Population-based incidence of lymphomas in the French Nord-Pas-de-Calais region between 2001 and 2005: Annual estimations and spatial analysis.

BACKGROUND: Non-Hodgkin's lymphomas (NHL) are the seventh most commonly diagnosed cancer in France. Nord-Pas-de-Calais is ranked as the region with the highest incidence of cancers and deaths by cancer in France. With its rich industrial past and its contrasted population densities between urban and rural territories, Nord-Pas-de-Calais represents a geographic area of interest to study the overall incidence of NHL and examine spatial variation of NHL incidence between the 170 cantons of the region. METHODS: LYMPHONOR was a population-based multicentre retrospective study of patients residing in the Nord-Pas-de-Calais region and diagnosed with NHL between January 2001 and December 2005. Spatial distribution of NHL incidence in Nord-Pas-de-Calais was explored using two complementary approaches: adjusted smoothed standardised incidence ratio (SIR) and spatial scan statistics (detection of atypical clusters). RESULTS: Between 2001 and 2005, 2132 new cases of NHL were diagnosed in the Nord-Pas-de-Calais region. In 2005, age-standardised NHL incidence rates were 10.2 and 7.0 cases per 100,000 person-years in male and female residents, respectively. No significant spatial disparities in NHL incidence were found within the Nord-Pas-de-Calais region. The age-adjusted smoothed SIR varied from 0.82 to 1.25 between cantons. Consistently, spatial scan statistics did not detect any significant atypical cluster of high NHL incidence. CONCLUSION: Comparison with national data collected during the same period does not show an overincidence of NHL in the Nord-Pas-de-Calais region. In addition, no evidence for spatial heterogeneity and clustering of NHL incidence was found within this region. Future epidemiological research using large-scale registries is needed to better appraise spatial variation of NHL incidence in France and to investigate possible reasons for significant clusters.

Therapy-related acute promyelocytic leukemia.

PURPOSE: To analyze patient cases of therapy-related acute promyelocytic leukemia (tAPL), occurring after chemotherapy (CT), radiotherapy (RT) or both for a prior disorder, diagnosed during the last 20 years in three European countries. PATIENTS AND METHODS: The primary disorder and its treatment, interval from primary disorder to tAPL, characteristics of tAPL, and its outcome were analyzed in 106 patients. RESULTS: Eighty of the 106 cases of tAPL were diagnosed during the last 10 years, indicating an increasing incidence of tAPL. Primary disorders were predominantly breast carcinoma (60 patients), non-Hodgkin's lymphoma (15 patients), and other solid tumors (25 patients). Thirty patients had received CT alone, 27 patients had received RT alone, and 49 patients had received both. CT included at least one alkylating agent in 68 patients and at least one topoisomerase II inhibitor in 61 patients, including anthracyclines (30 patients), mitoxantrone (28 patients), and epipodophyllotoxins (19 patients). Median interval from primary disorder to tAPL diagnosis was 25 months (range, 4 to 276 months). Characteristics of tAPL were generally similar to those of de novo APL. With treatment using anthracycline-cytarabine-based CT or all-trans-retinoic acid combined with CT, actuarial survival was 59% at 8 years. CONCLUSION: tAPL is not exceptional, and develops usually less than 3 years after a primary neoplasm (especially breast carcinoma) treated in particular with topoisomerase II-targeted drugs (anthracyclines or mitoxantrone and less often etoposide). Characteristics and outcome of tAPL seem similar to those of de novo APL.

Nonrandom fusion of L-plastin(LCP1) and LAZ3(BCL6) genes by t(3;13)(q27;q14) chromosome translocation in two cases of B-cell non-Hodgkin lymphoma.

