ABSTRACT
Predicting early clinical failure in patients with untreated follicular lymphoma (FL) is important but difficult. This study aimed to determine the incidence and patterns of extranodal (EN) and spleen disease using PET/CT, and assess their utility in predicting early clinical failure. PET/CT images from 613 cases of untreated FL (2003-2016) were reviewed. The location and number of EN sites, patterns of bone involvement, and splenic involvement were recorded. Outcomes were assessed using event-free survival (EFS), overall survival (OS), and early clinical failure at 24 months (EFS24). So, 49% (301/613) of patients had PET/CT-detected EN involvement, and 28% (171/613) had spleen involvement. The presence of ≥2 EN sites, spleen, bone or soft tissue involvement all predicted failure to achieve EFS24. Presence of ≥2 EN sites and bone involvement pattern were also predictive of OS in a univariate analysis. In a multivariate analysis with FLIPI-2 factors, spleen involvement, pattern of bone involvement, and soft tissue involvement independently predicted a lower EFS (HR 1.49 (1.11-2.00), P = .007; HR 1.71 (1.10-2.65), P = .017; and HR 1.67 (1.06-2.62), P = .026, respectively). When the multivariate analysis was performed using PRIMA-PI factors (marrow and B2M), the number of EN sites was an independent prognostic factor for inferior OS (HR 2.28; P = .05). Baseline PET/CT identifies EN involvement in nearly half of patients with untreated FL. The presence of ≥2 EN sites, bone, soft tissue, or splenic involvement predicts early clinical failure. These results, when combined with other factors, may better identify high-risk patients and guide therapy.
Subject(s)
Fluorodeoxyglucose F18/administration & dosage , Lymphoma, Follicular , Positron Emission Tomography Computed Tomography , Spleen/diagnostic imaging , Adult , Aged , Disease-Free Survival , Female , Humans , Lymphoma, Follicular/diagnostic imaging , Lymphoma, Follicular/mortality , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Survival RateABSTRACT
Vitreoretinal lymphoma (VRL) management remains a challenge. We present 72 patients with VRL, diagnosed at Mayo Clinic between 1990-2018. Three nondiffuse large B-cell lymphoma (DLBCL) histology cases were excluded. Among 69 DLBCL, 33 patients had primary VRL (PVRL), 18 concurrent intraocular and central nervous system (CNS) or systemic disease and 18 secondary VRL. Patients received intraocular chemotherapy (intraocular injections of rituximab or metothrexate or steroids or in combination), radiotherapy, systemic or combined systemic plus intraocular treatment in 9, 10, 35, and 15 cases, respectively. Among primary and concurrent VRL, median failure free survival (FFS), CNS relapse-free survival (CNS-RFS) and overall survival (OS) were: 1.8, 4.9, and 4.1 years, respectively; among PVRL, median FFS, CNS-RFS, and OS were: 2.6 year, Not Reached and 9.3 year, respectively. No CNS relapse occurred beyond 4 years in PVRL. Median OS for patients diagnosed between 1990 and 1999 vs between 2000 and 2018 was 1.5 vs 9.4 years, respectively (P = .0002). OS was significantly higher in PVRL, as compared with concurrent VRL (P = .04). Previous immunosuppression and poor performance status were predictive of worse outcome. In PVRL, a combined systemic and intraocular therapy showed higher FFS (P = .002) and CNS-RFS (P = .003), but no differences in OS. Among 18 secondary VRL, at a median follow-up of 1.1 year after vitreoretinal relapse, median FFS and OS were 0.3 and 1.3 years. An improvement in survival of VRL has been observed over the decades. PVRL should undergo combined systemic and intraocular chemotherapy to prevent CNS progression.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Combined Modality Therapy/methods , Lymphoma/therapy , Methotrexate/therapeutic use , Retinal Neoplasms/therapy , Rituximab/therapeutic use , Adult , Aged , Aged, 80 and over , Female , Gamma Rays/therapeutic use , Humans , Injections, Intravenous , Intravitreal Injections , Lymphoma/mortality , Lymphoma/pathology , Male , Middle Aged , Recurrence , Retina/drug effects , Retina/pathology , Retina/radiation effects , Retinal Neoplasms/mortality , Retinal Neoplasms/pathology , Retrospective Studies , Survival Analysis , Treatment Outcome , Vitreous Body/drug effects , Vitreous Body/pathology , Vitreous Body/radiation effectsABSTRACT
