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W S Velasquez

Publications and source records attributed to W S Velasquez.

At least 19 recordsLinked to original sources
PubMed1999

Rituximab therapy in Waldenstrom's macroglobulinemia: preliminary evidence of clinical activity.

To assess the preliminary efficacy of rituximab therapy in Waldenstrom's macroglobulinemia (WM), we examined the clinical and laboratory data for all patients with WM treated on IDEC Pharmaceuticals sponsored trials and one patient treated at Walter Reed Army Medical Center. Seven symptomatic patients with WM were treated with four (n = 6) or eight (n = 1) weekly infusions of rituximab (375 mg/m2). Patients had received a median of three prior therapies (range 1-4) which included alkylator therapy in all (five patients refractory) and fludarabine in four (all refractory). Therapy was tolerated well in all patients without decrement in cellular immune function or significant infectious morbidity. Partial responses were noted in three of these patients, including two with fludarabine-refractory disease. The median progression-free survival for these patients was 6.6 months (range 2.2-29+ months). These data suggest that rituximab has clinical activity in heavily pre-treated patients with Waldenstrom's macroglobulinemia. Based on these data, clinical studies of Rituximab in previously untreated and treated WM appear indicated.

Aged↗
PubMed1997

[Lymphoma].

Explore the source record for details and available documents.

Adult↗
PubMed1996

Acute myelofibrosis terminating in acute lymphoblastic leukemia: case report and review of the literature.

Acute myelofibrosis (AMF), as defined by an acute panmyelopathy associated with marked megakaryocytic hyperplasia and marrow fibrosis, appears to be a stem cell disorder. Even though it is most difficult to distinguish from various myeloproliferative and myelodysplastic disorders as well as acute myelogenous leukemia, it has rarely been reported to terminate as acute lymphoblastic leukemia (ALL). Only five cases have been reported in the literature; two from the pediatric literature and only three from the adult literature. Of the three adult cases, two were defined by light microscopy alone. Among the cases with follow-up (3/5), all died within 2 weeks to 2 months of diagnosis. We report an additional case in an adult; the ALL was defined by morphology, flow cytometric immunophenotyping, and cytogenetic analysis. The interval from diagnosis of AMF to ALL was 3 months. Our patient was treated with standard therapy for ALL, was in complete remission at last follow-up (3 months off maintenance therapy), and represents the only reported case who attained a complete remission. There are too few cases to determine the prognostic significance of termination of AMF in an acute leukemia of lymphoid origin vs. myeloid origin.

Adult↗
PubMed1996

Antifungal effects of yeast-derived rhu-GM-CSF in patients receiving high-dose chemotherapy given with or without autologous stem cell transplantation: a retrospective analysis.

Systemic fungal infections (SFI) in patients receiving high-dose chemotherapy (HDC) are a frequent cause of morbidity and mortality. Preclinical studies have reported augmented antifungal activity of monocytes, macrophage cells, and neutrophils exposed to certain colony-stimulating factors (CSF), including GM-CSF. We conducted a retrospective descriptive epidemiologic study to examine the characteristics of 145 consecutive patients receiving HDC administered with or without autologous stem cell transplantation (ASCT) and who subsequently received either GM-CSF and G-CSF, G-CSF alone, GM-CSF +/- IL-3 or no CSF. The analysis of this patient population sought to define the incidence of SFI and its relationship to therapy with monocyte/macrophage-stimulating (MMS group) cytokines (GM-CSF and G-CSF; GM-CSF +/- IL-3) or to cytokines which do not result in monocyte/macrophage stimulation (NMMS group, G-CSF alone or no CSF). Risk factors for the development of SFI were balanced between the MMS (n = 70) and NMMS (n = 75) groups. Two patients (2.9%) in the MMS and nine patients (12%) in the NMMS groups developed SFI. The risk ratio for developing SFI in the NMMS group compared to the MMS group was 4.20 (P = 0.023). This relationship was confounded, however, by the diagnosis of hematologic tumor or solid tumor (RR = 3.15, P = 0.082). SFI was the primary cause or major contributing factor in five of the 10 total deaths in our study population. Four SFI-related deaths occurred in the NMMS group and one SFI-related death occurred in the MMS group. Our data suggest a protective role for GM-CSF, IL-3 or other MMS cytokines in preventing SFI in patients receiving HDC. This should be further investigated as a potential complementary approach to conventional strategies in antifungal prophylaxis for patients receiving HDC.

