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M Lazzarino

Publications and source records attributed to M Lazzarino.

At least 55 records · Page 3Linked to original sources
PubMed1999

Mediastinal B-cell lymphoma: a study of its histomorphologic spectrum based on 109 cases.

Mediastinal B-cell lymphoma (MBL) is a distinct variant of aggressive non-Hodgkin's lymphoma with characteristic clinical and biological features but less well-defined histomorphology. We reevaluated 124 biopsy specimens from 109 MBL patients of an Italian/French/German retrospective clinical study. MBL was primarily diagnosed on clinical and histological grounds in conjunction with the detection of CD20 expression by immunohistology. Cytologically, MBL features limited intralesional but considerable interindividual cytological diversity, ranging from medium-sized to very large, atypical cells. Sclerosis and necrosis are restricted to extrathymic and extranodal sites of involvement, predominantly the lung, as is angioinvasion, which predominantly affects larger vessels. The medium-sized and the large cell variants resemble marginal zone lymphoma variants, whereas the very large cell variant of MBL has not so far been found to have any extramediastinal counterpart. We conclude that MBL displays a broad morphological spectrum covering more than is implied by the term "diffuse large cell lymphoma." Because statistical analysis of cytological and histological criteria failed to correlate with prognosis in this comprehensive group of patients, we think it inadvisable further to subclassify MBL.

Humans↗
PubMed1999

Fludarabine, cyclophosphamide, and dexamethasone (FluCyD) combination is effective in pretreated low-grade non-Hodgkin's lymphoma.

PURPOSE: Fludarabine phosphate is effective as a single agent in low-grade non-Hodgkin's lymphoma (NHL). Combined with other antineoplastic agents it enhances the antitumor effect. Our aim was to define the therapeutic efficacy and toxicity of a combination of fludarabine, cyclophosphamide and dexamethasone (FluCyD) in patients with advanced low-grade lymphoma. PATIENTS AND METHODS: Twenty-five adults with pretreated advanced-stage low-grade NHL were treated with three-day courses of fludarabine 25 mg/m2/day, cyclophosphamide 350 mg/m2/day, and dexamethasone 20 mg/day, every four weeks for a maximum of six courses. RESULTS: Of the 25 patients, 18 (72%) responded, 8 (32%) achieving CR and 10 (40%) PR. Seven were failures. The median follow-up was 21 months (5-26). Eight CR patients remain in CR after 5-21 months. Of 10 PR patients, 3 are in continuous PR without further treatment after 12, 17 and 18 months. Myelosuppression was the most prevalent toxic effect. Although severe granulocytopenia (granulocyte count nadir < 500/microliter) and thrombocytopenia (platelet count nadir < 50,000/microliter) occurred in only 10% and 16% of courses, respectively, slow granulocyte or platelet count recovery caused delay of 40% of the courses. Nine patients (36%) required discontinuation of therapy because of persistent granulocytopenia and/or thrombocytopenia: three after one course, three after 2-4 courses, and three after five courses. Thirteen infectious episodes in 11 patients complicated 11% of courses. Two of 10 patients monitored for the circulating EBV load showed increased viral load. One of these developed aggressive lymphoma. CD4+ lymphocytes declined from a pre-therapy median value of 425/microliter to 141/microliter post-treatment (P = 0.001). Non-hematologic toxicities were rare and mild. CONCLUSIONS: The combination of fludarabine with cyclophosphamide and dexamethasone is effective in pretreated advanced-stage low-grade NHL. It may broaden the range of therapeutic options in the salvage treatment of these patients. The main toxicity of this combination is prolonged myelosuppression that may cause treatment delay or withdrawal. The benefit of adding granulocyte colony-stimulating factor, particularly in patients with poor marrow reserve, needs to be investigated.

Adult↗
PubMed1999

The immunosuppression and potential for EBV reactivation of fludarabine combined with cyclophosphamide and dexamethasone in patients with lymphoproliferative disorders.