The serum immunoglobulin free light chain (FLC) assay quantitates free kappa (κ) and lambda (λ) light chains. FLC elevations in patients with diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL), and chronic lymphocytic leukemia (CLL) are associated with an inferior survival. These increases in FLC can be monoclonal (as in myeloma) or polyclonal. The goal was to estimate the frequency of these elevations within distinct types of B-cell and T-cell non-Hodgkin lymphoma (NHL) and whether the FLC measurements are associated with event-free survival (EFS). We studied serum for FLC abnormalities using normal laboratory reference ranges to define an elevated κ or λ FLC. Elevations were further classified as polyclonal or monoclonal. Four hundred ninety-two patients were studied: 453 B-cell and 34 T-cell NHL patients. Twenty-nine % (142/453) of patients had an elevated FLC of which 10% were monoclonal elevations. Within B-cell NHL, FLC abnormalities were most common in lymphoplasmacytic (79%), mantle cell (68%), and lymphomas of mucosa associated lymphoid tissue (31%); they were least common in follicular (15%). The hazard ratio (HR) for EFS in all patients was 1.41 (95% CI; 1.11-1.81); in all B-cell NHL the HR was 1.44 (95% CI 1.11-1.96); in all T-cell NHL the HR was 1.17 (95% CI 0.55-2.49). FLC abnormalities predicted an inferior OS (HR = 2.75, 95% CI: 1.93-3.90, P < 0.0001). The serum FLC assay is useful for prognosis in both B-cell and T-cell types of NHL. In B-cell NHL further discrimination between a monoclonal and polyclonal elevation may be helpful and should be analyzed in prospective clinical trials.
Subject(s)
Immunoglobulin kappa-Chains/blood , Immunoglobulin lambda-Chains/blood , Lymphoma, B-Cell/blood , Lymphoma, Follicular/blood , Lymphoma, Large-Cell, Immunoblastic/blood , Lymphoma, Mantle-Cell/blood , Lymphoma, T-Cell/blood , Aged , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , B-Lymphocytes/pathology , Clone Cells , Female , Humans , Lymphoma, B-Cell/diagnosis , Lymphoma, B-Cell/mortality , Lymphoma, B-Cell/pathology , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/mortality , Lymphoma, Follicular/pathology , Lymphoma, Large-Cell, Immunoblastic/diagnosis , Lymphoma, Large-Cell, Immunoblastic/mortality , Lymphoma, Large-Cell, Immunoblastic/pathology , Lymphoma, Mantle-Cell/diagnosis , Lymphoma, Mantle-Cell/mortality , Lymphoma, Mantle-Cell/pathology , Lymphoma, T-Cell/diagnosis , Lymphoma, T-Cell/mortality , Lymphoma, T-Cell/pathology , Male , Middle Aged , Prognosis , Survival Analysis , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes/pathologyABSTRACT
Radioimmunotherapy (RIT) for relapsed indolent non-Hodgkin lymphoma produces overall response rates (ORR) of 80% with mostly partial remissions. Synthetic CpG oligonucleotides change the phenotype of malignant B-cells, are immunostimulatory, and can produce responses when injected intratumorally and combined with conventional radiation. In this phase I trial, we tested systemic administration of both CpG and RIT. Eligible patients had biopsy-proven previously treated CD20+ B-cell NHL and met criteria for RIT. Patients received rituximab 250 mg/m(2) days 1,8, and 15; (111) In-ibritumomab tiuxetan days 1, 8; CpG 7909 days 6, 13, 20, 27; and 0.4 mCi/kg of (90) Y-ibritumomab tiuxetan day 15. The doses of CpG 7909 tested were 0.08, 0.16, 0.32 (six patients each) and 0.48 mg/kg (12 patients) IV over 2 hr without dose limiting toxicity. The ORR was 93% (28/30) with 63% (19/30) complete remission (CR); median progression free survival of 42.7 months (95% CI 18-NR); and median duration of response (DR) of 35 months (4.6-76+). Correlative studies demonstrated a decrease in IL10 and TNFα, and an increase in IL1ß, in response to therapy. CpG 7909 at a dose of 0.48 mg/kg is safe with standard RIT and produces a high CR rate and long DR; these results warrant confirmation.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Immunologic Factors/therapeutic use , Lymphoma, Non-Hodgkin/radiotherapy , Oligodeoxyribonucleotides/therapeutic use , Radiopharmaceuticals/therapeutic use , Adult , Aged , Aged, 80 and over , B-Lymphocytes/drug effects , B-Lymphocytes/pathology , Drug Administration Schedule , Humans , Interleukin-10/blood , Interleukin-1beta/blood , Lymphoma, Non-Hodgkin/blood , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/pathology , Male , Middle Aged , Radioimmunotherapy , Recurrence , Survival Analysis , Tumor Necrosis Factor-alpha/blood , Yttrium RadioisotopesABSTRACT
