RESUMEN

Fludarabine (Flu) and melphalan (Mel) reduced-intensity conditioning is frequently used for allogenic hematopoietic cell transplant (allo-HCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, there is limited evidence on the impact of Mel dosing on toxicities and clinical outcomes of allo-HCT. We retrospectively compared 8/8 HLA-matched donor allo-HCT outcomes of 345 patients with AML or MDS receiving total Mel dose of 100 mg/m2 (Mel-100, n = 62) versus 140 mg/m2 (Mel-140, n = 283) in combination with Flu. Median age at allo-HCT was 66 years and median follow-up was 36.5 months. For Mel-100 versus Mel-140 groups, any grade gastrointestinal (GI) toxicity rates were 40.3% versus 67.8% (P < .001), day 100 grade II to IV acute graft-versus-host disease (GVHD) rates were 21.0% versus 43.1% (P = .001) and 2-year chronic GVHD rates were 17.4% versus 27.1% (P = .033). In multivariable analysis, Mel-140 resulted in higher risks of GI toxicity (HR = 1.83, P = .013), grade II to IV acute GVHD (HR=2.35, P = .003), and moderate/severe chronic GVHD (HR = 3.13, P = .007). Total Mel dose had no independent impact on oral mucositis, nonrelapse mortality, relapse, relapse-free survival, and overall survival. While independent validation of our observation is warranted, our findings support using Mel-100 in combination with Flu to minimize allo-HCT toxicities and morbidities related to GVHD.

Asunto(s)

Ciclofosfamida , Trasplante de Células Madre Hematopoyéticas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Etnicidad , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Inmunosupresores/uso terapéutico , Trasplante Homólogo , Resultado del Tratamiento , Grupos Raciales , Prueba de Histocompatibilidad

RESUMEN

PURPOSE: We investigated whether a dendritic cell (DC) vaccine transduced with an adenoviral vector encoded with full-length survivin (Ad-S), with mutations neutralizing its antiapoptotic function, could safely generate an immune response and deepen clinical responses when administered before and after autologous stem cell transplant (ASCT) for multiple myeloma. PATIENTS AND METHODS: This phase I first-in-human trial (NCT02851056) evaluated the safety of DC:Ad-S in newly diagnosed multiple myeloma not having achieved complete response with induction, given 7 to 30 days prior to stem cell collection and 20 to 34 days after ASCT. Anti-survivin antibodies and CD4+ and CD8+ specific T cells were quantified. RESULTS: A total of 14 patients were treated and 13 included in the primary efficacy analysis. No serious adverse events were attributed to DC:Ad-S vaccine. Detectable anti-survivin antibodies increased from baseline in 9 of 13 (69%) patients, and 11 of 13 (85%) mounted either a cellular or humoral immune response to survivin. Seven patients had an improved clinical response at day +90, all of whom had mounted an immune response, and 6 of 7 patients remain event-free at a median follow-up of 4.2 years. Estimated progression-free survival at 4 years is 71% (95% confidence interval, 41-88). CONCLUSIONS: Two doses of DC:Ad-S, one given immediately before and another after ASCT, were feasible and safe. A high frequency of vaccine-specific immune responses was seen in combination with durable clinical outcomes, supporting ongoing investigation into the potential of this approach. See related commentary by Dhodapkar, p. 4524.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Survivin , Autoinjertos , Trasplante Autólogo , Inmunidad , Células Dendríticas , Trasplante de Células Madre Hematopoyéticas/efectos adversos