Adult↗
PubMed1995

Significance of tumor size and radiation dose to local control in stage I-III diffuse large cell lymphoma treated with CHOP-Bleo and radiation.

PURPOSE: The purpose of this study was to evaluate the possible effect of adjunctive involved field (IF) radiotherapy on long-term local control for patients with Ann Arbor Stage I-III diffuse large cell lymphoma (DLCL) who achieved a complete remission on a combined modality program which included cyclophosphamide, doxorubicin, vincristine, prednisone, and Bleomycin (CHOP-Bleo). METHODS AND MATERIALS: One hundred and ninety patients with Ann Arbor Stage I-III DLCL were treated with CHOP-Bleo and radiotherapy. Analyses were undertaken to determine (a) response to treatment according to stage, extent of maximum local disease, and irradiation dose either < 40 Gy or > or = 40 Gy and (b) relapse patterns. RESULTS: A complete remission (CR) was achieved in 162 patients. Among patients who achieved a CR, local control was better for those who received tumor doses of > or = 40 Gy (97%) than for those who received < 40 Gy (83%) (p = 0.002.) Among those with extensive local disease, the corresponding control rates were 88% and 71%, respectively. A study of distant relapse patterns following a CR showed that the first relapse usually involved an extranodal site. CONCLUSION: Radiotherapy was an effective adjunctive treatment to CHOP-Bleo for patients with stage I-III DLCL who achieved a CR. Patterns of relapse suggested that total nodal irradiation (TNI) possibly could have benefited a small subset of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Natural killer cell lymphoproliferative disorder of granular lymphocytes presenting as hemolytic anemia: case report and review of the literature.

Lymphoproliferative disorders of granular lymphocytes (LDGLs) have recently been hypothetically defined based on their immunophenotype, function, and clonality. The majority (129/161) of LDGLs are of the T-cell subset, which is typically associated with neutropenia and occasionally with anemia. The remainder (32/161) are of natural killer cell origin. This subset is associated with neutropenia (52% of cases) and anemia (60% of cases). The anemia most often has no immediately apparent cause. The Coombs test was negative in all cases reported. There is only one reported case of an associated Coombs-negative hemolytic anemia. We report an unusual case of natural killer cell LDGL, defined by morphology and immunophenotypic analysis, presenting as a de novo Coombs-negative hemolytic anemia. The anemia was resistant to steroid therapy. Therapeutic splenectomy resulted in a temporary resolution of the hemolytic process. The splenic pathology is also described.

Aged↗
PubMed1995

Risk classification for large cell lymphoma using lactate dehydrogenase, beta-2 microglobulin, and thymidine kinase.

We have previously proposed a staging system for large cell lymphoma using the two serum markers beta-2-microglobulin (B2M) and lactate dehydrogenase (LDH). We recently tested this model in a different cohort of patients with large cell lymphoma and also examined the possible contribution of thymidine kinase (TK), a previously reported serologic prognostic factor. Using an inclusion criteria in the multivariate analysis for both forward and backward selection of p < 0.15, only LDH, B2M, and TK were significant independent prognostic factors for both time to treatment failure (TTF) and survival. Inclusion of TK in the serologic model resulted in three significantly different risk groups for both TTF and survival. Corresponding endpoints at three years were: 1) good risk (no markers elevated, n = 43): 78%, 91%; 2) intermediate risk (1 or 2 markers elevated, n = 47): 41%, 36%; 3) poor risk (3 markers elevated, n = 11): 0%, 0%. This analysis extends the observation of the independent prognostic significance of B2M and LDH. The addition of TK permits a more precise estimate of risk, contributing to the utility of a serological staging system for large cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Pegaspargase versus asparaginase in adult ALL: a pharmacoeconomic assessment.