Historically, up to 30% of patients were unable to collect adequate numbers of peripheral blood stem cells (PBSCs) for autologous stem cell transplantation (ASCT). Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) has shown superior results in mobilizing peripheral blood (PB) CD34+ cells in comparison to G-CSF alone, but its high cost limits general use. We developed and evaluated risk-adapted algorithms for optimal utilization of plerixafor. In plerixafor-1, PBSC mobilization was commenced with G-CSF alone, and if PB CD34 on day 4 or day 5 was <10/µL, plerixafor was administered in the evening, and apheresis commenced the next day. In addition, if on any day, the daily yield was <0.5 × 10(6) CD34/kg, plerixafor was added. Subsequently, the algorithm was revised (plerixafor-2) with lower thresholds. If day-4 PB CD34 <10/µL for single or <20/µL for multiple transplantations, or day-1 yield was <1.5 × 10(6) CD34/kg, or any subsequent daily yield was <0.5 × 10(6) CD34/kg, plerixafor was added. Three time periods were analyzed for results and associated costs: January to December 2008 (baseline cohort; 319 mobilization attempts in 278 patients); February to November 2009 (plerixafor-1; 221 mobilization attempts in 216 patients); and December 2009 to June 2010 (plerixafor-2; 100 mobilization attempts in 98 patients). Plerixafor-2 shows a significant improvement in PB CD34 collection, increased number of patients reaching minimum and optimal goals, fewer days of apheresis, and fewer days of mobilization/collection, albeit at increased costs. In conclusion, although the earlier identification of ineffective PBSC mobilization and initiation of plerixafor (plerixafor-2) increases the per-patient costs of PBSC mobilization, failure rates, days of apheresis, and total days of mobilization/collection are lower.
Subject(s)
Algorithms , Hematopoietic Stem Cell Mobilization/economics , Heterocyclic Compounds/economics , Peripheral Blood Stem Cell Transplantation/economics , Adult , Aged , Benzylamines , Case-Control Studies , Costs and Cost Analysis , Cyclams , Female , Hematopoietic Stem Cell Mobilization/methods , Heterocyclic Compounds/administration & dosage , Heterocyclic Compounds/adverse effects , Humans , Lymphoma, Non-Hodgkin/economics , Lymphoma, Non-Hodgkin/therapy , Male , Middle Aged , Plasmacytoma/economics , Plasmacytoma/therapy , Risk Factors , Time Factors , Transplantation, AutologousABSTRACT
Follicular lymphoma is characterized by a highly variable clinical course ranging from early transformation and disease-related mortality to prolonged periods of disease stability or even spontaneous remissions. This clinical heterogeneity is likely explained by differences in the tumor microenvironment, including variable infiltration by monocyte-derived cells. Therefore, we examined the absolute monocyte count obtained from a standard complete blood count with differential at the time of diagnosis as a prognostic factor in a cohort of patients with follicular lymphoma (n = 355) treated at a single institution between 1998 and 2007. We found that the absolute monocyte count at diagnosis is associated with overall survival, independent of the Follicular Lymphoma International Prognostic Index (FLIPI). Furthermore, the absolute monocyte count improved the ability to identify high-risk patients when used in conjunction with the FLIPI. These results further support the central role of non-neoplastic myeloid-lineage cells in follicular lymphoma biology.
Subject(s)
Lymphoma, Follicular/blood , Lymphoma, Follicular/therapy , Monocytes/pathology , Adult , Aged , Aged, 80 and over , Cohort Studies , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Leukocyte Count , Lymphoma, Follicular/diagnosis , Male , Middle Aged , Multivariate Analysis , Prognosis , Risk FactorsABSTRACT
A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib was conducted in 93 adult patients with relapsed or refractory lymphoma. Patients received tipifarnib 300 mg twice daily on days 1-21 of each 28-day cycle. The median number of prior therapies was 5 (range, 1-17). For the aggressive B-cell, indolent B-cell, and T-cell and Hodgkin lymphoma (HL/T) groups, the response rates were 17% (7/42), 7% (1/15), and 31% (11/36), respectively. Of the 19 responders, 7 were diffuse large B-cell non-Hodgkin lymphoma (NHL), 7 T-cell NHL, 1 follicular grade 2, and 4 HL. The median response duration for the 19 responders was 7.2 months (mean, 15.8 months; range, 1.8-62), and 5 patients in the HL/T group are still receiving treatment at 29-64+ months. The grade 3/4 toxicities observed were fatigue and reversible myelosuppression. Correlative studies suggest that Bim and Bcl-2 should be examined as potential predictors of response in future studies. These results indicate that tipifarnib has activity in lymphoma, particularly in heavily pretreated HL/T types, with little activity in follicular NHL. In view of its excellent toxicity profile and novel mechanism of action, further studies in combination with other agents appear warranted. This trial is registered at www.clinicaltrials.gov as #NCT00082888.
