

Lymphoblastic lymphoma (LBL) is a rare, clinically aggressive neoplasm of the young that frequently involves the bone marrow (BM) and/or central nervous system. Because LBL is similar to acute lymphoblastic leukemia, some centers prefer allogeneic hematopoietic stem cell (SC) transplantation to autologous SC transplantation. We retrospectively analyzed outcomes for patients who underwent autologous (auto, n = 128) or HLA-identical sibling (allo, n = 76) SC transplantations from 1989 to 1998 and were reported to International Bone Marrow Transplant Registry (IBMTR) or Autologous Blood and Marrow Transplant Registry (ABMTR). Allo stem cell transplant (SCT) recipients had higher treatment-related mortality (TRM) at 6 months (18% versus 3%, P =.002), and this disadvantage persisted at 1 and 5 years. Early relapse rates after alloSC transplantation and autoSC transplantation were similar, but significantly lower relapse rates were observed in alloSCT recipients at 1 and 5 years (32% versus 46%, P =.05; and 34% versus 56%, P =.004, respectively). No differences were noted in lymphoma-free survival rates between alloSC transplantations and autoSC transplantations (5-year rates 36% versus 39%, P =.82). AutoSCT recipients had higher overall survival at 6 months (75% versus 59%, P =.01), but survival did not significantly differ between the 2 groups at 1 and 5 years (60% versus 49%, P =.09; 44% versus 39%, P =.47, respectively). Multivariate analyses to account for confounding factors confirmed these results. Independent of SCT type, BM involvement at the time of transplantation and disease status more advanced than first complete remission were associated with inferior outcomes. In summary, alloSC transplantation for LBL is associated with fewer relapses than with autoSC transplantation, but higher TRM offsets any potential survival benefit.

Ocho años de experiencia en una sola institución en transplante autólogo de células progenitoras hematopoyéticas en enfermedades hematológicas malignas y en tumores sólidos / Eight years of experience in a single institution in hematopoietic stem cell autologous transplantation in malignant hematological diseases and in solid tumors

Entre agosto 1991 y diciembre 1998, 400 pacientes (linfoma: 197, leucemia aguda: 86, mieloma múltiple: 70 y tumores sólidos 47) recibieron un trasplante autólogo. Todos los pacientes fueron movilizados con quimioterapia más G-CSF. Luego de la infusión se utilizó G-CSF. La recuperación de neutrófilos fue similar en todos los grupos; en pacientes con leucemia aguda y mieloma múltiple la recuperación de plaquetas fue más lenta. La muerte relacionada al tranplante fue 4.5 por ciento. El estado de la enfermedad al momento del procedimiento fue el principal factor pronóstico. Con una mediana de seguimiento de 23 meses la SLE a 60 meses fue de 46 por ciento para linfomas de bajo grado, 44 por ciento para linfomas de grado alto e intermedio, 58 por ciento para enfermedad de Hodgkin, 45 por ciento para leucemia mieloblástica aguda, 38 por ciento para tumores sólidos y 15 por ciento para mieloma múltiple. A 60 meses la probabilidad actuarial de supervivencia fue 67 por ciento para linfomas de bajo grado, 47 por ciento para linfomas de grado alto e intermedio, 75 por ciento para enfermedad de Hodgkin, 52 por ciento para leucemia mieloblástica aguda, 54 percent para tumores sólidos y 25 por ciento para mieloma múltiple. Se concluye que el trasplante autólogo de progenitores hematopoyéticos indujo una recuperación hematopoyética rápida y completa. Los resultados obtenidos son similares a los publicados en la literatura, siendo discutido el rol en pacientes con tumores sólidos. La muerte relacionada fue baja sin fallos tardíos del injerto.

Ocho años de experiencia en una sola institución en transplante autólogo de células progenitoras hematopoyéticas en enfermedades hematológicas malignas y en tumores sólidos / Eight years of experience in a single institution in hematopoietic stem cell autologous transplantation in malignant hematological diseases and in solid tumors