The LAZ3(BCL6) gene on chromosome band 3q27 is nonrandomly disrupted in B-cell non-Hodgkin lymphoma (B-NHL) by chromosomal translocations clustered within a 3.3-kb MTC (major translocation cluster) located between the two first noncoding exons. These translocations generally result in the expression of a chimeric mRNA transcript between the LAZ3 gene and sequences derived from the partner chromosome. Using RACE RT-PCR, we previously demonstrated fusion of LAZ3 with the RhoH/TTF gene, a hemopoietic cell-specific small GTPase involved in cytoskeleton organization, and with the BOB1/OBF1 gene, a B-cell-specific coactivator of octamer-binding transcription factors, following translocations t(3;4)(q27;p13) and t(3;11)(q27;q23), respectively. Here we report the identification of the L-Plastin(LCP1) gene as a novel LAZ3 partner in chimeric transcripts resulting from a t(3;13)(q27;q14) translocation, in two cases of B-cell lymphoma. As a consequence of the translocation, the 5' regulatory region of each gene was exchanged, creating both LCP1-LAZ3 and reciprocal LAZ3-LCP1 fusion transcripts in one case, and only a LCP1-LAZ3 fusion transcript in the other. The 13q14 chromosome region is frequently disrupted in various proliferative disorders, and the LCP1 gene defines a new breakpoint site in this region. This gene encodes an actin-binding protein and is the second LAZ3 partner gene, with the RhoH/TTF gene, involved in actin cytoskeleton organization. Genes Chromosomes Cancer 26:97-105, 1999.

The VIM3-AraC regimen followed by autologous stem cell transplantation in refractory or relapsing aggressive non-Hodgkin's lymphoma. A prospective study of 71 consecutive cases.

We evaluated with an intent-to-treat analysis the response rate, the disease-free survival (DFS), and the overall survival after a multidrug salvage regimen (VIM3ARAC), followed by stem-cell transplantation (SCT) in case of response, in patients with aggressive non-Hodgkin's lymphoma (NHL) who progressed on or after the first-line therapy. Seventy-one patients (refractory: 15; relapse 'on therapy': 36; and relapse 'off therapy': 20) received two courses of VIM3ARAC (teniposide, ifosfamide, mitoxantrone, mitoguazone, high-dose methotrexate, high-dose cytarabine, prednisolone). SCT was performed only in patients with minimal disease after the second course. The response rate was 72%. It was not influenced by response to first-line therapy. Forty-eight patients (68%), including 32 complete responders, fulfilled response criteria for SCT. Thirty-six patients underwent SCT (allogeneic: 3; autologous: 33). The 4-year DFS rate of the 48 responding patients was 39%. The actuarial survival at 4 years was 34% for all patients. Relapse off therapy and a performance status <2 at relapse were the only two independent favorable prognostic factors for survival. In conclusion, VIM3AraC is associated with a high response rate in relapsing and refractory aggressive NHL. Up to half of the patients could receive SCT. This chemotherapy, followed by SCT could durably salvage 34% of these patients.

Translocation (3;13)(q27;q14): a nonrandom and probably secondary structural change in non-Hodgkin lymphomas.

Three cases of (3;13)(q27;q14) translocation observed in different histological types of non-Hodgkin lymphomas (NHLs) are reported here. This new recurring translocation in NHL was secondary in at least two of the patients because it was associated with another specific change [i.e., t(8;14) (q24;q32) in Burkitt lymphoma and t(14;18)(q32;q21) in typical follicular lymphoma]. In two of the cases for which molecular analysis was performed, a rearrangement of the LAZ-3/BCK-6 gene was found.

Very low incidence of p53 antibodies in adult non-Hodgkin's lymphoma and multiple myeloma.

In several types of solid tumours, circulating antibodies to p53 are seen in about a third of cases with a p53 mutation, but are absent in cases without p53 mutation. Therefore detection of those antibodies has relatively low sensitivity but high specificity in the detection of p53 mutations. We looked for circulating p53 antibodies by ELISA in 56 adult non-Hodgkin's lymphoma (NHL) and 80 multiple myeloma cases. A certain or highly probable p53 mutation was found by SSCP analysis, immunocyto- or immunohistochemistry in 8/35 (23%) NHL cases and 2/19 (10%) MM cases analysed by these techniques. None of the 80 MM cases and only one of the 56 cases of NHL had circulating p53 antibodies. The positive case had Burkitt's lymphoma and a p53 missense mutation at codon 273. Thus, very few MM and NHL patients with a p53 mutation develop p53 antibodies and this test does not appear to be useful in haematological malignancies.