Subject(s)
Lymphoma/drug therapy , Quinolones/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Resistance, Neoplasm/drug effects , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/adverse effects , Enzyme Inhibitors/therapeutic use , Farnesyltranstransferase/antagonists & inhibitors , Female , Humans , Lymphoma/pathology , Male , Middle Aged , Quinolones/administration & dosage , Quinolones/adverse effects , Recurrence , Treatment Outcome , Young AdultABSTRACT
Approximately 60% of patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) are curable with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemoimmunotherapy. Epratuzumab (E) is an unlabeled anti-CD22 monoclonal antibody with efficacy in relapsed DLBCL. This phase 2 trial tested the safety and efficacy of combining E with R-CHOP (ER-CHOP) in untreated DLBCL. A secondary aim was to assess the efficacy of interim positron emission tomography (PET) to predict outcome in DLBCL. Standard R-CHOP with the addition of E 360 mg/m(2) intravenously was administered for 6 cycles. A total of 107 patients were enrolled in the study. Toxicity was similar to standard R-CHOP. Overall response rate in the 81 eligible patients was 96% (74% CR/CRu) by computed tomography scan and 88% by PET. By intention to treat analysis, at a median follow-up of 43 months, the event-free survival (EFS) and overall survival (OS) at 3 years in all 107 patients were 70% and 80%, respectively. Interim PET was not associated with EFS or OS. Comparison with a cohort of 215 patients who were treated with R-CHOP showed an improved EFS in the ER-CHOP patients. ER-CHOP is well tolerated and results appear promising as a combination therapy. This study was registered at www.clinicaltrials.gov as #NCT00301821.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/mortality , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antibodies, Monoclonal, Murine-Derived/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Disease-Free Survival , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Female , Follow-Up Studies , Humans , Infusions, Intravenous , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Male , Middle Aged , Positron-Emission Tomography , Prednisolone/administration & dosage , Prednisolone/adverse effects , Prospective Studies , Radiography , Rituximab , Survival Rate , Time Factors , Vincristine/administration & dosage , Vincristine/adverse effectsABSTRACT
PURPOSE: The serum free light chain (FLC) assay quantitates free kappa (κ) and free lambda (λ) immunoglobulin light chains. This assay has prognostic value in plasma cell proliferative disorders. There are limited data on serum FLC in B-cell malignancies. PATIENTS AND METHODS: The association of pretreatment FLC with event-free survival (EFS) and overall survival (OS) in diffuse large B-cell lymphoma (DLBCL) was evaluated in 76 patients from the North Central Cancer Treatment Group trial N0489 (NCT00301821) and 219 patients from the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER). Published reference ranges were used to define an elevated FLC or an abnormal κ:λ FLC ratio. RESULTS: Elevated FLC or abnormal κ:λ FLC ratio was present in 32% and 14% of patients, respectively. Patients with elevated FLC had an inferior OS and EFS in both cohorts compared with patients with normal FLC (N0489: EFS hazard ratio [HR], 3.06; OS HR, 3.16; both P < .02; MER: EFS HR, 2.42; OS HR, 3.40; both P < .001; combined EFS HR, 2.57; OS HR, 3.74; both P < .001). All associations remained significant for EFS and OS after adjusting for the International Prognostic Index (IPI). Abnormal κ:λ FLC ratio was modestly associated with outcome in the combined group (EFS HR, 1.61; OS HR, 1.67; both P = .07), but not in patients without corresponding elevated κ or λ. Elevated FLC was the strongest predictor of outcome in multivariable models with the IPI components. CONCLUSION: Increased serum FLC is an independent, adverse prognostic factor for EFS and OS in DLBCL and warrants further evaluation as a biomarker in DLBCL.