RESUMEN

INTRODUCTION: Before 2021, the combination of bortezomib, cyclophosphamide, and dexamethasone (VCd) was one of the most used upfront therapy for systemic immunoglobulin light chain (AL) amyloidosis. Recently, daratumumab in combination with VCd resulted in improved outcomes compared to VCd. However, it's still unclear the role of cyclophosphamide in this combination. MATERIALS AND METHODS: We conducted this retrospective single-institutional study to compare the outcomes of upfront bortezomib and dexamethasone with or without cyclophosphamide (VD vs. VCd). RESULTS: Of 136 total patients, 62 received VD and 74 received VCd. The median age was 64 and the median number of organs involved was 2. Hematologic response was achieved among 73.4% patients in the VD arm and 85.9% in the VCd arm at 3 months (P = .15). Best organ response was not different between 2 arms (34.1% vs. 52.9% for VD and VCd arms, respectively; P = .28). After a median follow-up of 24.4 months, 2-year OS for VD and VCd arm was 70.6% and 84.6% respectively. The median overall survival was 70 months for VD arm and not reached for VCd arm (P = .30). There was no statistically significant difference in median time to next therapy (9.3 vs. 13.5 months for VD and VCd arms, respectively. P = .99). CONCLUSION: the addition of cyclophosphamide to VD was not associated with improved outcomes of patients with AL amyloidosis in this retrospective study.

Asunto(s)

Amiloidosis , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Amiloidosis/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/uso terapéutico , Ciclofosfamida/uso terapéutico , Dexametasona/uso terapéutico , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/tratamiento farmacológico , Persona de Mediana Edad , Estudios Retrospectivos

RESUMEN

Systemic glucocorticoids remain the standard treatment for gastrointestinal (GI) acute graft-versus-host disease (aGVHD) despite their toxicity and incomplete efficacy. Controlled trials have tested poorly absorbable steroids as adjuncts with systemic glucocorticoids, but only small case series have reported treatment with poorly absorbed beclomethasone dipropionate (BDP) and budesonide (BUD) alone. Our team has adopted the practice of administering BDP or BDP+BUD without systemic glucocorticoids as first-line therapy for isolated upper GI (UGI) aGVHD. We report results in 76 patients treated with BDP alone and in 81 patients treated with BDP+BUD, with allocation by physician choice. Almost all patients received peripheral blood stem cells (92%) from a fully HLA-matched related or unrelated donor (80%) after myeloablative conditioning (76%) for acute leukemia (49%), myelodysplastic syndrome (17%), non-Hodgkin lymphoma (14%), or another hematopoietic disorders (20%). After 28 days of treatment with BDP, 46% of the patients had a complete response (CR) and 10% had a partial response (PR); after 200 days, 61 (80%) patients were alive, 34% maintained a CR, and 3% maintained a PR, whereas 53% required additional immunosuppression (IS). After 28 days of treatment with BDP+BUD, 67% had a CR and 10% a PR; after 200 days, 74 (91%) patients were alive, 46% maintained a CR, and 2% maintained a PR, whereas 43% required additional IS. Among the entire cohort of 157 patients, 66 (42%) were treated successfully without systemic glucocorticoids. This study reports the efficacy of poorly absorbable steroids alone for patients with isolated UGI aGVHD. Prospective trials should test for the potential advantages of BDP and BUD use over systemic glucocorticoids.

Asunto(s)

Antiinflamatorios , Beclometasona , Budesonida , Enfermedad Injerto contra Huésped , Adulto , Anciano , Antiinflamatorios/uso terapéutico , Beclometasona/uso terapéutico , Budesonida/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos

RESUMEN

Prognostic biomarkers in allogeneic hematopoietic cell transplantation (allo-HCT) are needed to improve risk assessment and help guide therapeutic and surveillance strategies to mitigate the risk of death from the procedure. We previously identified hypoalbuminemia at day +90 post-transplantation as an independent predictor of increased nonrelapse mortality (NRM) and inferior overall survival (OS) in patients with acute myelogenous leukemia and myelodysplastic syndrome who were treated with an allo-HCT. Here, we aim to confirm the prognostic significance of day +90 hypoalbuminemia in 783 patients, median age 52 years (range, 18 to 76), who received an allo-HCT for various hematologic malignancies and bone marrow failure syndromes. Multivariate analysis for NRM demonstrated a negative effect of low serum albumin levels (<3.0 versus 3.0 to 3.5 versus >3.5 g/dL) at day +90 post-transplantation (hazard ratios, 8.03 [95% CI, 3.59 to 17.97] versus 2.84 [95% CI, 1.59 to 5.08] versus reference; P < .0001). This was also the case for OS (hazard ratios, 6.86 [95% CI, 4.24 to 11.10] versus 1.52 [95% CI, 1.05 to 2.20] versus reference; P < .0001). Patients with hypoalbuminemia at day +90 post-transplantation are more likely to die from causes other than relapse, particularly infections. This large study confirms the ability of day +90 serum hypoalbuminemia to predict worse NRM and inferior OS. Presence of hypoalbuminemia at day +90 should drive a more rigorous real-time surveillance strategy considering the anticipated high-risk of NRM and poor survival in these patients. Future studies should consider incorporating day +90 serum albumin levels in prognostic models of NRM and OS.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas/mortalidad , Hipoalbuminemia/diagnóstico , Valor Predictivo de las Pruebas , Adolescente , Adulto , Anciano , Femenino , Humanos , Hipoalbuminemia/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Factores de Tiempo , Receptores de Trasplantes , Trasplante Homólogo/mortalidad , Adulto Joven