[Malignant non-Hodgkins lymphoma manifested in an ovarian tumor. Five case reports]. / Lymphomes malins non hodgkiniens révélés par une tumeur ovarienne. A propos de 5 observations.

Five cases of non-Hodgkin malignant lymphoma (NHML) presenting as ovarian tumours are reported. All corresponded to disseminated lymphomatous disease, none was of low grade. Ultrasound showed a solid, most often homogeneous, hypoechoic, bilateral mass in 4 of 5 cases. Its association with many lymph nodes and mainly parenchymal localisation suggested of the NHML. Only histologic and immunohistochemical findings may provide the final diagnosis. The biopsy for those studies should be obtained as least invasively as possible because treatment of NHML is chemotherapy.

Autologous bone marrow transplantation as consolidation therapy may prolong remission in newly diagnosed high-risk follicular lymphoma: a pilot study of 34 cases.

We evaluated early intensification followed by autologous bone marrow transplantation (ABMT) using marrow purged by mafosfamide in patients with high-risk low-grade follicular lymphoma (LGFL) reaching a status of minimal disease (MD). Thirty-four patients entered the program. All fulfilled at least one of the following criteria at diagnosis: a bulky tumor > 7 cm; three or more adenopathies > 3 cm; massive pleural or peritoneal effusion; massive splenomegaly; B symptoms; platelet count < 100 x 10(9)/l. Twenty-one patients had bone marrow involvement. Twenty-six patients received ACVBP, and eight CVP as front-line therapy. Twenty-one (62%) patients achieved MD status, 18 reached intensification. At 4 years, the time to treatment failure is 55 +/- 9%, and the probability of persisting remission is 75 +/- 11%. Comparison by intention to treat of the 26 patients who received ACVBP as front-line therapy to 14 historical high-risk LGFL similarly treated in our institution without intensification, showed better results for the intensified group (P = 0.04 for both probability of persisting remission and time to treatment failure). These results indicate that early intensification using marrow purged with mafosfamide is a therapeutic option which may bring benefit to patients with high-risk LGFL.

Comparison of technetium-99m methoxyisobutylisonitrile and gallium-67 citrate scanning in the assessment of lymphomas.

The aim of this study was to compare the value of scintigraphy using technetium-99m methoxyisobutylisonitrile (MIBI) with that of scintigraphy using gallium-67 citrate in the assessment of Hodgkin's disease and non-Hodgkin's lymphoma and to relate these results with those of CT scan and MRI. Fifty-eight patients were included either for a follow-up examination or for monitoring of their treatment. Twenty-three residual masses were studied. A whole-body scan was performed, followed by single-photon emission computed tomography (SPET) 20 min after injection of 740 MBq of 99mTc-MIBI and 72 h after injection of 185 MBq of 67Ga citrate. The overall sensitivity of 99mTc-MIBI and 67Ga citrate was 71% and 68%, respectively, and the overall specificity was 76% and 44%, respectively. For residual masses, the sensitivity was 44% with both tracers and the specificity was 80% with 99mTc-MIBI and 53% with 67Ga citrate. The positive predictive values were 85% and 68% and the negative predictive values were 59% and 44%, respectively. The signal-to-background ratio was 1.5 for 99mTc-MIBI and 2 for 67Ga citrate. At present, 99mTc-MIBI cannot replace 67Ga citrate in the assessment of lymphomas.

Is there still a role for low-dose cytosine arabinoside in de novo acute myeloid leukemia in the elderly? A report on 77 cases.

