Prevalence of the colonization of Helicobacter pylori among students of the school of dentistry, University of Granada, Spain.

BACKGROUND: The oral cavity is a reservoir for Helicobacter pylori, and occupations that involve close contact with it, like Dentistry, could entail a higher risk of colonization. The aim of this study was to evaluate if the length of stay at the School of Dentistry of the University of Granada could influence colonization by H. pylori, , and to furthermore correlate colonization by H. pylori, with the state of oral health and oral hygiene habits. MATERIAL AND METHODS: The study groups were: Group 1, 35 students of Odontology in their first year of studies; Group 2, the same 35 students when they were in their fifth academic year; Group 3, 35 students from University study programs unrelated with Health and of the same age as the group 2 students. All underwent H. pylori, colonization determinations by means of the urea breath test (UBT), stool antigen test and a serological test. Also studied were the variables plaque index, gingival index and the number of times teeth were brushed per day. The Student t test was used for comparisons among the three studied groups. The Chi-squared test and Pearson correlation coefficient were used to determine any connection between colonization by H. pylori, and the variables studied. RESULTS: Comparisons between groups 1 and 2 and between groups 2 and 3 showed significant differences regarding colonization by H. pylori, plaque index, gingival bleeding index and tooth brushing. A positive correlation was found between being colonized by H. pylori, and having a gingival index higher than 10% and tooth brushing once a day or less, in all the studied groups. CONCLUSIONS: Colonization by H. pylori, among Dentistry students at the University of Granada decreased over a four-year time period at the University. Factors related with better oral health, such as a lower gingival index and more frequent tooth brushings, would explain these results.

Serologic control against hepatitis B virus among dental students of the University of Granada, Spain.

BACKGROUND: To evaluate the immunological situation against hepatitis B virus (HBV) of a cohort of dentistry students, to analyze the behavior of the levels of hepatitis B surface antigen (anti-HBs) after the administration of one or three vaccine doses, and to determine the influence of age and sex on the immune response. MATERIAL AND METHODS: This retrospective cohort study included students attending the School of Dentistry of the institution where the study was performed from 2005 to 2012 who had completed the public health vaccination calendar for HBV at the age of 12-13. Data on age, sex, basal anti-HBs levels, post-vaccination anti-HBs results and final anti-HBs levels were collected. Comparisons of the basal and final levels, as well as associations regarding age and sex, were performed by means of the Student t and Chi-square tests. RESULTS: Of the 359 students, 97 (27.02%) had basal antibody concentrations <10 mIU/ml, whereas in 262 the levels of anti-HBs were ≥10 mIU/ml (72.98%). Of the 288 participating students who completed the School's protocol for immunization, 287 (99.65%) attained a level of protection ≥10 mIU/ml. Globally, there were statistically significant differences between the basal antibody levels and those achieved after administration of the vaccine and booster, but no association with age or sex was observed. CONCLUSIONS: About 70% of dental students vaccinated as pre-adolescents had serologic evidence of protection against HBV. Administering a booster is associated with the presence of an excellent immune memory. There is clearly a need to reinforce control of the antibody levels in groups at risk, such as Dentistry students.

Rituximab Chimeric Anti-CD20 Monoclonal Antibody Therapy for Relapsed Indolent Lymphoma: Half of Patients Respond to a Four-Dose Treatment Program.

PURPOSE: The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. PATIENTS AND METHODS: This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. RESULTS: From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. CONCLUSION: The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.

Prospective trial of targeted radioimmunotherapy with Y-90 ibritumomab tiuxetan (Zevalin) for front-line treatment of early-stage extranodal indolent ocular adnexal lymphoma.