Fludarabine is effective in chronic lymphocytic leukaemia (CLL) and low-grade non-Hodgkin's lymphoma (NHL). A major side-effect of this purine analogue is immunosuppression which may favour opportunistic infections. Additionally, impairment of immunosurveillance might promote Epstein-Barr virus (EBV) reactivation and possibly favour transformation to high-grade malignancy. The aim of this study was to evaluate the immunosuppression-related effects of the fludarabine-based combination Flucyd in advanced low-grade NHL or CLL by serially monitoring T-lymphocyte subsets, opportunistic infections, EBV-reactivation, and histologic transformation. 24 patients with advanced NHL (n = 21) or CLL (n = 3) received fludarabine 25 mg/m2/d + cyclophosphamide 350 mg/m2/d + dexamethasone 20 mg/d in 3 d courses for a maximum of six courses. The overall response rate was 79% (eight CR, 11 PR, five failures); 11 patients relapsed or progressed between 3 and 19 months from response, and eight are in CR or PR at 3-27 months. The CD4+ lymphocyte counts decreased significantly during therapy from a median of 484/microliter pre-treatment (range 142-1865) to a median of 198/microliter (71-367). In 19 responders monitored off therapy every 3 months until relapse/progression, CD4+ counts were persistently low with minimal recovery over time. During treatment, 16 infections occurred in 11/24 patients. No delayed opportunistic infections occurred in responders while off therapy. The circulating EBV DNA load serially measured in 19 patients by a quantitative PCR assay showed an increase in four patients during treatment. A lymph node biopsy performed in two of these was PCR positive for EBV DNA, whereas LMP1 and EBERs were negative. Six NHL patients evolved into high-grade B-cell NHL. In conclusion, fludarabine combined with cyclophosphamide and dexamethasone is an effective therapy for recurrent indolent lymphoma. This combination produces prolonged T-lymphocytopenia and has the potential to reactivate a latent EBV infection. T-cell dysfunction, however, is not associated with higher incidence of clinical opportunistic infections and does not adversely influence clinical outcome.

Adult↗
PubMed1999

Plateau phase in multiple myeloma: an end-point of conventional-dose chemotherapy.

BACKGROUND AND OBJECTIVE: In multiple myeloma (MM) patients treated with conventional chemotherapy, the attainment and duration of a plateau phase seems to affect survival more than the degree of response to initial treatment. The aims of this study are: 1) to analyze within a cohort of previously untreated MM patients the incidence and the duration of the plateau phase; 2) to correlate it with the presenting features; 3) to assess its impact on survival. DESIGN AND METHODS: A series of 146 consecutive MM patients treated with conventional chemotherapy were evaluated for this study. Of 146 patients, 102 responded (13 achieving complete response, 21 partial response, and 68 minimal response), and 44 showed less than minimal response or a progression. A plateau phase was documented in 115 patients (comprising all responders and 13 non responders. The median plateau phase duration was 21.6 months. The majority of patients received intermittent cycles of chemotherapy (melphalan or interferon) during the plateau phase. In multivariate analysis, lytic lesions, response, and time to the best response (TBR) correlated with the attainment of a plateau, while stage, response as a whole, and TBR showed a significant correlation with the duration. In contrast, the type of response did not correlate with either the attainment or the duration of plateau. To analyze the prognostic impact of presenting features, response to therapy and plateau we used a hierarchical model for survival. The analysis showed that the response to therapy and the duration of plateau significantly affect the survival. INTERPRETATION AND CONCLUSIONS: In multiple myeloma a plateau phase of at least 6 months' duration has a higher impact on survival than the degree of response to conventional chemotherapy so plateau duration could be used as target of therapeutic trials. The best way to maintain the plateau phase remains, however, undefined.

Adult↗
PubMed1998

Serum CA 125 is of clinical value in the staging and follow-up of patients with non-Hodgkin's lymphoma: correlation with tumor parameters and disease activity.