RESUMEN

Graft-versus-host disease (GvHD) remains a major cause of transplant-related mortality. Interleukin-2 (IL-2) plus sirolimus (SIR) synergistically reduces acute GvHD in rodents and promotes regulatory T cells. This phase II trial tested the hypothesis that IL-2 would facilitate STAT5 phosphorylation in donor T cells, expand regulatory T cells, and ameliorate GvHD. Between 16th April 2014 and 19th December 2015, 20 patients received IL-2 (200,000 IU/m2 thrice weekly, days 0 to +90) with SIR (5-14 ng/mL) and tacrolimus (TAC) (3-7 ng/mL) after HLA-matched related or unrelated allogeneic hematopoietic cell transplantation (HCT). The study was designed to capture an increase in regulatory T cells from 16.0% to more than 23.2% at day +30. IL-2/SIR/TAC significantly increased regulatory T cells at day +30 compared to our published data with SIR/TAC (23.8% vs. 16.0%, P=0.0016; 0.052 k/uL vs. 0.037 k/uL, P=0.0163), achieving the primary study end point. However, adding IL-2 to SIR/TAC led to a fall in regulatory T cells by day +90 and did not reduce acute or chronic GvHD. Patients who discontinued IL-2 before day +100 showed a suggested trend toward less grade II-IV acute GvHD (16.7% vs. 50%, P=0.1475). We surmise that the reported accumulation of IL-2 receptors in circulation over time may neutralize IL-2, lead to progressive loss of regulatory T cells, and offset its clinical efficacy. The amount of phospho-STAT3+ CD4+ T cells correlated with donor T-cell activation and acute GvHD incidence despite early T-cell STAT5 phosphorylation by IL-2. Optimizing IL-2 dosing and overcoming cytokine sequestration by soluble IL-2 receptor may sustain lasting regulatory T cells after transplantation. However, an approach to target STAT3 is needed to enhance GvHD prevention. (clinicaltrials.gov identifier: 01927120).

Asunto(s)

Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Interleucina-2/uso terapéutico , Linfocitos T Reguladores/efectos de los fármacos , Adulto , Anciano , Antibióticos Antineoplásicos/uso terapéutico , Esquema de Medicación , Femenino , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Sirolimus/uso terapéutico , Análisis de Supervivencia , Linfocitos T Reguladores/metabolismo , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven

RESUMEN

We conducted a phase 1/2 trial evaluating the combination of cyclophosphamide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone (CVDD) for newly diagnosed multiple myeloma (MM). The primary objective of the phase 1 was to evaluate the safety and tolerability of maximum planned dose (MPD) and the phase 2 was to assess the overall response rate. Patients received 6-8 cycles of CVDD at four dose levels. There were no dose-limiting toxicities. The MPD was cyclophosphamide 750 mg/m(2) IV on day 1, bortezomib 1.3 mg/m(2) IV on days 1, 4, 8, 11, pegylated liposomal doxorubicin 30 mg/m(2) IV on day 4, and dexamethasone 20 mg orally on the day of and after bortezomib (21-d cycle). Forty-nine patients were treated at the MPD of which 22% had high-risk myeloma. The most common grade ≥3 toxicities included myelosuppression, infection, and fatigue. Overall response and complete response rates were 91% and 26% in standard-risk, and 100% and 58% in high-risk cohort, respectively. After a median follow-up of 34 months, the median progression-free survival was 31.3 months. The 2-yr overall survival was 91.1% in the standard-risk and 88.9% in the high-risk cohort, respectively. CVDD regimen was well tolerated and was highly active in newly diagnosed MM.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/análogos & derivados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Tasa de Supervivencia