BACKGROUND: To determine the efficacy and side-effects of (90)Y ibritumomab tiuxetan (Zevalin) as front-line treatment in patients with early-stage extranodal indolent lymphoma of the ocular adnexa (orbit, conjunctiva, or eyelid). PATIENTS AND METHODS: From August 2004 to November 2007, 12 patients with stages I-E extranodal indolent lymphoma of the ocular adnexa were enrolled in a prospective trial of rituximab followed by (90)Y ibritumomab tiuxetan (Zevalin therapeutic regimen). For each patient, clinical examinations and imaging studies were used to document response to therapy using the The International Working Group response criteria. All patients had (111)In ibritumomab tixuetan imaging to confirm expected biodistribution before (90)Y-Zevalin therapy; in addition, three patients had an optional single photon emission computed tomography-computed tomography scan to estimate the absorbed radiation dose to the orbital and ocular tissues. RESULTS: The study included seven women and five men. The median age was 60 years (range 22-79). Nine patients had mucosa-associated lymphoid tissue lymphoma of conjunctiva or orbit; three patients had grades 1-2 follicular lymphoma of orbit. One patient who had been deemed stage I-E initially was found to have another lesion in her deltoid muscle on positron emission tomography 2 weeks after enrollment. She was kept on trial although her disease was reclassified as stage IV due to this single additional (biopsy-proven) site. Ten patients had a complete response and two partial response (PR) within 3 months of treatment. One patient had a recurrence in the upper eyelid 6 months after an initial PR; he then received 30 Gy of external-beam radiotherapy (EBRT). His disease later progressed again in the orbit and he is currently being considered for other treatments. A second patient who attained a PR has remained stable with no progression 12 months after treatment. With a median follow-up time of 20 months (range 6-44 months), there were no cases of distant (extraorbital) relapse. All 12 patients experienced grade I or II transient pancytopenia during the first 3 months after enrollment in the trial. There were no episodes of grade III or IV myelosuppression. The estimated absorbed radiation dose to the orbital soft tissues was <3 Gy, 10 times lower than that with EBRT. CONCLUSIONS: Rituximab followed by (90)Y ibritumomab tiuxetan is an effective and safe front-line treatment for early-stage extranodal indolent B-cell lymphoma of the ocular adnexa.

Detection of minimal residual cells carrying the t(14;18) by DNA sequence amplification.

By means of the polymerase chain reaction (PCR) technique, DNA sequences were amplified that flank the crossover sites of a characteristic chromosomal translocation for follicular lymphomas, t(14;18)(q32;q21). This technique permitted the detection of cells carrying the t(14;18) hybrid DNA sequences at a dilution of 1:100,000. The remission marrow and blood samples of a patient with follicular lymphoma and the t(14;18) failed to show any abnormality by morphological examination and conventional Southern blot analysis. However, the t(14;18) hybrid DNA sequences were detected by the PCR technique. Thus, this technique is a highly sensitive tool to detect minimal residual cells carrying the t(14;18) and has the potential to identify a subpopulation of patients with subclinical disease.

The addition of rituximab to CHOP chemotherapy improves overall and failure-free survival for follicular grade 3 lymphoma.

BACKGROUND: The benefit of adding rituximab to anthracycline-based therapy for follicular lymphoma grade 3 has not been studied. PATIENTS AND METHODS: We retrospectively reviewed the records of 45 patients with follicular grade 3 lymphoma who were treated with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) at The University of Texas MD Anderson Cancer Center. Response rate, failure-free survival (FFS), and overall survival (OS) were estimated and a historical comparison to CHOP-only-treated patients was made. RESULTS: The International Prognostic Index (IPI) distribution was 47% low, 36% low intermediate, 13% high intermediate, and 4% high risk. The complete response rate was 96%. Forty-four of 45 patients are still alive. Median follow-up for the alive patients is 3.5 years. The 3-year FFS rate according to the IPI was 80% [95% confidence interval (CI) 64% to 100%] in low, 81% in low intermediate (95% CI 64% to 100%), and 50% (95% CI 25% to 100%) in high-intermediate/high-risk patient group. The addition of rituximab to CHOP improved both 5-year FFS, 71% (95% CI 58% to 87%) compared with 44% (95% CI 36% to 55%) with P value of 0.019, and 5-year OS, 98% (95% CI 93% to 100%) compared with 75% (95% CI 67% to 84%) with P value of 0.0034. CONCLUSION: The addition of rituximab to CHOP provided a high response rate and excellent early survival. Poor-risk patients continue to demonstrate a high rate of failure despite the use of rituximab.