BACKGROUND: CA 125 is a glycoprotein produced by epithelial ovarian tumors and by mesothelial cells; its levels also have been shown to be elevated in patients with non-Hodgkin's lymphoma (NHL). METHODS: The authors evaluated serum CA 125 levels in patients with NHL to elucidate the frequency of this finding, its relationship with other presenting features, and its potential role as tumor marker. One hundred and fifty-seven patients underwent the first CA 125 assessment at onset, 54 at disease recurrence or progression, and 62 during complete remission (CR). RESULTS: Of the 157 patients evaluated at diagnosis (median CA 125: 26 U/mL; range, 2-1400 U/mL), 63 (40%) had increased CA 125 values. Higher CA 125 levels were associated with advanced disease, aggressive histology, mediastinal and/or abdominal involvement, bulky tumor, high tumor burden, effusions, contiguous extranodal extension, high serum lactate dehydrogenase (LDH) activity, and elevated beta2-microglobulin (beta2-M) levels. Parameters identified by multivariate analysis to be independently associated with high CA 125 were: aggressive histology, mediastinal and/or abdominal disease, bulky tumor, high serum LDH activity and beta2-M serum levels, and the presence of effusion (P = 0.0000; explained variation = 0.64). Of the patients presenting with abnormal CA 125 levels, all those who achieved a CR (35) and 3 of the 6 who achieved a partial response had normalization of CA 125 values by the end of treatment. Conversely, CA 125 remained above normal values in 18 nonresponders. All 62 patients evaluated during CR showed normal CA 125 levels. Among patients first evaluated at disease recurrence or progression, 22 of 54 (41%) showed increased CA 125 levels, which were associated with the same parameters of disease found in patients examined at diagnosis. CONCLUSIONS: High serum CA 125 levels were found to correlate with mediastinal and/or abdominal involvement, high tumor mass, and effusions, reflecting the reaction of mesothelial cells to the tumor. Serum CA 125 is a reliable biologic marker for the staging and restaging of patients with lymphoma. Serial measurements are useful, in conjunction with other markers, for monitoring response to treatment.

Adolescent↗
PubMed1998

Multiple myeloma in younger patients: the role of age as prognostic factor.

The presenting features of 356 previously untreated multiple myeloma (MM) patients grouped according to age were analyzed in order (a) to elucidate the possible differences in initial clinical and laboratory features between patients younger than 50 years and the older ones and (b) to statistically assess the prognostic value of the parameters considered, with particular emphasis on the prognostic impact of age. Patients were divided into two groups: group I included 61 patients aged less than 50, group II comprised 295 patients aged 50 or more. No significant differences were found between the two groups in terms of either clinical or laboratory initial characteristics. The treatments adopted and the response to therapy did not differ in the two groups. The prognostic value of presenting features was evaluated for the whole cohort by univariate and multivariate analysis, considering both the observed survival rates and survival rates corrected for the effect of other independent causes of death, using a Poisson model. In both models, calcium level (RR 2.33), performance status (RR 1.83), and creatinine (RR 1.69) maintained their independent negative prognostic value. In contrast, the impact of age was different in the two models. In fact, patients younger than 50 seem to have a better prognosis when the observed survival rates are considered, but they show an increased risk of death when the model takes into account the expected mortality of the underlying population. In conclusion, this study shows that the younger cohort of MM patients has no distinctive initial characteristics with respect to older patients. In multivariate analysis, creatinine levels, calcemia, and performance status show a relevant negative independent prognostic value. Regarding the prognostic impact of age, survival seems to be better among patients younger than 50 than in older patients when the observed survival rates are considered but is significantly worse when the mortality of the corresponding general population, is taken into account.

Adult↗
PubMed1998

All-trans retinoic acid (ATRA) in patients with chronic myeloid leukemia in the chronic phase.