Asparaginase is an effective treatment for patients with acute lymphocytic leukemia (ALL). Unfortunately, asparaginase therapy is associated with a high incidence of hypersensitivity reactions (up to 73%), including life-threatening anaphylaxis, and its half-life of approximately 20 hours necessitates daily administration. Pegaspargase, a modification of L-asparaginase, has a longer half-life (357 hours), a decreased incidence of hypersensitivity reactions, and when doses every 14 days, provides comparable efficacy to asparaginase; however, it is much more expensive per single-dose vial ($980.00 vs $52.38). To determine the pharmacoeconomic impact of the two agents, we conducted a cost-minimization analysis for three common adult ALL protocols. Results showed that pegaspargase was significantly less costly to payers on an inpatient or outpatient basis and warranted addition to our formulary.

Adult↗
PubMed1994

Intermediate-grade lymphomas treated with cyclophosphamide-doxorubicin- vincristine-prednisone-bleomycin alternated with cyclophosphamide-methotrexate-etoposide-dexamethasone. Application of prognostic models to data analysis.

BACKGROUND: Numerous treatment strategies have been tried with the aim of improving results for patients with intermediate-grade lymphomas (IGL) over those achieved with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo), and numerous prognostic models have been developed to identify and separate risk groups. This study reports on a new protocol for Ann Arbor Stages II-IV IGL that consists of CHOP-Bleo alternated with a new regimen of cyclophosphamide, methotrexate, etoposide, and dexamethasone (CMED) and radiation therapy and demonstrates the usefulness of prognostic models for identifying risk groups and comparing treatment programs. METHODS: One hundred seventy patients with Ann Arbor Stages II-IV IGL were treated with alternating cycles of CHOP-Bleo and CMED for a total of 12 cycles. Involved field radiation therapy was interspersed with courses of chemotherapy for patients with Stage II and Stage III disease. Results were analyzed and compared with those of the authors' previous study of CHOP-Bleo and radiation therapy using the Ann Arbor staging system, their earlier prognostic model, and the recently published International Index. RESULTS: A complete remission occurred in 78% of the patients. The overall 5-year survival rate was 67%. Survival was better for patients with Ann Arbor Stage II disease (80%) than for those with Stage III or Stage IV (67% and 58%, respectively). High tumor burden, above-normal levels of serum lactic dehydrogenase, serum beta 2-microglobulin, and Ann Arbor Stage IV disease were adverse factors. The International Index and the authors' earlier prognostic model separated four prognostic groups. CHOP-Bleo/CMED was generally well tolerated. Neutropenic fever was the major complication that occurred in 25 patients during treatment. Six of these patients died of sepsis. CONCLUSIONS: This study demonstrated that CHOP-Bleo/CMED is a well-tolerated regimen that produced better results than those reported for a former study that used CHOP-Bleo alone. Further, results for CHOP-Bleo/CMED compared favorably with those of other second- and third-generation regimens. The study also validated the usefulness of prognostic models and, in particular, the new International Index for identifying risk groups.

Adolescent↗
PubMed1994

Randomized study of growth factors post-peripheral-blood stem-cell transplant: neutrophil recovery is improved with modest clinical benefit.

PURPOSE: To evaluate the clinical value of growth factors (GFs) with peripheral-blood stem cells (PBSC) collected following mobilization with GFs, we randomized patients to receive or not to receive GFs following transplant. PATIENTS AND METHODS: Thirty-seven patients were apheresed after receiving the combination of granulocyte colony-stimulating factor (G-CSF) with granulocyte-macrophage colony-stimulating factor (GM-CSF) at doses of 10 micrograms/kg/d and 5 micrograms/kg/d, respectively, for 6 days before apheresis and during a median of 4 days of collections. One day after the infusion of autologous marrow and PBSC, patients were randomly assigned to receive no GFs or a combination of G-CSF (7.5 micrograms/kg/d) and GM-CSF (2.5 micrograms/kg/d), both as a 2-hour intravenous (i.v.) infusion twice per day until the neutrophil count was greater than 1,500/microL. RESULTS: The median days to recovery to an absolute neutrophil count (ANC) of 100/microL (9 v 11.5, P = .0005), 500/microL (10 v 16, P = .0004), or 1,000/microL (12 v 21, P = .0008) was shortened with the use of GFs, post-PBSC infusion. In addition, the duration of hospitalization was shorter (19 v 21 days, P = .0112) in the arm receiving GFs post-PBSC infusion. There was no significant difference between the two study arms in the duration of fever, documented septic episodes, or RBC or platelet transfusion requirements. CONCLUSION: Despite faster neutrophil recovery and shortened duration of hospitalization with GFs administered after PBSC transplantation, the measured clinical variables of febrile days, septic episodes, and transfusion requirements were similar between the study arms. The use of GFs post-PBSC transfusion is associated with a modest clinical benefit.