A phase I/II trial of pixantrone (BBR2778), methylprednisolone, cisplatin, and cytosine arabinoside (PSHAP) in relapsed/refractory aggressive non-Hodgkin's lymphoma.

The purpose of the study was to evaluate the safety, efficacy, and pharmacokinetics of pixantrone (BBR2778) when substituted for etoposide in the ESHAP regimen in patients with aggressive relapsed or refractory non-Hodgkin's lymphoma. Nineteen patients received protocol therapy, consisting of pixantrone 80 mg/m2 over 1 h on day 1, methylprednisolone 500 mg on days 1 - 5, cisplatin 25 mg/m2 on days 1 - 4, and cytarabine 2000 mg/m2 on day 5. Cycles were repeated every 21 days, in the outpatient setting. Dose limiting toxicity, consisting of bone marrow suppression, occurred at the first dose level (80 mg/m2), which was defined as the recommended dose. Grade 3 and 4 toxicities were mainly hematologic. Only one patient had grade 4 febrile neutropenia. No significant decreases in ejection fraction greater than 20% occurred. Overall response rate was 58%, with 37% complete and 21% partial responses. Six of the 11 responders (55%) underwent stem cell transplant. Median time to progression and overall median survival were 5.7 months and 14.5 months, respectively. There is no significant interaction between pixantrone and the combined drugs. The recommended dose of pixantrone in combination with methylprednisolone, cytarabine, and cisplatin (PSHAP) is 80 mg/m2. PSHAP is an active salvage regimen and should be further evaluated as a pretransplant cytoreductive regimen.

Chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin for parenchymal brain lymphoma.

Ten patients with parenchymal CNS lymphoma received combination chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin (DHAP), and additional therapy according to clinical circumstances. Two of four patients with primary CNS lymphoma achieved and remain in complete remission (CR). Four of six patients with CNS lymphoma at relapse also achieved CR. DHAP is active against CNS lymphoma. Further trials with DHAP, particularly in conjunction with other treatment modalities, are warranted.

Serum interleukin 6 levels are elevated in lymphoma patients and correlate with survival in advanced Hodgkin's disease and with B symptoms.

Several cytokines including gamma-interferon, tumor necrosis factor alpha, interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) are pyrogenic and can inhibit lipogenic processes. Because patients with lymphoma often suffer from fever, weight loss, and night sweats (B symptoms), the etiology of which is unknown, the authors investigated serum levels of these cytokines in normal volunteers and in patients with Hodgkin's and non-Hodgkin's lymphoma. Sixty serum samples from patients with Hodgkin's disease (28 patients) or non-Hodgkin's lymphoma (32 patients), as well as 20 samples from normal volunteers, were collected. The majority of patients had advanced (Stage III or IV) or relapsed disease. The assay for gamma-interferon was a specific and sensitive radioimmunoassay (lower limit of detection = 0.1 unit/ml); the assays for tumor necrosis factor alpha, IL-1 beta, and IL-6 were enzyme-linked immunoassays with lower limits of sensitivity of 10 pg/ml, 20 pg/ml, and 22 pg/ml, respectively. There were no statistically significant differences in gamma-interferon, tumor necrosis factor alpha, or IL-1 beta levels between lymphoma patients and normal subjects. In contrast, 20 of 57 patients (35%) with lymphoma as compared with 0 of 19 normal volunteers (0%) had detectable serum IL-6 levels (P < 0.005, chi 2 test). Interestingly, 17 of 29 lymphoma patients with B symptoms (59%) as opposed to 3 of 28 lymphoma patients without B symptoms (11%) had detectable serum IL-6 levels (P < 0.001, chi 2 test); the median IL-6 level was 28.9 pg/ml (B symptoms present) versus undetectable (no B symptoms) (P < 0.005, Mann-Whitney U test). Analyzing Hodgkin's and non-Hodgkin's lymphoma groups separately revealed similar results. IL-6 levels showed no significant correlation with time from diagnosis, beta 2-microglobulin, or lactate dehydrogenase levels. However, analysis by the method of Kaplan and Meir demonstrated that the median survival of Hodgkin's disease patients with detectable IL-6 levels (> or = 22 pg/ml) was 10 mo, whereas the median survival has not been reached at a median follow-up time of 37.5 mo in those patients with lower values (Wilcoxon P value = 0.0012). There were too few patients in each subset of non-Hodgkin's lymphoma to determine the correlation between IL-6 and survival but, considered as a single group, a statistically significant correlation was not found.(ABSTRACT TRUNCATED AT 400 WORDS)