Since in vitro observations indicated that all-trans retinoic acid (ATRA), especially in combination with IFNalpha, can exert significant suppressive effects on Ph+ cells, we investigated the effects and the pharmacokinetic profile of ATRA in a selected cohort of patients with Ph+ chronic myeloid leukemia (CML) in chronic phase. Eighteen patients were treated with ATRA at a dose of 80 mg/m2/day (p.o.), divided into two equal doses after meals, for 7 consecutive days every other week for a maximum of 12 courses (1 course = 1 week on and 1 week off). Pharmacokinetic profiles of ATRA were evaluated during intermittent therapy on days 1 and 7 of course 1; on day 1 of course 2; on day 1 of course 6. Out of the 18 patients treated with ATRA, 11 (61%) went off study before the sixth course of treatment because of progressive hyperleukocytosis (seven cases), or thrombocytosis (one case), or refusal (three cases). Seven (39%) patients completed the first six courses (12 weeks) of treatment with ATRA and two of them (11%) maintained a white blood cell (WBC) <10 x 10[9]/l which was induced by the pretreatment with hydroxyurea. One patient completed the 12th course of ATRA maintaining WBC <10 x 10(9)/l, platelets <500 x 10(9)/l and spleen not palpable. The treatment with ATRA was well tolerated and only one patient discontinued the therapy because of non-hematological side-effects. The area under the concentration-time curve (AUC) decreased significantly (P< 0.001) during the first week of therapy. By adopting an intermittent dosing regimen, 1 week on/ 1 week off (1 course), at the start of courses 2 and 6, we obtained the ATRA AUCs equivalent to the ones achieved on day 1 of course 1. In conclusion, our results showed that ATRA alone appeared to be unable to control the WBC expansion in the CML patients in chronic phase. Moreover, it did not induce any remarkable cytoreductive effects on the platelet count and on the hemoglobin level. The major interest of ATRA would be in combination with other therapies. If ATRA was given in combination with IFNalpha or other agents, dose reduction of these would not be planned. On the basis of the pharmacokinetic profile, ATRA should be administered intermittently rather than continuously.

Adult↗
PubMed1998

Randomized clinical study comparing aggressive chemotherapy with or without G-CSF support for high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia evolving from MDS.

One hundred and five consecutive primary high-risk myelodysplastic syndromes (MDS) or secondary acute myeloid leukaemia (sAML) evolving from MDS (performance status 0-3, ECOG) entered this study. Induction chemotherapy (CT) consisted of idarubicine 12 mg/m2 i.v. on days 1 and 2, etoposide 60 mg/m2/12h i.v. for 5d, Ara-C 120 mg/ m2/12h i.v. for 5d (one or two courses). Patients were randomized to receive or not G-CSF (5 microg/kg/d subcutaneously 48 h after the end of CT). 52 cases underwent CT alone and 53 CT+G-CSF. The CT+ G-CSF patients had a significantly shorter duration of neutropenia (8 nu 16d) with a lower incidence of infections and significantly better responses (CR+PR: 74% v 52%, P<0.05). 40 patients entered CR: 17 with CT and 2 3 with CT+G-CSF. Responders underwent two consolidation courses with the same CT, followed by high-dose Ara-C (2 g/m2 every 12h for 3 d). Most CRs were clonal. At present 21 responders have relapsed (median relapse-free survival 4 5 months). Eight responders received an allo-BMT, six are alive in CR 7-57 months post-transplant. Therefore allo-BMT only increases the chance of a long survival and possible cure. In conclusion, CT+G-CSF did not prolong either CR duration or survival; the growth factor support, however, increased the number of allo-transplantable cases by inducing higher remission rates and improving clinical conditions.

Acute Disease↗
PubMed1998

Efficacy of a combination of idarubicin, etoposide and intermediate-dose cytosine arabinoside as salvage therapy in relapsing or resistant unfavorable lymphoma.