Adult↗
PubMed1994

ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study.

PURPOSE: This study attempted to determine the efficacy of the combination of etoposide (VP-16), methyl-prednisolone, and cytarabine (Ara-C) with or without cisplatin in relapsing and refractory adult lymphoma patients. PATIENTS AND METHODS: The first 63 patients were randomized to receive VP-16 40 mg/m2/d for 4 days, methylprednisolone 500 mg intravenously daily for 5 days, and Ara-C 2 g/m2 intravenously over 2 to 3 hours on day 5 with or without cisplatin 25 mg/m2 IV administered by 24-hour infusion for 4 days (ESHA +/- P). Markedly different responses between ESHA (33%) and ESHAP (75%) led to deletion of the ESHA arm. A total of 122 patients on the ESHAP regimen were studied. RESULTS: Forty-five patients (37%) attained a complete remission (CR) and 33 (27%) attained a partial remission (PR), for a total response rate of 64%. The median duration of CR was 20 months, with 28% of remitters still in CR at 3 years. The overall median survival duration was 14 months; the survival rate at 3 years was 31%. Overall time to treatment failure (TTF) showed 10% of all patients to be alive and disease-free at 40 months. Response and survival rates were similar in patients with low-grade (n = 34), intermediate-grade (n = 67), transformed (n = 18), and high-grade (n = 3) lymphoma. The most significant factors for response and survival by multivariate analysis were the serum lactic dehydrogenase (LDH) level, tumor burden, and age (when analyzed as a continuous variable), while prior CR was highly significant by univariate analysis. A significant difference in survival was noted for patients with normal LDH levels and low- or intermediate-tumor burden or patients with low tumor burden and elevated LDH levels (55% 3-year survival rate) versus patients with elevated LDH levels and intermediate or high tumor burden (< 20%). Major toxicities included myelosuppression, with a median granulocyte count of 500/microL and platelet count of 70,000/microL. CONCLUSION: ESHAP was found to be an active, tolerable chemotherapy regimen for relapsing and refractory lymphoma. Applying a prognostic model based on tumor burden and serum LDH level shows significant differences in survival in this patient population.

Adolescent↗
PubMed1993

Tandem transplants in solid tumors: marrow versus peripheral stem cell transplant: peripheral blood cells as now practiced are not the whole answer.

We have performed sequential studies examining the modification of hematopoietic toxicity after the administration of high-dose cyclophosphamide, etoposide, and cisplatin (CVP). The sequential studies include a comparison of the influence of autologous bone marrow transplantation (ABMT) on hematopoietic recovery after CVP, with or without growth factors. These studies demonstrate a significant shortening of the duration of neutropenia with ABMT, but minimal impact on the number of infectious episodes, when compared to those not receiving ABMT. The addition of mobilized peripheral blood stem cells (PBSC) to ABMT followed by growth factor was found to enhance platelet recovery, but did not significantly further reduce the period of absolute neutropenia. Subsequent studies show that similar early hematopoietic recovery can be achieved by use of peripheral blood stem cells alone, pheresed following several days of subcutaneous administration of recombinant growth factors, but neutrophil recovery is more rapid with use of growth factor after PBSC infusion. Using the product of two phereses for each cycle of recovery appears to result in similar rates of hematopoietic engraftment after each cycle of CVP. In conclusion, the use of peripheral blood stem cells alone following sequential high dose CVP is associated with rapid neutrophil and platelet recovery. Caution should be exercised when using PBSC alone after high dose therapy, due to the lack of platelet recovery in some instances, which can be overcome by reinfusion of backup marrow. Thus, studies evaluating the role of PBSC after high dose therapy should continue.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Hodgkin's disease: study of treatment intensities and incidences of second malignancies.