Subject(s)
Biomarkers, Tumor/blood , Immunoglobulin kappa-Chains/blood , Lymphoma, Large B-Cell, Diffuse/immunology , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cohort Studies , Disease-Free Survival , Female , Humans , Immunoglobulin lambda-Chains , Immunologic Techniques , Kaplan-Meier Estimate , Logistic Models , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Odds Ratio , Predictive Value of Tests , Proportional Hazards Models , Registries , Risk Assessment , Risk Factors , Survival Rate , Time Factors , Treatment Outcome , United States , Up-Regulation , Young AdultABSTRACT
High-dose chemotherapy for the management of immunoglobulin light chain amyloidosis remains an effective and viable treatment technique for selected patients with this disorder. We reviewed the medical records of 434 patients uniformly treated with high-dose chemotherapy and autologous stem cell transplant at Mayo Clinic, Rochester, Minnesota, between 8 March 1996 and 13 April 2010. Outcomes, engraftment, and predictors of early mortality were reviewed. Median survival has not been reached for the patients with a complete response, is 107 months for those with a partial response, and is 32 months for patients with no response (pâ<â0.001). The only predictor of survival was cardiac stage (p â<â0.001). The hematologic response rate is predictive for organ response rates. Both hematologic and organ responses are associated with improved survival.
Subject(s)
Amyloidosis/therapy , Hematopoietic Stem Cell Transplantation/methods , Amyloidosis/metabolism , Amyloidosis/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Female , Humans , Immunoglobulin Light Chains/metabolism , Male , Middle Aged , Remission Induction , Retrospective Studies , Survival Analysis , Transplantation Conditioning/methods , Transplantation, Autologous , Treatment OutcomeABSTRACT
Waldenström macroglobulinemia is a B-cell malignancy with lymphoplasmacytic infiltration in the bone marrow or lymphatic tissue and a monoclonal immunoglobulin M protein (IgM) in the serum. It is incurable with current therapy, and the decision to treat patients as well as the choice of treatment can be complex. Using a risk-adapted approach, we provide recommendations on timing and choice of therapy. Patients with smoldering or asymptomatic Waldenström macroglobulinemia and preserved hematologic function should be observed without therapy. Symptomatic patients with modest hematologic compromise, IgM-related neuropathy that requires therapy, or hemolytic anemia unresponsive to corticosteroids should receive standard doses of rituximab alone without maintenance therapy. Patients who have severe constitutional symptoms, profound hematologic compromise, symptomatic bulky disease, or hyperviscosity should be treated with the DRC (dexamethasone, rituximab, cyclophosphamide) regimen. Any patient with symptoms of hyperviscosity should first be treated with plasmapheresis. For patients who experience relapse after a response to initial therapy of more than 2 years' duration, the original therapy should be repeated. For patients who had an inadequate response to initial therapy or a response of less than 2 years' duration, an alternative agent or combination should be used. Autologous stem cell transplant should be considered in all eligible patients with relapsed disease.
Subject(s)
Waldenstrom Macroglobulinemia/diagnosis , Adrenal Cortex Hormones/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Agents/therapeutic use , Blood Viscosity , Drug Therapy, Combination , Humans , Immunologic Factors/therapeutic use , Plasmapheresis , Prognosis , Recurrence , Risk Factors , Rituximab , Time Factors , Treatment Outcome , Waldenstrom Macroglobulinemia/blood , Waldenstrom Macroglobulinemia/drug therapy , Waldenstrom Macroglobulinemia/therapyABSTRACT
The management of atrial fibrillation (AF) following stem cell transplant (SCTX) is often challenging because of the universal presence of profound bone marrow suppression. The incidence of and risk factors for AF/flutter following SCTX are not well known. A total of 395 multiple myeloma (MM) patients consecutively underwent SCTX between 2002 and 2005 at the Mayo Clinic, and 383 of whom, mean age 57 +/- 9 years, had no history of evidence of AF/flutter constituted the study population. During 1,002 person-years of follow up, 39 (10%) patients developed first AF/flutter (incidence of 39 per 1,000 person years), and 28 of these (72%) occurred within 21 days of SCTX. In multivariable-adjusted analyses, weight gain of > or = 7% in the 1st week post-SCTX (HR 3.68; P = 0.0120) and presence of diastolic dysfunction at MM diagnosis (HR 2.294; P = 0.0082) were independent predictors of AF/flutter. The risk of AF/flutter post-SCTX increased by about ninefold when both factors were present. Compared to age and sex-matched MM patients without SCTX, the risk of AF/flutter differed significantly only over the 1st year after MM diagnosis, during which SCTX was performed for the majority. Beyond the 1st year, there was no significant difference in risk of AF/flutter between the two groups. The data suggested that SCTX was associated with significantly increased risk of first AF/flutter, which typically occurred within the first 21 days of the transplant. Weight gain of > or = 7% was strongly predictive of first AF/flutter, and the risk was augmented by the presence of diastolic dysfunction at baseline.