BACKGROUND AND OBJECTIVE: Idarubicin, an anthracycline analogue, is active in non-Hodgkin's lymphoma. This study evaluates the efficacy and toxicity of a combination of idarubicin, etoposide and intermediate-dose cytarabine (IVA) in unfavorable lymphoma in relapse or resistant to prior doxorubicin- or novantrone-based regimens. DESIGN AND METHODS: Thirty patients with relapsing or resistant unfavorable lymphoma received a combination of idarubicin 12 mg/m2 i.v. on day 1, etoposide 60 mg/m2 i.v. every 12 hours for 3 days, and Ara-C 1 g/m2 i.v. every 12 hours for 3 days (3-hour infusion). Median age was 39 years (range: 22-60). All patients had been given prior doxorubicin or novantrone; 54% of them had received 2 or more chemotherapy regimens; 67% of total were in clinical relapse (30% in their second relapse), and 23% had resistant disease. RESULTS: The overall response rate to IVA was 60% (18 of 30 patients). Complete remission rate was 20% (6 of 30) in the whole group, 45% (5 of 11) among patients in their first relapse. Remission median duration was 9 months (range: 1-18), with a 3-year relapse-free and overall survival of 20% and 15%, respectively. Severe neutropenia occurred in 13 patients (43%) and severe thrombocytopenia in 11 patients (37%), with a median duration of 9 and 13 days, respectively. No cardiac toxicity developed; sepsis during neutropenia was documented in four instances and two patients (7%) died of therapy-related events (septic shock). INTERPRETATION AND CONCLUSIONS: Idarubicin combined with etoposide and intermediate-dose cytarabine proved to be an active salvage therapy in unfavorable lymphoma given prior doxorubicin or novantrone; the best results were obtained among patients in their first relapse, with low tumor burden.

Adult↗
PubMed1998

Management of acute promyelocytic leukemia relapse in the ATRA era.

BACKGROUND AND OBJECTIVE: The use of all-trans retinoic acid (ATRA) has changed the natural course of acute promyelocytic leukemia (APL), increasing the percentage of lasting complete remissions. However, management of the few relapses remains undefined. The purpose of the present study was to evaluate the different behavior of APL patients relapsed after induction chemotherapy which had or had not included ATRA. DESIGN AND METHODS: We retrospectively studied 8 patients (3 male and 5 female) who had relapsed after a clinical and molecular complete remission (CR). Five patients relapsed after conventional chemotherapy including anthracyclines, without ATRA which was not available at the onset (group A), 3 relapsed after induction treatment according to AIDA protocol (Idarubicin + ATRA) (group B). Seven patients had both molecular and clinical relapses, 1 (group B) had only a molecular relapse. The median first CR duration was 33 months (range 8-63). To induce a second CR all patients were treated with ATRA 45 mg/m2/day given orally until CR, combined with mitoxantrone 6 mg/m2/day for 6 days and cytarabine 1 g/m2/day for 6 days. RESULTS: Seven out of 8 patients (87.5%) achieved second CR, 1 (group A) did not respond and died within two months. Second CR duration was 21, 43+, 56+, 62+ months in group A and 5, 10, 12+ (with molecular relapse) months in group B. Therefore, only one patient relapsed in group A, while all the group B patients relapsed. INTERPRETATION AND CONCLUSIONS: ATRA combined with chemotherapy is an effective approach to treating APL relapse. It produces a high incidence of second CR with an acceptable toxicity. The duration of the second CR seems, however, to be longer in patients never treated with ATRA before than in patients who relapsed after the AIDA protocol. Therefore, it might be appropriate to adopt more aggressive protocols in this latter subset of patients.

Adolescent↗
PubMed1998

The risk of acute leukemia in patients treated for Hodgkin's disease is significantly higher aft [see bined modality programs than after chemotherapy alone and is correlated with the extent of radiotherapy and type and duration of chemotherapy: a case-control study.