Nucleic acid flow cytometry in large cell lymphoma.

Between 1978 and 1985, 140 patients with large cell lymphoma (27 follicular, 92 diffuse, 5 immunoblastic, and 16 transformed) had DNA-RNA cytometry performed on involved tissue. DNA-RNA features were correlated with treatment outcome and compared to other established prognostic factors in 63 newly diagnosed patients who received uniformly intensive therapy. Significantly better outcome was noted for previously untreated patients with intermediate RNA content (RNA index, 1.0-1.8), diploid DNA content, and (during the initial 12-month follow-up) low proliferative activity. Of patients followed beyond 12-24 months, those with high proliferative activity appeared to have the most durable remissions, although this was not statistically significant. These findings suggested a preferential impact of intensive chemotherapy on patients with intermediate RNA content and possibly those with high proliferative activity, since previous studies and our own experience with relapsing patients have indicated a progressively worse outlook with higher proliferative activity and RNA index values. In newly diagnosed patients, multivariate analysis identified RNA content as the most important prognostic factor, followed by proliferative activity and serum lactate dehydrogenase. Thus, for patients with large cell lymphoma, DNA-RNA cytometry appears to be a valuable prognostic parameter for identifying a subset of patients who have a high likelihood of cure with intensive chemotherapy.

Frequent nonrandom chromosome abnormalities in 27 patients with untreated large cell lymphoma and immunoblastic lymphoma.

Fresh tumor samples from 27 patients with large cell lymphoma, either previously untreated (26 patients) or minimally treated (one patient), were processed for cytogenetic studies. Cytogenetic abnormalities were observed in all patients, most commonly in chromosomes 1, 3, 7, 12, 14, 17, and 18. Nine chromosomal breakpoints appeared frequently: 14q32 in 14 instances; 18q21 in seven; 9p13-21, 17p11-13, and 3q21-23 in six each; 1p11-21 in five instances; 1p36 in four; and 2p21-23 in three. The most common structural abnormalities were t(14;18)(q32;q21) in seven patients (26%) and 17p- in six (22%). The presence of 17p- was associated with a significantly higher proliferative capacity as manifested by the percentage of S phase = 22% versus 11% for cases without 17p-(P less than 0.05). Trisomy 12, typical of small lymphocytic lymphoma, was seen in five patients in this series, all of whom had diffuse large cell lymphoma; frequently, it appeared simultaneously with t(14;18). The two patients with immunoblastic lymphoma of B-cell type had an abnormality involving chromosome 2p21-23. Deletions in the long arm of chromosome 6, previously described as typical of diffuse large cell lymphoma and B-cell immunoblastic lymphoma were observed infrequently in this series. However, this abnormality has been present in 50% of patients with large cell lymphoma previously exposed to therapy, suggesting that it may be related to effects of chemotherapy or to clonal evolution.

Expression of CD26 and its associated dipeptidyl peptidase IV enzyme activity enhances sensitivity to doxorubicin-induced cell cycle arrest at the G(2)/M checkpoint.