RESUMEN

Our previous phase I/II trial of pegylated liposomal doxorubicin (PLD), low-dose dexamethasone, and lenalidomide in patients with relapsed and refractory myeloma showed an overall response rate of 75%, with 29% achieving ≥ VGPR. Here, we investigated this combination (PLD 30 or 40 mg/m(2) intravenously, day 1; dexamethasone 40 mg orally, days 1-4; lenalidomide 25 mg orally, days 1-21; administered every 28 days) in a phase II study in patients with newly diagnosed symptomatic multiple myeloma to determine its efficacy and tolerability (ClinicalTrials.gov NCT00617591). At best response, patients could proceed with high-dose melphalan or with maintenance lenalidomide and dexamethasone. In 57 patients, we found that the overall response rate and rate of very good partial response and better on intent-to-treat, our primary endpoints, were 77.2% and 42.1%, respectively, with responses per the International Myeloma Working Group. Median progression-free survival was 28 months (95% CI 18.1-34.8), with 1- and 2-year overall survival rates of 98.1 and 79.6%. During induction, grade 3/4 toxicities were neutropenia (49.1%), anemia (15.8%), thrombocytopenia (7%), fatigue (14%), febrile neutropenia (8.8%), and venous thromboembolic events (8.8%). During maintenance, grade 3/4 toxicities were mainly hematologic. We found this combination to be active in patients with newly diagnosed myeloma, with results comparable to other lenalidomide-based induction strategies without proteasome inhibition. In addition, maintenance therapy with lenalidomide was well tolerated.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/terapia , Talidomida/análogos & derivados , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/administración & dosificación , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Lenalidomida , Quimioterapia de Mantención/efectos adversos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Estadificación de Neoplasias , Polietilenglicoles/administración & dosificación , Inducción de Remisión , Talidomida/administración & dosificación , Trasplante Autólogo , Resultado del Tratamiento

RESUMEN

Lenalidomide and bortezomib have not been compared prospectively and are currently used in sequence for patients with multiple myeloma; however, it is unknown whether a sequence of administration could result in improved outcomes. We retrospectively reviewed electronic records of patients with multiple myeloma who had used both agents in sequence at our institution: 97 patients had lenalidomide first and 111 had bortezomib first. On multivariable analysis, the sequence of therapy was not associated with outcome. These findings were confirmed with instrumental variable analyses. Finally, use of bortezomib first was associated with improved survival for patients with baseline renal insufficiency.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Ácidos Borónicos/administración & dosificación , Bortezomib , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Lenalidomida , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Pronóstico , Pirazinas/administración & dosificación , Inducción de Remisión , Estudios Retrospectivos , Tasa de Supervivencia , Talidomida/administración & dosificación , Talidomida/análogos & derivados