Subject(s)
Atrial Fibrillation/epidemiology , Body Weight , Diastole , Multiple Myeloma/therapy , Stem Cell Transplantation , Adult , Aged , Atrial Fibrillation/etiology , Female , Humans , Incidence , Male , Middle Aged , Multiple Myeloma/epidemiology , Retrospective Studies , Risk Factors , Time FactorsABSTRACT
This phase 3, multicenter, randomized (1:1), double-blind, placebo-controlled study evaluated the safety and efficacy of plerixafor with granulocyte colony-stimulating factor (G-CSF) in mobilizing hematopoietic stem cells in patients with multiple myeloma. Patients received G-CSF (10 microg/kg) subcutaneously daily for up to 8 days. Beginning on day 4 and continuing daily for up to 4 days, patients received either plerixafor (240 microg/kg) or placebo subcutaneously. Starting on day 5, patients began daily apheresis for up to 4 days or until more than or equal to 6 x 10(6) CD34(+) cells/kg were collected. The primary endpoint was the percentage of patients who collected more than or equal to 6 x 10(6) CD34(+) cells/kg in less than or equal to 2 aphereses. A total of 106 of 148 (71.6%) patients in the plerixafor group and 53 of 154 (34.4%) patients in the placebo group met the primary endpoint (P < .001). A total of 54% of plerixafor-treated patients reached target after one apheresis, whereas 56% of the placebo-treated patients required 4 aphereses to reach target. The most common adverse events related to plerixafor were gastrointestinal disorders and injection site reactions. Plerixafor and G-CSF were well tolerated, and significantly more patients collected the optimal CD34(+) cell/kg target for transplantation earlier compared with G-CSF alone. This study is registered at www.clinicaltrials.gov as #NCT00103662.
Subject(s)
Granulocyte Colony-Stimulating Factor/therapeutic use , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cell Transplantation/methods , Heterocyclic Compounds/therapeutic use , Multiple Myeloma/drug therapy , Adolescent , Adult , Aged , Benzylamines , Cyclams , Female , Granulocyte Colony-Stimulating Factor/adverse effects , Granulocyte Colony-Stimulating Factor/pharmacology , Heterocyclic Compounds/adverse effects , Heterocyclic Compounds/pharmacology , Humans , Male , Middle Aged , Multiple Myeloma/surgery , Transplantation, AutologousABSTRACT
We report on the feasibility of outpatient transplant in 716 patients undergoing autologous stem cell transplant for multiple myeloma at Mayo Clinic's site in Rochester, MN, from January 1, 2000, through October 31, 2007. We also report on the development and effect of a multidisciplinary quality initiative implemented by the Mayo Clinic Blood and Marrow Transplant Program involving physicians, nurses, pharmacists, dietitians, and financial specialists for outpatient management of patients undergoing stem cell transplant. This approach uses an electronic ordering system for diagnostic tests and chemotherapy to minimize medical errors. Analysis of hospitalization trends since inception of the program showed that 278 (39%) of the 716 patients treated completed the transplant procedure as outpatients. The median duration of hospitalization for all patients was 4 days; age and serum creatinine levels were predictive of the need for and duration of hospitalization. We also assessed recent treatment-related mortality rates during a 33-month period after implementation of the program (between January 1, 2005, and October 1, 2007). The 100-day survival rate was 99.5% for patients with low-risk myeloma (transplant during first plateau; n=201) and 97.2% for patients with high-risk myeloma (refractory, relapsing or second or greater plateau; n=71). The overall 100-day survival rate was 98.9%. Our experience shows that outpatient transplant is feasible for all patients with multiple myeloma and results in shorter hospital stays and low treatment-related mortality rates.