BACKGROUND: Advances in radiotherapy and chemotherapy have gradually increased cure rates for patients with Hodgkin's disease. With improved long-term survivals, increases in observed second malignancies over those of the general population have been reported as early as 1972. Recently, a number of investigators have suggested that the relative importance of recognized risk factors contributing to the development of acute myelogenous leukemia (AML), non-Hodgkin's lymphomas, and solid tumors may be different. Our study is concerned with the influence of various risk factors on patients who have been treated with modern radiotherapy and combination chemotherapy between 1966 and 1987. PATIENTS AND METHODS: We reviewed the records of 1,022 patients with Hodgkin's disease of whom 1,013 had sufficient data for analysis. Kaplan-Meier methodology was used to calculate overall and determinate survivals and occurrences of acute myelogenous leukemia, non-Hodgkin's lymphoma, and solid tumors. The observed to expected incidences, calculated from the SEER incidence and population files for 1976, were compared. Using Cox's proportional hazards model, the following were analyzed singly for risk significance for the entire population: age, stage, splenectomy, treatment modality, treatment intensity, and number of treated relapses. Separate analyses were performed to determine the relative risks for subsets of the population. These included pelvic radiotherapy for those with stage III disease and specific alkylating agents for patients who were treated with chemotherapy only. RESULTS: Sixty-six instances of second malignancy were documented as follows: AML 14, non-Hodgkin's lymphoma 14, and solid tumors 38. The overall incidence of second malignancy was significantly greater than the expected incidence of 21.75 (p = 0.0001) and it was also significant for AML, non-Hodgkin's lymphoma and solid tumors. Analyses for risk of second malignancy demonstrated that age > or = 40 years, stage III or stage IV disease, and treatment with chemotherapy only were all associated with a significantly higher risk of second malignancy than any of the other factors. However, only treatment with regimens containing nitrogen mustard had a significantly higher risk for second malignancy. Treatment intensity and number of treated relapses had no specific effect on risk. Joint modeling of age, stage, and treatment showed that the combination of age and stage was the most significant risk factor for AML and non-Hodgkin's lymphoma (p = < 0.0003). However, only age was important for solid tumors. CONCLUSIONS: Our analysis suggests that the most critical host factor for developing a second malignancy was age. The fact that patients with stages III and IV disease had an increased risk of second malignancy regardless of age suggests that biologic factors related to the tumor also may have been significant. However, it is possible that the effect of treatment was hidden by stage.

Actuarial Analysis↗
PubMed1993

CHOP-Bleo plus interferon for stage IV low-grade lymphoma.

BACKGROUND: Alpha interferon (IFN) is an effective single agent for patients with low-grade lymphoma, but until 1982 had not been integrated with standard chemotherapy for these patients. Since relapse from complete remission (CR) is the rule for patients with advanced stage low-grade lymphoma, a maintenance IFN schedule was explored for patients in CR. PATIENTS AND METHODS: From 1982-1987, 127 patients with stage IV low-grade lymphoma were treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo) for 9-18 mo. (median 13 mo.), followed by interferon alfa-n-1 (Wellferon) maintenance therapy for 24 mo. for CRs. RESULTS: The overall response rate for the entire treatment program was 73% CR and 23% partial remission. The median follow up was 59 months. At 5 years, survival was 74%, failure-free survival (FFS) 47%, and FFS of CRs 60%. Compared to a group of 96 patients with similar pretreatment clinical features treated with CHOP-Bleo from 1972-1982, this represents a significant improvement for both overall FFS (p = 0.01) and FFS of CRs (P < 0.01). Toxicity from the IFN maintenance was generally acceptable, but even at the modest dose employed in this trial (3 x 10(6) U/m2 three times weekly), dose modification was required in more than 30% of patients, usually because of fatigue. CONCLUSIONS: The integration of IFN and conventional chemotherapy is feasible and effective. Maintenance IFN prolongs remission duration for patients with stage IV low-grade lymphoma.