BACKGROUND AND OBJECTIVE: Patients treated for Hodgkin's disease have an increased risk of developing subsequent acute leukemia. This co-operative study was conducted to assess the relative risk associated with several candidate factors including age, splenectomy, combined modality therapy and cumulative drug dose including alkylating agents and nitrosurea derivatives. DESIGN AND METHODS: This study evaluated the risk of acute leukemia according to pretreatment variables and therapy modalities among 1659 patients treated for Hodgkin's disease and followed for a median time of 10 years. Both case-control and actuarial risk studies were performed. Median age was 34 years (range: 12-83); 53% of patients were splenectomized. As to the overall therapy, 348 patients (21%) were given radiotherapy (RT) alone, 375 (23%) chemotherapy (CT) alone (including MOPP, MOPP + ABVD or MOPP + ABVD + lomustine); 936 (56%) received both CT and RT, either as primary or salvage treatment. RESULTS: The overall 15-year actuarial risk of leukemia was 4.2%; the hazard function curve showed two peaks of risk at the 3th and the 8th year from the initiation of therapy and no leukemia beyond the 12th year of follow-up. Risk of leukemia was 0.3% after RT alone, 2.8% after CT alone (2.2% after MOPP; 4.4% after MOPP + ABVD + lomustine), and 5.4% in patients given combined modality therapy (10.2% for RT + MOPP; 15.6% for RT + MOPP + lomustine). No leukemia occurred after ABVD alone and the risk was low (0.6%) when neither mechlorethamine nor lomustine were utilized. Patients who had received extended radiotherapy including abdomen and pelvis in addition to MOPP showed a significantly higher risk of leukemia compared to those given limited RT + MOPP (P = 0.01). Case-control analysis indicated advanced stage, type and duration (> 8 months) of CT and extension of RT as significant risk factors for leukemia. Compared to RT alone, the odds ratio was 5.9 after MOPP + extended RT, and 8 when a lomustine-containing regimen was used, as well. Neither age nor splenectomy were independent risk factors for leukemia; splenectomy was influential only when patients had been given MOPP chemotherapy, as well. INTERPRETATIONS AND CONCLUSIONS: Both case-control and actuarial analyses indicated that: a) combined modality therapy with MOPP and extensive RT (including abdomen and pelvis), and the use of lomustine added to the leukemogenic risk of MOPP alone; b) programs without mechlorethamine, procarbazine and lomustine were almost devoid of leukemogenic risk.

Abdomen↗
PubMed1997

Treatment with recombinant human erythropoietin (rHuEpo) in a patient with paroxysmal nocturnal haemoglobinuria: evaluation of membrane proteins CD55 and CD59 with cytofluorometric assay.

We describe a 28-year-old man with paroxysmal nocturnal haemoglobinuria (PNH) and a high transfusion requirement. Prior to and during therapy with recombinant human erythropoietin (rHuEpo), we evaluated the levels of 'decay-accelerating-factor', CD55, and 'membrane-inhibitor-of-reactive-lysis', CD59, as markers of the disease, whilst CD58, a marker present on leucocytes, was utilized to monitor normal haemopoietic activity. The patient became transfusion independent 1 month after beginning rHuEpo and remains well. The analysis of CD55, CD59 and CD58 suggests that the efficacy of rHuEpo was due to a selective rHuEpo action on normal erythroid clones.

Adult↗
PubMed1997

Treatment outcome and prognostic factors for primary mediastinal (thymic) B-cell lymphoma: a multicenter study of 106 patients.

PURPOSE: To define clinicopathologic features, response to treatment, and prognostic factors of primary mediastinal B-cell lymphoma (MBL), a CD20+ tumor recognized as a distinct entity among non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: One hundred six patients presented with disease confined to thorax (86%), bulky mediastinum (73%), superior vena cava syndrome (47%), and contiguous infiltration (57%). Ninety-nine received doxorubicin-containing chemotherapy (CHT). RESULTS: Thirty-five of 99 patients were primarily CHT-resistant, and 64 responded: 23 achieved complete response (CR) and 41 achieved response with residual mediastinal abnormality. Seventy-seven percent of responders received mediastinal radiotherapy (RT). Of 64 responders, 18 (28%) relapsed: none of 23 CR patients and 18 of 41 (44%) with residual mediastinal abnormality. Relapse-free survival rate of responders was 71% at 3 years. Actuarial 3-year survival rate was 52% for all patients and 82% for responders. Predictive factors of poor outcome were identified by logistic regression; Cox survival analysis was performed on death and relapse. Pericardial effusion (P < .001) and Eastern Cooperative Oncology Group (ECOG) performance status > or = 2 (P = .009) predicted nonresponse (NR) and affected survival. Less than partial midway response to CHT predicted NR to subsequent therapies. Bulky disease was related to persistent mediastinal abnormality and risk of relapse (P = .025). CONCLUSION: MBL is an aggressive NHL with unique clinicopathologic aspects, often refractory to current CHT designed for high-grade NHL. Poor performance status and pericardial effusion predict NR and poor survival. Inadequate response after the first courses of front-line CHT predicts failure of subsequent treatment. Responders with bulky mediastinum or residual mediastinal abnormality after CHT are at risk of relapse. These factors should help to select high-risk patients for intensive treatments.