CD26, a M(r) 110,000 surface-bound ectopeptidase with dipeptidyl peptidase IV (DPPIV) activity, has an array of diverse functional properties, with a role in T-cell physiology and the development of certain human cancers. In this study, we report that surface expression of CD26, through its associated DPPIV enzyme activity, enhanced sensitivity of Jurkat T-cell transfectants to G(2)-M arrest induced by the chemotherapeutic drug, doxorubicin. This was associated with disruption of cell cycle-related events, including hyperphosphorylation and inhibition of p34(cdc2) kinase activity, phosphorylation of cdc25C, and alteration in cyclin B1 expression. In addition, we demonstrate that the addition of exogenous soluble DPPIV enhanced sensitivity of lymphoid tumor cell lines to doxorubicin, suggesting a potentially useful clinical role for CD26/DPPIV in the treatment of selected human hematological malignancies.

Long-term follow-up with ABDIC salvage chemotherapy of MOPP-resistant Hodgkin's disease.

Thirty-six consecutive patients with advanced recurrent Hodgkin's disease resistant to chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) were treated with doxorubicin (Adriamycin), bleomycin, (dacarbazine) DTIC, (lomustine) CCNU, and prednisone (ABDIC). Among the 34 patients evaluable for response, complete remission occurred in 35% and partial remission in 35%. The achievement of complete remission during primary MOPP induction was a statistically significant prognostic factor that predicted complete remission with ABDIC (p less than 0.01). The median time to complete remission was 2 months (range 1-11 mo). The median relapse-free survival time for complete responders is 47 months, and an estimated 53% of all patients who achieve complete remission are projected to be alive, free of disease off therapy at 3 years from initiation of ABDIC. The median survival of all patients is 24 months. The median survival of complete responders, partial responders, and nonresponders is 70, 17, and 4 months, respectively. The survival curve for complete responders is significantly different from that for partial responders (p less than 0.01); the survival curve for partial responders is also significantly different from that of nonresponders (p less than 0.01). Toxicity of ABDIC was acceptable; only one patient died from complications of myelosuppression. Our results indicate that ABDIC is a potentially curative regimen for a fraction of patients with MOPP-resistant Hodgkin's disease who achieve complete remission with prior MOPP therapy. It also prolongs the survival of patients who do not achieve complete remission with prior MOPP therapy.

Serum interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma.

PURPOSE: Interleukin-6 (IL-6) is a potent immunomodulatory cytokine that may have pathogenetic and prognostic significance in a number of disorders. The objective of this study was to examine the correlation between serum IL-6 levels and phenotypic characteristics, as well as outcome of patients with diffuse large-cell lymphoma (DLCL). PATIENTS AND METHODS: Using an enzyme-linked immunosorbent assay (ELISA; lower limit of sensitivity, 0.35 pg/mL), we measured IL-6 levels in frozen sera from 33 healthy controls and 58 untreated patients with DLCL who were enrolled onto a single combination chemotherapy protocol. Serum IL-6 levels were correlated with clinical and laboratory features at diagnosis and with failure-free and overall survival. RESULTS: Serum IL-6 levels in the lymphoma patients (median, 4.37 pg/mL; range, < 0.35 to 110 pg/mL) were significantly higher than in the control group (median, < 0.35 pg/mL; range, < 0.35 to 1.87 pg/mL) (P < .0001). Serum IL-6 levels were higher in patients with B symptoms (P = .012), an elevated beta 2-microglobulin level (> or = 3.0 mg/L) (P = .017), and a poor performance status (P = .02). Direct linear correlations with the erythrocyte sedimentation rate (ESR), platelet count, and total WBC count, and an inverse linear correlation with the serum albumin level, were observed (all P < .02). Patients with elevated serum IL-6 levels had inferior failure-free (P = .042) and overall survival (P = .05) compared with those with normal serum IL-6 levels. CONCLUSION: In patients with DLCL, elevated serum levels of IL-6 at diagnosis are frequent, strongly associated with many adverse disease features, and predictive of a poor failure-free and overall survival.