Subject(s)
Ambulatory Surgical Procedures/methods , Multiple Myeloma/surgery , Quality Assurance, Health Care , Stem Cell Transplantation/methods , Aged , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Minnesota/epidemiology , Multiple Myeloma/mortality , Retrospective Studies , Survival Rate/trends , Time Factors , Transplantation, AutologousABSTRACT
The aim of this study was to learn the toxicity and efficacy of adding 4 doses of rituximab to a standard platinum-based salvage regimen for relapsed CD20+ B-cell non-Hodgkin lymphoma. Patients were treated with rituximab 375 mg/m(2) days 1,8,15, 22 (cycle 1 only); cisplatin 100 mg/m(2) over 24 h on day 3, cytosine arabinoside 2 g/m(2) IV every 12 h x two doses on day 4, dexamethasone 40 mg PO/IV days 3-6, and G-CSF days 5-14. The ORR was 82% (47/57) with 33% (19/57) complete remissions and 49% (28/57) partial remissions. The duration of response (DR) for the 47 responders was 10.5 months (95% CI: 5.3-16.8). The median time to progression (TTP) was 10.3 months (95% CI: 5.3-14.0), the median event-free survival (EFS) was 5.3 months (95% CI: 3.9-11.0), and the median overall survival was 30.5 months (95% CI: 17.8-60.6). We conclude that rituximab can be safely added to standard DHAP.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Neoplasm Recurrence, Local/drug therapy , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived , Cisplatin/therapeutic use , Cytarabine/therapeutic use , Dexamethasone/therapeutic use , Female , Humans , Lymphoma, B-Cell, Marginal Zone/drug therapy , Lymphoma, Follicular/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Mantle-Cell/drug therapy , Male , Maximum Tolerated Dose , Middle Aged , Prognosis , Rituximab , Salvage Therapy , Treatment OutcomeABSTRACT
PURPOSE: Autograft absolute lymphocyte count (A-ALC) affects survival after autologous stem cell transplantation (ASCT) in non- Hodgkin lymphoma (NHL). AMD3100, a CXCR4 antagonist, mobilizes CD34+ stem cells in patients with NHL undergoing ASCT. We sought to study the impact of AMD3100 on A-ALC collection in patients with NHL undergoing ASCT. PATIENTS AND METHODS: The primary endpoint of the study was to assess the association between AMD3100 and A-ALC collection. We compared 7 consecutive patients with NHL mobilized with AMD3100 and granulocyte colony-stimulating factor with 29 control patients with NHL mobilized with granulocyte colony-stimulating factor alone. RESULTS: Higher median A-ALCs were observed in the AMD3100 group compared with the control group (4.16 x 10(9) lymphocytes/kg vs. 0.288 x 10(9) lymphocytes/kg; P < 0.0001). With a median follow-up of 20 months (range, 4-24 months), no relapses were reported in the AMD3100 group compared with 15 of 29 in the control group (P < 0.02). CONCLUSION: Our data suggest that AMD3100 affects A-ALC and clinical outcome in patients with NHL undergoing ASCT.
Subject(s)
Heterocyclic Compounds/pharmacology , Heterocyclic Compounds/therapeutic use , Lymphocytes/drug effects , Lymphoma, Non-Hodgkin/therapy , Stem Cell Transplantation/methods , Adult , Aged , Benzylamines , Cyclams , Disease-Free Survival , Female , Humans , Lymphocyte Count , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Transplantation Conditioning , Transplantation, Autologous , Treatment OutcomeABSTRACT
BACKGROUND: In this pilot study, the authors assessed the feasibility of combination epratuzumab and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (ER-CHOP) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: Patients received chemotherapy on the following schedule: epratuzumab 360 mg/m2, rituximab 375 mg/m2, and standard-dose CHOP every 3 weeks for 6 to 8 cycles. The primary endpoint was the incidence of grade 4 neutropenia and grade 3 or 4 antibody infusional toxicity. Secondary endpoints were the complete response (CR) rate, the overall response rate (ORR), and progression-free survival (PFS). Weekly blood counts were obtained to monitor hematologic toxicity. Fifteen patients were enrolled and treated. Baseline patient characteristics included a median age of 63 years (range, 42-78 years), 60% of patients had stage III or IV disease, 7 patients had a low-risk International Prognostic Index (IPI) score (0 or 1), 7 patients had an intermediate-risk IPI score (2 or 3), and 1 patient was high risk. RESULTS: Grade 3 or 4 neutropenia was observed in 14 patients (93%) or in 28 of 92 treatment cycles (30%). Three patients developed grade > or =3 infection or fever. Eleven patients (73%) required dose reductions. No grade 3 antibody infusion-related toxicity was reported. Thirteen of 15 patients responded (ORR, 87%,), including 10 CRs (67%), 3 partial responses (20%), 1 patient with stable disease, and 1 patient with disease progression. At a median follow-up of 30 months, 13 of 15 patients remained alive. The 1-year PFS and OS rates were 93% and 100%, respectively; and the 2-year PFS and OS rates were 86% and 86%, respectively. CONCLUSIONS: ER-CHOP every 21 days was feasible as treatment for newly diagnosed patients with DLBCL. A Phase II multicenter study is underway.