Seventy-seven elderly patients (median age 72, range 59-85) with de novo AML were treated with low-dose Ara C (10 mg/m2/12 h over 21 days, for one or two courses). Thirteen (17%) achieved complete remission (CR), 16 (21%) partial remission (PR); 28 (35%) had resistant leukemia, and 20 (26%) early death or death during hypoplasia. Most (86%) of the patients had severe pancytopenia and 58% were hospitalized. Overall median survival was 3 months. Median duration of CR was 9 months. Five CR were longer than 1 year, and two were longer than 4 years. All but one PR were < or = 9 months, and 12/16 were < or = 4 months. Karnofsky index and karyotype (the latter performed for 52 patients) were the only significant prognostic factors of response to treatment (including CR+PR) and survival: poor response rate (8%) and survival (median 0.7 months) were found in patients with Karnofsky index < 60, compared with 44% and 4 months, respectively, in patients with Karnofsky index > or = 60; likewise, patients with rearrangements of chromosome 5 and/or 7 or complex rearrangements had a response rate of 13% and median survival of 1.5 months, compared with 68% and 8 months, respectively, in patients with normal karyotype or single abnormalities (not involving chromosomes 5, 7, or 8). Patients with isolated trisomy 8 had a response rate of 37% but short median survival (2.5 months). Significantly longer survival was seen in responders. Our findings suggest that, overall, low-dose Ara C yields limited results in AML in the elderly. However, it could remain a useful option in elderly patients with AML who are not candidates for intensive chemotherapy (even with the support of growth factors), provided their general condition is not too altered and they do not have an "unfavorable" karyotype (i.e., rearrangements of chromosomes 5 or 7 or complex abnormalities).

Therapy-related acute promyelocytic leukemia: a report on 16 cases.

PURPOSE: To analyze the type of prior tumor and treatment in therapy-related acute promyelocytic leukemia (tAPL) that occurs after chemotherapy and/or radiotherapy (RT), and the hematologic characteristics and outcome of tAPL. PATIENTS AND METHODS: Sixteen patients with tAPL who were gathered during a 10-year period (1982 to 1991) in seven hematologic centers were analyzed retrospectively. RESULTS: There were 13 women and three men. The median age was 46 years (range, 12 to 82). Prior tumor was breast carcinoma in 10 cases, another solid tumor in three cases, and lymphoma in three cases. Two patients had received RT alone, and 14 had received chemotherapy (with RT in 11 cases). Prior chemotherapeutic agents generally included a combination of cyclophosphamide (used for limited periods), fluorouracil (5-FU), vinca alkaloids, and doxorubicin, mitoxantrone, or etoposide (VP16). By contrast, alkylating agents other than cyclophosphamide had been used in only two patients. Median interval between onset of treatment for the prior tumor and diagnosis of APL was 25 months. No patient had a known preleukemic phase. Hematologic and cytogenetic characteristics of the cases of tAPL were identical to those of the usual de novo APL, which included the presence of t(15; 17) in nine of the 10 patients tested. Two patients had early death. Seven patients were treated with intensive chemotherapy, and six achieved complete remission (CR). Three of them subsequently relapsed. Seven patients were treated with all-trans-retinoic acid (ATRA), and four achieved CR through the differentiation of blasts into mature granulocytes. None has relapsed so far. CONCLUSIONS: Our findings suggest that tAPL is not exceptional, and usually has several features in common with other types of therapy-related AML with specific karyotype (ie, t(8;21),t(9;11), inv(16)): solid tumor rather than hematologic malignancy as primary tumor, short interval of development, absence of known preleukemic phase, prior chemotherapy with a combination of several drugs that often included an agent that targets topoisomerase II (doxorubicin or mitoxantrone, but less often VP16). Hematologic characteristics and response to therapy (intensive chemotherapy or ATRA) in tAPL do not seem to differ from those of de novo APL.

Secondary acute lymphoblastic leukemia with t (4;11): report on two cases and review of the literature.

We report two cases of secondary acute lymphoblastic leukemia (ALL) with t (4;11) (q21;q23) translocation occurring after chemotherapy and radiotherapy for a prior cancer. Seven previously published cases of secondary ALL with t (4;11) (q21;q23) are also reviewed. Most patients had received a combination of topoisomerase II inhibitors (anthracyclines, mitoxantrone, or the epipodophillotoxin derivatives VP16 or VM26) and cyclophosphamide, which have also been implicated in the pathogenesis of secondary acute myeloid leukemia (AML) with 11q23 rearrangements. These observations give further support to the existence of a subgroup of secondary acute leukemias with cytogenetic findings "specific" for de novo ALL and AML, especially those with translocations involving the 11q23 region.