A 10-year update of CHOP-Bleo in the treatment of diffuse large-cell lymphoma.

Long-term follow-up results of two studies using cyclophosphamide, doxorubicin, vincristine, and prednisone plus bleomycin (CHOP-Bleo) for the treatment of diffuse large-cell lymphoma are presented. Twenty-eight patients were treated with conventional-dose CHOP-Bleo and 36 patients with maximally tolerated doses of CHOP-Bleo. The maximal duration of follow-up was 10.5 years. The minimum follow-up was 5.7 years. Seventy-five percent of the conventional-dose group achieved a complete remission (CR) with a 10-year actuarial survival of 53% and a corresponding relapse-free survival (RFS) of 69% for CRs. Eighty-one percent of the high-dose group achieved CR, and the 10-year actuarial survival for all patients and RFS for CRs were 48% and 63%, respectively. The combined actuarial survival and RFS for both groups were 51% and 66%, respectively, at 10 years. For 11 patients with stage III disease, 91% achieved CR, 52% survived at 10 years, and the RFS was 67% for CRs. Seventy-five percent of 44 patients with stage IV disease achieved CR, 50% survived at 10 years, and the RFS was 67% for CRs. Three of the 16 relapses occurred late, between 30 to 65 months after initiation of therapy. Neuropathy occurred in 14 patients (22%). Five patients (8%) died of complications related to treatment. Five (8%) had clinically apparent, but nonfatal cardiopulmonary complications. The CHOP-Bleo regimen is an effective treatment for diffuse large-cell lymphoma, and is moderately well tolerated. The use of high-dose CHOP-Bleo for induction therapy did not result in any advantage after long-term follow-up.

Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma.

Based on remarkable activity in refractory lymphomas, a combination of etoposide, cisplatin (both administered by 4-day continuous infusions), cytarabine (Ara-C), and dexamethasone (EDAP) was evaluated in 20 patients with advanced myeloma refractory to standard melphalan and prednisone (MP) and/or vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dexamethasone (VAD) and even to high doses of melphalan (HDM) (seven patients). Forty percent of patients responded regardless of previously recognized risk factors (eg, duration of drug resistance, tumor mass, and serum lactic dehydrogenase [LDH] level). While the median survival was only 4.5 months, patients with good performance (Zubrod less than 2) and low or intermediate tumor stage survived more than 14 months compared with only 2 months for the remaining group. EDAP could be readily administered in the outpatient clinic, but neutropenic fever prompted hospital admission in 80% of patients, half of whom developed penumonia and sepsis, a fatal outcome in four patients. Severe myelosuppression was of short duration, so that subsequent cycles could be administered every 3 to 4 weeks. No serious extramedullary toxicity, including renal toxicity, was encountered. Marrow toxicity and hence infectious complications may be reduced by elimination of Ara-C without compromising treatment efficacy. We conclude that the lack of cross-resistance with VAD and even HDM makes EDAP or a similar combination an attractive regiment to be formally explored in an alternating sequence with VAD in high-risk myeloma.

MIME chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide) as treatment for recurrent Hodgkin's disease.

Forty-seven patients with Hodgkin's disease in relapse were treated with MIME combination chemotherapy (methyl-GAG, ifosfamide, methotrexate, etoposide). All patients had previously received nitrogen mustard, vincristine, prednisone, procarbazine (MOPP) or similar regimens and doxorubicin-containing combinations, and many had received extensive irradiation. Complete remission (CR) occurred in 23%, and was influenced by presence of extranodal disease, hemoglobin, lactic dehydrogenase (LDH), and number of prior relapses. Median survival for all patients was 50 weeks, and was affected adversely by the presence of extranodal disease and the number of prior relapses. Toxicity was significant, including infections (23%), neutropenic fever (34%), and hemorrhagic cystitis (23%), but was related in part to the extent of prior therapy. These results with this novel chemotherapy program in heavily pretreated patients suggest that MIME should be studied in less extensively treated patients and considered as a part of treatment programs for patients with Hodgkin's disease in first relapse.