Adult↗
PubMed1992

Clinical, biologic, and histologic features of late relapses in diffuse large cell lymphoma.

After completing chemotherapy and achieving a complete remission (CR), patients with diffuse intermediate-grade lymphoma and immunoblastic lymphoma are usually considered cured if they are able to maintain that remission continuously for 24 months. Recently, we observed a number of patients with these disorders who relapsed after a continuous CR of greater than or equal to 30 months from the beginning of therapy or 24 months from completing chemotherapy. This finding led us to examine 503 consecutive cases to determine the risk of late relapse and their clinical and biologic features. We found that the overall risk of late relapse of those who attained CR was 6.8%, but several features at presentation were associated with a high risk: (1) the presence of a divergent histology; (2) a sclerosing large cell lymphoma; (3) a diagnosis based on an extranodal site with no nodal tissue available for examination. When none of these features were present, the risk of late relapse was minimal (only 3%). When any of these features was present, the risk was 14%. Most striking was the 43% late relapse rate of patients with divergent histology. All but one of the eight B-cell tumors studied at relapse showed kappa light chain restriction. Five of these eight has a low S phase at the time of relapse, suggesting chemotherapeutic selection of a clone of cells with a low proliferative potential that could have given rise to the late relapse. Nucleic acid flow cytometry and immunophenotypic studies on three tumors at initial diagnosis and after relapse failed to support the hypothesis of a second de novo lymphoma and were consistent with a true recurrence of the original tumor. The results of salvage chemotherapy in this group of late relapses showed a high CR rate (57%) but no evidence of a trend for cure in the time to treatment failure curve. In contrast to the experience with Hodgkin's disease, retreatment with the same or a similar regimen used for the original induction was not associated with durable response. Clinicians should be aware of the potential for a late relapse in cases with divergent histology and the need for new treatment strategies for such cases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Radiotherapy during pregnancy for clinical stages IA-IIA Hodgkin's disease.

Between 1956 and 1990, 775 women were treated for Hodgkin's disease at The University of Texas M.D. Anderson Cancer Center. Of these, 25 (3.2%) were pregnant at diagnosis. Seven of these women were in the first trimester, 10 in the second, and eight in the third. Prior to treatment, three women in the third trimester had normal deliveries, and six patients in the first trimester had abortions. Sixteen patients received radiotherapy for supradiaphragmatic presentations during their pregnancies. All these patients had nodular sclerosing Hodgkin's disease: Two had clinical stage IA presentations and 14 had clinical stage IIA. In two patients radiotherapy (35 Gy) was limited to the neck, three patients were treated definitively to the neck and mediastinum (40 Gy), and 11 patients received mantle irradiation (40 Gy). Four to five half-value layers of lead were used to shield the uterus during radiotherapy. The dose to the fetus was estimated individually in nine patients, using a combination of an Alderson-Rando and a water phantom. The estimated total dose to the mid-fetus ranged from 1.4 to 5.5 cGy for treatment with 6 MV photons, and from 10 to 13.6 cGy for Cobalt 60. All 16 patients subsequently delivered full-term, normal infants. Following delivery, all of the patients had further staging procedures; eight received additional treatment. Subsequently, the disease relapsed in four patients; two eventually died of Hodgkin's disease. The 10-year determinant and overall survival rates were 83% and 71%, respectively. Currently, all offspring are physically and mentally normal, and none has developed a malignancy. Radiotherapy is an appropriate initial treatment for supradiaphragmatic presentations of Hodgkin's disease during the second and third trimesters of pregnancy, provided special attention is paid to treatment and shielding techniques. The outcome for women treated with irradiation for clinical stage I and II Hodgkin's disease during pregnancy has not been shown to be adversely affected by pregnancy, and after the first 8 weeks of gestation, the risk to the fetus appears to be minimal.

Female↗