Adolescent↗
PubMed1997

Clinical pharmacokinetics of tretinoin.

Recent reports of the dramatic antitumour effect of tretinoin (all-trans retinoic acid) in patients with acute promyelocytic leukaemia (APL) have generated a great deal of interest in the use of this drug as a chemopreventive and therapeutic agent. However, the biological efficacy of tretinoin is greatly impaired by (presumably) an induced hypercatabolism of the drug leading to reduced tretinoin sensitivity and resistance. Several pharmacokinetic studies have shown that plasma drug exposure [as measured by the plasma area under the concentration-time curve (AUC infinity)] declines substantially and rapidly when the drug is administered in a long term daily tretinoin regimen. These observations led to the hypothesis that the rapid development of acquired clinical resistance to tretinoin may have a pharmacological basis and result from an inability to present an effective drug concentration to the leukaemic cells during continuous treatment. The principal mechanisms proposed to explain the increased disappearance of tretinoin from plasma include: (i) decreased intestinal absorption; (ii) enhanced enzymatic catabolism; and (iii) the induction of cytoplasmic retinoic acid binding proteins (CRABP), which leads to increased drug sequestration. The most favoured explanation is that continuous tretinoin treatment acts to induce drug catabolism by cytochrome P450 (CYP) enzymes. Several strategies aimed at preventing or overcoming induced tretinoin resistance have been, and are being, planned. These strategies include intermittent dose administration, administration of pharmacological inhibitors of CYP oxidative enzymes, combination with interferon-alpha and intravenous administration of liposome-encapsulated tretinoin. As these strategies are now under investigation and the number of patients enrolled is small, further studies are needed to determine the efficacy and toxicity of these new schedules of drug administration. In this article we provide an overview of the relevant aspects of tretinoin physiology and pharmacokinetics, and summarise the current status of knowledge to help in the better optimisation of tretinoin administration.

Antineoplastic Agents↗
PubMed1997

Nodular lymphocyte predominance Hodgkin's disease: long-term observation reveals a continuous pattern of recurrence.

We evaluated the presenting clinical characteristics and outcome of 68 patients with nodular lymphocyte predominance Hodgkin's disease (NLP-HD), in order to delineate the pattern of evolution of the disease. The male to female ratio was 46/22 and median age 35 yrs (range, 14-86). Eight patients had a history of benign hyperplasia on lymph node biopsies performed 6 to 36 months before the diagnosis of NLP-HD. Early stage disease accounted for 75% of cases. One patient had a coexistent non-Hodgkin's lymphoma (NHL). Treatment was as follows: radiotherapy in 26, chemotherapy in 23, combined modality in 19. CR rate was 93% (63/68). 18 patients relapsed as HD and 5 developed NHL. The cumulative risk of NHL was 9% at 10 yrs. During remission, 4 patients had 5 episodes of follicular hyperplasia histologically documented. Overall survival rate was 71% at 10 yrs and and 63% at 15 yrs. Freedom from progression (FFP) declined from 67% at 5 yrs to 45% at 10 yrs, because of late relapses. Localized disease predicted for a better FFP (p = 0.01), but was not associated with a reduced risk of recurrence over time. NLP-HD is characterized by an indolent course with a constant pattern of relapse over time, also in patients with early stage disease at diagnosis. In addition to relapse as NLP-HD, patients may evolve into a NHL or develop benign lymph nodal hyperplasia. Careful long-term follow up is needed for these patients.

Adolescent↗
PubMed1997

Primary mediastinal B-cell lymphoma: update of its clinicopathologic features.

The peculiar clinical, histomorphological and biological characteristics of PMBCL are reviewed. Special emphasis is given to the frequent aggressive clinical behaviour of this lymphoma in which conventional prognostic factors seem inadequate to identify high risk cases. The need for new clinical and/or biological prognostic markers is stressed.

Biomarkers, Tumor↗