RESUMEN

One limitation of reduced-intensity preparative regimens is potential for graft failure. We have developed a regimen that targets CD4(+) lymphodepletion to ensure early and durable engraftment. The primary endpoint was achievement of ≥50% CD3(+) donor chimerism by day +28. Forty-two patients (median age, 53 years; range, 29 to 73 years) received pentostatin 4 mg/m(2) i.v. on days -28, -21, and -14 when the CD4(+) cell count was >100 cells/µL and on days -4 and -3 regardless of CD4(+) level. Rituximab 375 mg/m(2) was administered to patients with CD20(+) malignancies on days -21, -14, -7, +1, and +8. Busulfan 200 mg/m(2) i.v. was administered on days -4 and -2 at a dose to target a cumulative AUC dose of 16,000 (±10%) µmol·min/L. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus plus methotrexate in 86% of patients. Donors were matched-related (47%), matched unrelated (43%), or mismatched unrelated (10%). Chronic lymphocytic leukemia (45%) and follicular non-Hodgkin lymphoma (14%) were the most common diagnoses. Disease status at initiation of the preparative regimen was complete remission in 22%, partial response in 55%, and stable/progression in 24%. The median percent CD4(+) cell count decrease from baseline (day -28) was 52% to day -21, 66% to day -14, 62% to day -7, and 91% to day 0. At day +28, all 42 patients (100%) had ≥50% CD3(+) donor chimerism. No patient experienced graft failure. Overall response rate was 82% (complete remisson, 67%). The day +100 cumulative incidence of grade II-IV acute GVHD was 59% (grade III-IV acute GVHD, 19%), and the 2 year cumulative incidence of chronic GVHD was 69% (moderate/severe, 58%). Nonrelapse mortality was 2% at day +100 and 17% at 2 years. Two-year PFS was 55%, and OS was 68%. This regimen ensures durable engraftment, is effective against persistent disease, and results in relatively low mortality from causes other than relapse.

Asunto(s)

Antineoplásicos/uso terapéutico , Busulfano/uso terapéutico , Linfocitos T CD4-Positivos/efectos de los fármacos , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas , Pentostatina/uso terapéutico , Acondicionamiento Pretrasplante , Enfermedad Aguda , Adulto , Anciano , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Enfermedad Crónica , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/patología , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/patología , Humanos , Depleción Linfocítica , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Análisis de Supervivencia , Trasplante Homólogo

RESUMEN

We report a case of a female patient with Durie-Salmon stage 3A/ISS stage I IgG kappa multiple myeloma (MM) who developed encephalopathy after high-dose melphalan and hematopoietic stem cell transplant (HSCT). The most common etiologies for encephalopathy such as infection, narcotic medications, metabolic-electrolyte disturbance, stroke, and central nervous system (CNS) hemorrhages were ruled out. The patient recovered from the altered mental status spontaneously. The possibilities of melphalan-induced encephalopathy versus critical-state delirium versus hypercytokinemia induce encephalopathy were contemplated.

RESUMEN

We conducted a Phase 1/2 study of bortezomib administered in combination with high-dose melphalan followed by tandem autologous transplants in patients with primary resistant multiple myeloma. Thirty patients received two cycles of salvage bortezomib followed by stem cell mobilization with granulocyte colony-stimulating factor and harvest. Melphalan 100 mg/m(2) per day on two consecutive days was administered, immediately followed by one dose of bortezomib (dose escalation) and stem cell infusion. The median beta 2-microglobulin was 4·35 mg/l (range: 1·8-11·4); albumin was 37 g/l (range: 3·1-4·9); high-risk karyotypes were noted in 45% of patients. The maximum planned dose of bortezomib at 1·3 mg/m(2) was well tolerated and a formal maximum tolerated dose was not determined. The peak of best overall response (≥partial response) and complete response rates after tandem transplants were 84% and 36%, respectively. With a median follow-up of 48 months, the median progression-free survival was 15 [95% confidence interval (CI): 11-21] months and the median overall survival was 35 (95% CI: 22-43) months. Correlative studies demonstrated decreased expression of BRCA2 (P = 0·0072) and FANCF (P = 0·0458) mRNA following bortezomib treatment. Bortezomib combined with high-dose melphalan is a well-tolerated conditioning with some activity in patients with resistant myeloma.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple/terapia , Terapia Recuperativa , Acondicionamiento Pretrasplante , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ácidos Borónicos/administración & dosificación , Bortezomib , Progresión de la Enfermedad , Proteínas del Grupo de Complementación de la Anemia de Fanconi/metabolismo , Femenino , Humanos , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Mieloma Múltiple/mortalidad , Pirazinas/administración & dosificación , Transducción de Señal , Análisis de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento

RESUMEN

BACKGROUND: PCL carries a poor prognosis and the optimal management remains unknown. PATIENTS AND METHODS: To evaluate the outcome of patients with PCL in the era of novel agents and innovative transplantation strategies, we conducted a review of patients with PCL who were treated at our institution from August 2003 to October 2009. Our primary endpoint was to determine overall survival, which was calculated from time of PCL diagnosis to death or last follow-up. Secondary endpoints included response rates and analyses regarding how the novel agents and presence of adverse cytogenetic analyses affected outcomes. RESULTS: We identified 25 patients with PCL (13 with primary PCL [pPCL], 12 with secondary PCL [sPCL]) from our institution. Eighteen patients received bortezomib-based regimens, 19 received high-dose melphalan followed by autologous hematopoietic stem cell transplantation (HCT), and 6 underwent allogeneic HCT. The median overall survival for all patients was 23.6 months. Bortezomib-treated patients had a median survival of 28.4 months vs. 4.0 months for the non-bortezomib-treated group (P < .001). CONCLUSIONS: Our analysis suggests that patients with PCL who were treated with bortezomib and/or allogeneic HCT had improved outcomes.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia de Células Plasmáticas/terapia , Adulto , Anciano , Femenino , Humanos , Leucemia de Células Plasmáticas/tratamiento farmacológico , Leucemia de Células Plasmáticas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento

RESUMEN

Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoproliferative disorder. HIV-negative PBL has not been extensively reported. Nine HIV-negative PBL patients evaluated at Moffitt Cancer Center were studied. Eight patients had extranodal diseases. All patients were treated with CHOP or hyper-CVAD. Responses were observed in 8 cases (7 complete, 1 partial responses). Four patients underwent consolidation with autologous hematopoietic stem cell transplant (HSCT) in first complete remission (CR1). At median follow-up of 23.9 months, 7 patients were alive and 5 were disease-free. Aggressive induction chemotherapy and consolidation with autologous HSCT in CR1 might be considered for patients with HIV-negative PBL.

Asunto(s)

Linfoma de Células B/terapia , Anciano , Terapia Combinada , Femenino , Estudios de Seguimiento , Infecciones por VIH/epidemiología , Humanos , Inmunofenotipificación , Linfoma de Células B/epidemiología , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento

Asunto(s)

Sistema Biliar/patología , Leucemia Mieloide/patología , Infiltración Leucémica/patología , Hígado/patología , Enfermedad Aguda , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

We examined pharmacokinetic-targeted IV busulfan (75-170 mg/m(2), with target AUC of 3500-6000 µmol min) and fludarabine (40 mg/m(2)) × 4 days with rituximab (t-IV Bu/Flu + rituximab) 375 mg/m(2) on days +1 and +8 followed by allogeneic hematopoietic cell transplantation in 19 patients (median age 56, range 35-68 years) with CD20+ lymphoid malignancies. Median time to neutrophil and platelet engraftment was 15 and 12 days. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 58% (95% confidence interval, CI 39-85%), and chronic GVHD was 50% (95% CI 28-88%). With a median follow up of 7 (range 1-31) months, overall response was observed in 15, and stable or progressive disease in 4. Overall survival at 1 year was 67%. Engraftment, chimerism, and infectious complications did not differ significantly from a contemporaneous non-rituximab containing comparator group. The addition of rituximab 375 mg/m(2) to t-IV Bu/Flu does not appear to adversely affect engraftment, donor chimerism, or increase the risk of infectious complications.

Asunto(s)

Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Busulfano/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Leucemia Linfoide/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Acondicionamiento Pretrasplante , Vidarabina/análogos & derivados , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Antígenos CD20/metabolismo , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Busulfano/administración & dosificación , Busulfano/efectos adversos , Estudios de Cohortes , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Linfoide/metabolismo , Leucemia Linfoide/terapia , Linfoma/metabolismo , Linfoma/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Rituximab , Vidarabina/administración & dosificación , Vidarabina/efectos adversos , Vidarabina/uso terapéutico