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, B-Cell/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Adult , Aged , Antibodies, Monoclonal, Humanized , Antibodies, Monoclonal, Murine-Derived , Cyclophosphamide/therapeutic use , Disease-Free Survival , Doxorubicin/therapeutic use , Female , Humans , Male , Middle Aged , Pilot Projects , Prednisone/therapeutic use , Rituximab , Treatment Outcome , Vincristine/therapeutic useABSTRACT
PURPOSE: Rituximab is a chimeric antibody that induces B-cell apoptosis and recruits immune effector cells to mediate cell lysis. Interleukin-12 (IL-12) facilitates cytolytic responses by T cells and natural killer cells. This phase II study was done to determine the efficacy and toxicity of IL-12 in combination with rituximab in patients with B-cell non-Hodgkin's lymphoma (NHL). EXPERIMENTAL DESIGN: Fifty-eight patients with histologically confirmed relapsed B-cell NHL were randomized to receive concurrent treatment with rituximab and IL-12 (arm A) or rituximab with subsequent treatment with IL-12 after documented nonresponse or progression after rituximab (arm B). Treatment consisted of 375 mg/m2 rituximab on days 1, 8, 15, and 22 and 300 ng/kg IL-12 given s.c. twice weekly starting on day 2 for arm A or upon progression for arm B. RESULTS: The overall response rate was 37% (11 of 30) in arm A and 52% (13 of 25) in arm B. All of the responses seen in arm B occurred while patients received rituximab, and no responses occurred during treatment with subsequent IL-12. The median duration of response was 16 months for arm A and 12 months for arm B. Biopsy specimens were serially obtained in a subset of patients and showed that changes in gene expression were different when cells from the peripheral blood were compared with cells from lymph node biopsies. CONCLUSIONS: The concomitant use of IL-12 and rituximab had modest disease activity in patients with B-cell NHL, but the sequential administration of IL-12 after rituximab did not result in additional clinical responses.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Interleukin-12/therapeutic use , Lymphoma, B-Cell/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/toxicity , Antibodies, Monoclonal, Murine-Derived , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/toxicity , Drug Administration Schedule , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Interleukin-12/toxicity , Lymphoma, B-Cell/genetics , Lymphoma, B-Cell/immunology , Lymphoma, Non-Hodgkin/genetics , Lymphoma, Non-Hodgkin/immunology , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Patient Selection , RNA, Neoplasm/genetics , RNA, Neoplasm/isolation & purification , Rituximab , T-Lymphocytes/immunologyABSTRACT
Histological transformation of low-grade non-Hodgkin lymphoma (NHL) to diffuse large cell NHL is well recognized and is associated with a poor prognosis. We sought to determine the overall outcome and the factors that affect survival in patients with histological transformation of low-grade NHL. Between November 1979 and September 2000, 93 patients who developed transformed lymphoma were identified. The median time to transformation was 4.2 years from the original diagnosis. The median age at transformation was 63 years. Seventy-eight percent had stage III or IV disease. Fifty-seven percent had extranodal involvement, including bone marrow; 33% had an elevated lactate dehydrogenase. The International Prognostic Index (IPI) at transformation was termed the transformation IPI (tIPI); 29% had a tIPI of 0-1, 59% had a tIPI of 2-3 and 8% had a tIPI of 4-5. At a median follow-up of 15 months from histological transformation, 20 of 93 patients (22%) were alive. The median survival from transformation was 15 months (4 months to 19.7 years). On univariate analysis, the following factors at the time of histological transformation were associated with an improved survival: low tIPI (P = 0.009), time to transformation > 4 years (P = 0.02), age < or = 60 years (P = 0.02) and stage I or II disease (P = 0.04). On multivariate analysis, factors that remained significant included a low tIPI (P = 0.0001) and a time to transformation > 4 years (P = 0.004). tIPI correlated with overall survival (OS); IPI 0-1, median OS 38 months; IPI 2-3, median OS 12 months; IPI 4-5, median OS 4 months. In conclusion, tIPI at the time of histological transformation is an important predictor of OS. A time to transformation > 4 years from diagnosis is associated with better OS.