Entre agosto 1991 y diciembre 1998, 400 pacientes (linfoma: 197, leucemia aguda: 86, mieloma múltiple: 70 y tumores sólidos 47) recibieron un trasplante autólogo. Todos los pacientes fueron movilizados con quimioterapia más G-CSF. Luego de la infusión se utilizó G-CSF. La recuperación de neutrófilos fue similar en todos los grupos; en pacientes con leucemia aguda y mieloma múltiple la recuperación de plaquetas fue más lenta. La muerte relacionada al tranplante fue 4.5 por ciento. El estado de la enfermedad al momento del procedimiento fue el principal factor pronóstico. Con una mediana de seguimiento de 23 meses la SLE a 60 meses fue de 46 por ciento para linfomas de bajo grado, 44 por ciento para linfomas de grado alto e intermedio, 58 por ciento para enfermedad de Hodgkin, 45 por ciento para leucemia mieloblástica aguda, 38 por ciento para tumores sólidos y 15 por ciento para mieloma múltiple. A 60 meses la probabilidad actuarial de supervivencia fue 67 por ciento para linfomas de bajo grado, 47 por ciento para linfomas de grado alto e intermedio, 75 por ciento para enfermedad de Hodgkin, 52 por ciento para leucemia mieloblástica aguda, 54 percent para tumores sólidos y 25 por ciento para mieloma múltiple. Se concluye que el trasplante autólogo de progenitores hematopoyéticos indujo una recuperación hematopoyética rápida y completa. Los resultados obtenidos son similares a los publicados en la literatura, siendo discutido el rol en pacientes con tumores sólidos. La muerte relacionada fue baja sin fallos tardíos del injerto. (AU)

Leucemia mielomonocítica crónica / Chronic myelomonocytic leukemia

Se estudiaron las biopsias medulares óseas de 10 pacientes con diagnóstico hematológico de Leucemia Mielomonocítica Crónica (LMMC). Los cilindros fueron obtenidos de la cresta ilíaca, descalcificados, incluidos en parafina y los cortes obtenidos coloreados con diversas técnicas. Se estableció estimativamente la celularidad global así como las características madurativas y topográficas de las progenias, cantidad de hemosiderina, magnitud de la trama reticular y otras observaciones complementarias. Los pacientes comprendieron 8 hombres y 2 mujeres, con un rango etario de 63 a78 años y una media de 70 años. Se registró la presencia de síntomas generales en 5 pacientes, hepatomegalia en 8, esplenomegalia en 9 y adenomegalias en 8 pacientes. Todos evidenciaban monocitosis en sangre periférica (> 1 x 10**9/l). Las médulas fueron hipercelulares, con 80 a 100% de celularidad hemopoyética. La serie mieloide mostró maduración completa con topografía conservada y precursores aislados, y presencia de elementos monocitoides más o menos conspicuos. La serie eritroide mostró disminución de grado variable en todos los casos. El sector megacariocítico evidenció alteraciones morfológicas discretas con topografía conservada. La hemosiderina estaba aumentada en 5 casos. La trama reticular se presentó incrementada en 8 pacientes. Como alteraciones asociadas se observó plasmocitosis reactiva en tres casos y cambios óseos en 6 pacientes. En base a los resultados obtenidos se concluye que la LMMC posee un cuadro histológico distintivo, que difiere de las Mielodisplasisa y guarda una relación en ocasiones estrecha, con los Síndromes Mieloproliferativos Crónicos, en especial la Leucemia Mieloide Crónica

Leucemia mielomonocítica crónica / Chronic myelomonocytic leukemia

Se estudiaron las biopsias medulares óseas de 10 pacientes con diagnóstico hematológico de Leucemia Mielomonocítica Crónica (LMMC). Los cilindros fueron obtenidos de la cresta ilíaca, descalcificados, incluidos en parafina y los cortes obtenidos coloreados con diversas técnicas. Se estableció estimativamente la celularidad global así como las características madurativas y topográficas de las progenias, cantidad de hemosiderina, magnitud de la trama reticular y otras observaciones complementarias. Los pacientes comprendieron 8 hombres y 2 mujeres, con un rango etario de 63 a78 años y una media de 70 años. Se registró la presencia de síntomas generales en 5 pacientes, hepatomegalia en 8, esplenomegalia en 9 y adenomegalias en 8 pacientes. Todos evidenciaban monocitosis en sangre periférica (> 1 x 10**9/l). Las médulas fueron hipercelulares, con 80 a 100% de celularidad hemopoyética. La serie mieloide mostró maduración completa con topografía conservada y precursores aislados, y presencia de elementos monocitoides más o menos conspicuos. La serie eritroide mostró disminución de grado variable en todos los casos. El sector megacariocítico evidenció alteraciones morfológicas discretas con topografía conservada. La hemosiderina estaba aumentada en 5 casos. La trama reticular se presentó incrementada en 8 pacientes. Como alteraciones asociadas se observó plasmocitosis reactiva en tres casos y cambios óseos en 6 pacientes. En base a los resultados obtenidos se concluye que la LMMC posee un cuadro histológico distintivo, que difiere de las Mielodisplasisa y guarda una relación en ocasiones estrecha, con los Síndromes Mieloproliferativos Crónicos, en especial la Leucemia Mieloide Crónica (AU)