Results of MIME salvage regimen for recurrent or refractory lymphoma.

Based on encouraging results of two previous ifosfamide-VP-16 salvage combinations, methyl-gag was added to ifosfamide, methotrexate, and etoposide (VP-16). This combination is called MIME. A total of 208 patients with recurrent lymphoma were treated with this regimen. Response rates were 24% for complete remission and 36% for partial remission. The MIME regimen was more effective in patients who were treated after being off front-line therapy for longer than 6 months. However, responses were also seen in patients with disease clearly resistant to front-line therapy, suggesting that MIME was at least partially non-cross-resistant with front-line doxorubicin-containing regimens. The 15-month median relapse-free survival of complete responders and the 9-month overall median survival time for all patients treated were both similar to results from previous ifosfamide-VP-16 combination use. This regimen has been effective in the treatment of patients with recurrent or refractory lymphoma, but cannot be considered curative in the majority of cases.

Mantle cell lymphoma: correlation of clinical outcome and biologic features with three histologic variants.

PURPOSE: Clinical data and histologic material were retrospectively analyzed in 46 cases of previously untreated mantle cell lymphoma (MCL) to more fully characterize the clinical response pattern of these lymphomas and to determine whether growth pattern significantly affected clinical outcome. MATERIALS AND METHODS: The histologic pattern was classified as diffuse (61%), nodular (13%), and mantle zone (26%) in accordance with stated criteria. RESULTS: Bone marrow infiltration was detected in 69% of cases; the frequency of involvement correlated with histologic pattern, being most common in diffuse variants and least common in mantle zone variants. Other sites of extranodal involvement were observed in 50% of cases. Cyclin-D1 staining revealed nuclear positivity in 23 of 25 patients (92%) and no difference was observed between the various histologic patterns. Rearrangement at the bcl-1 major translocation cluster (MTC) was detected in seven of 21 cases, without regard for histologic pattern. Complete response rates to doxorubicin-based regimens showed a striking correlation with histologic pattern. Seventy-three percent of patients with a mantle zone pattern attained a complete response compared with only 25% of patients with a nodular pattern and 19% with a diffuse pattern. Three-year survival rates were 100%, 50%, and 55% for patients with mantle zone, nodular, and diffuse histologic patterns, respectively. CONCLUSION: We conclude that (1) diffuse and nodular MCL are associated with a poor treatment response and a poor overall survival rate; (2) the mantle zone variant exhibits the clinical attributes of a low-grade lymphoma; and (3) the poor survival rates of patients with nodular and diffuse MCL suggest that these variants be classified as intermediate-grade lymphomas. However, the trend of the time to treatment failure curve does not indicate that current regimens can cure MCL.

High-dose cytosine arabinoside in non-Hodgkin's lymphoma.

Thirty-two patients with refractory non-Hodgkin's lymphoma were treated with high-dose cytosine arabinoside (ara-C) given at 2 g/m2 IV over three hours every 12 hours for 4-8 g/m2/course repeated at three to four week intervals. There were eight partial responses (29%) and two minor responses among 28 evaluable patients. The median response duration was 10 weeks (range, 6-33 weeks). The median survival was significantly prolonged in responders compared to nonresponders (28 versus 15 weeks; p = 0.03). Two additional patients treated with 12 g/m2/course died of sepsis and myelosuppression. The dose-limiting toxicity was myelosuppression, which was more pronounced in patients with prior extensive radiation therapy and bone marrow involvement. In vivo measurements of intracellular concentrations of ara-CTP, the active metabolite of ara-C, showed significantly higher values in bone marrows with lymphomatous involvement compared to normal bone marrows (210 versus 95 microM; p = 0.05), probably indicating a preferential formation and retention of ara-CTP in malignant cells compared to normal hemopoietic cells. In addition, higher ara-CTP levels were found in bone marrows that had higher percentages of cells in S phase.