RESUMEN

Toxicity associated with a second autologous peripheral blood stem cell transplant (APBSCT) in patients who relapse following initial APBSCT for multiple myeloma (MM) has not been well described. We conducted a retrospective, case-series of 25 consecutive patients who received a second APBSCT for relapsed or progressive disease following prior APBSCT to describe associated toxicity. Grade 3 or 4 toxicities were observed in 92% of patients after each APBSCT. More patients developed an elevated serum creatinine (4%vs. 36%; p = 0.011) following the second APBSCT. Median time to neutrophil engraftment was 10 days following both transplants (p = 0.428). Platelet engraftment was delayed by 2 days after the second APBSCT (median 12 vs.14 days; p < 0.025). There were two deaths before day 100. In conclusion, patients who undergo a second APBSCT for relapsed MM experience more nephrotoxicity. Delayed platelet engraftment and an 8% treatment-related mortality were observed following the second APBSCT.

Asunto(s)

Mieloma Múltiple/terapia , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Recurrencia , Sistema de Registros , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento

RESUMEN

Paclitaxel and G-CSF have been evaluated for HPC mobilization in breast cancer and found to have tolerable toxicity with a predictable time to initiate leukapheresis. However, this approach has not been reported in patients with hematologic malignancies failing prior mobilization. We report a case-series of 26 adults given paclitaxel and G-CSF for HPC mobilization after failure of an initial mobilization. Patients received paclitaxel 250 mg/m(2) followed by G-CSF 10-16 mcg/kg/day. Compared to the initial regimen, paclitaxel mobilization produced greater CD34+ cell yields (median 1.53 x 10(6) CD34+ cells/kg vs. 0.79 x 10(6) CD34+ cells/kg, p = 0.004). Seventy-six percent of patients initiated leukapheresis on day 8, the remainder on day 9 or 10. Three patients developed febrile neutropenia resulting in one death prior to leukapheresis. Overall, 73% of patients proceeded with autologous HPC transplant. This case-series suggests paclitaxel may be an option for HPC mobilization in patients failing prior regimens.

Asunto(s)

Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Neoplasias Hematológicas/terapia , Movilización de Célula Madre Hematopoyética/métodos , Paclitaxel/administración & dosificación , Anciano , Antígenos CD34/análisis , Filgrastim , Neoplasias Hematológicas/mortalidad , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucaféresis , Persona de Mediana Edad , Paclitaxel/efectos adversos , Proteínas Recombinantes , Trasplante Autólogo , Insuficiencia del Tratamiento

RESUMEN

INTRODUCTION: There is limited information regarding of use of vascular access devices (VAD) in patients undergoing hematopoietic stem cell transplantation (HSCT). The frequent use of VAD in HSCT and its potential to cause morbidity requires understanding of the general use of VAD in HSCT. MATERIALS AND METHODS: A World Wide Web-based 19-item questionnaire was designed to determine the patterns of use of VAD in patients undergoing HSCT. The questionnaire was sent via electronic mail to the directors of HSCT programs throughout the world. RESULTS: Of the 445 centers surveyed, 163 centers replied for a response rate of 37%. The most commonly used catheter for autologous peripheral blood stem cell (PBSC) harvest is the dual-lumen plasmapheresis/hemodialysis (62%). Of the institutions, 58% utilize the same catheter used for PBSC harvest to provide vascular access support during the transplant. Catheter-related blood stream infection (36%) and withdrawal occlusion (31%) were the most frequently encountered complications of VAD. Of the centers, 65% have established criteria for VAD removal when infection is suspected and 48% when occlusion is suspected. DISCUSSION: Our study demonstrated that there are similarities in the utilization of VAD but also wide differences in the standard procedures for the insertion and care of VAD in the transplant setting. More comprehensive studies are needed to assess the use of central venous catheters in transplant recipients. Important areas for future research include the impact of VAD utilization on the quality of life of transplant recipients and the final consequences of VAD complications.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas/métodos , Cateterismo Venoso Central , Catéteres de Permanencia , Encuestas de Atención de la Salud , Humanos , Internacionalidad , Internet , Encuestas y Cuestionarios , Trasplante