FDG-PET-driven consolidation strategy in diffuse large B-cell lymphoma: final results of a randomized phase 2 study.

Dose-dense induction and up-front consolidation with autologous stem cell transplantation (ASCT) remain controversial issues when treating patients with high-risk diffuse large B-cell lymphoma. GELA designed a randomized phase 2 trial evaluating the efficacy of either rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone (R-ACVBP) or rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP14) induction and a positron emission tomography (PET)-driven ASCT or standard immunochemotherapy (SIC) consolidation in age-adjusted international prognosis index 2 (aaIPI2)-aaIPI3 patients. PET was performed at baseline, after 2 (PET2) and 4 (PET4) induction cycles, and centrally assessed using international harmonization project (IHP) criteria. PET2-/PET4- patients were assigned SIC, PET2+/PET4- patients were assigned ASCT, and PET4+ patients were treated with the investigator's choice. The primary end-point was the 2007 international working group complete response (CR) rate after induction. Change in maximum standard uptake value (ΔSUVmax) after PET assessment was explored. Two hundred eleven patients were randomly assigned to R-ACVBP (n = 109) or R-CHOP14 (n = 102). PET4-/CR rates were 53%/47% with R-ACVBP and 41%/39% with R-CHOP14 (CR 95% confidence interval [CI], 38%-67% and 28%-54%, respectively; P = .076). Consolidation in the R-ACVBP and R-CHOP14 groups was SIC in 26% and 23% of patients and ASCT in 28% and 18% of patients, respectively. PET4 positivity was higher with R-CHOP14 vs R-ACVBP (54% vs 41%; P = .08), leading to more salvage therapy (37% vs 26%; P = .07) and lower event-free survival (EFS; 4-year EFS, 31% vs 43%; P < .01), but progression-free survival (PFS) and overall survival (OS) were similar in both groups. PET2-/PET4- and PET2+/PET4- patients had similar outcomes. Using ΔSUVmax, 79% of the patients were PET2-/PET4- ΔSUVmaxPET0-4 >70% was associated with better outcome (4-year PFS, 84% vs 35%; 4-year OS, 91% vs 57%; P < .0001), whatever the consolidation. Superiority of R-ACVBP over R-CHOP14 was not established, as IHP criteria did not properly reflect disease control. ΔSUVmax may help better select patients needing an alternative to SIC, including ASCT.

Predictive factors for a single successful cytapheresis session during the first mobilisation.

To avoid repeated apheresis, the objective of this study was to analyse the predictive factors for a single successful cytapheresis during the first mobilisation. The pre-collection characteristics of 170 lymphoma and 95 myeloma patients were analysed. Among 60 lymphoma patients who had less than 30 CD34 cells/mm(3) the day before the first apheresis, an increase in the CD34 cell count between Day -1 and Day 1 was predictive of first stem cell mobilisation success, with a sensitivity of 100% if the Day 1 was higher than 30/mm(3) (10/60 patients). Success rate of obtaining an appropriate number of stem cells in one apheresis was 120 among 170 patients.

Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: the IFM experience on 1195 patients.

Deletions of the 1p region appear as a pejorative prognostic factor in multiple myeloma patients (especially 1p22 and 1p32 deletions) but there is a lack of data on the real impact of 1p abnormalities on an important and homogeneous group of patients. To address this issue we studied by fluorescence in situ hybridization (FISH) the incidence and prognostic impact of 1p22 and 1p32 deletions in 1195 patients from the IFM (Institut Francophone du Myélome) cell collection. Chromosome 1p deletions were present in 23.3% of the patients (271): 15.1% (176) for 1p22 and 7.3% (85) for 1p32 regions. In univariate analyses, 1p22 and 1p32 appeared as negative prognostic factors for progression-free survival (PFS): 1p22: 19.8 months vs 33.6 months (P<0.001) and 1p32: 14.4 months vs 33.6 months (P<0.001); and overall survival (OS): 1p22: 44.2 months vs 96.8 months (P=0.002) and 1p32: 26.7 months vs 96.8 months (P<0.001). In multivariate analyses, 1p22 and 1p32 deletions still appear as independent negative prognostic factors for PFS and OS. In conclusion, our data show that 1p22 and 1p32 deletions are major negative prognostic factors for PFS and OS for patients with MM. We thus suggest that 1p32 deletion should be tested for all patients at diagnosis.

Cryopreservation, semen use and the likelihood of fatherhood in male Hodgkin lymphoma survivors: an EORTC-GELA Lymphoma Group cohort study.

STUDY QUESTION: How does the successful cryopreservation of semen affect the odds of post-treatment fatherhood among Hodgkin lymphoma (HL) survivors? SUMMARY ANSWER: Among 334 survivors who wanted to have children, the availability of cryopreserved semen doubled the odds of post-treatment fatherhood. WHAT IS KNOWN ALREADY: Cryopreservation of semen is the easiest, safest and most accessible way to safeguard fertility in male patients facing cancer treatment. Little is known about what proportion of patients achieve successful semen cryopreservation. To our knowledge, neither the factors which influence the occurrence of semen cryopreservation nor the rates of fatherhood after semen has been cryopreserved have been analysed before. STUDY DESIGN, SIZE, DURATION: This is a cohort study with nested case-control analyses of consecutive Hodgkin survivors treated between 1974 and 2004 in multi-centre randomized controlled trials. A written questionnaire was developed and sent to 1849 male survivors. PARTICIPANTS/MATERIALS, SETTING, METHODS: Nine hundred and two survivors provided analysable answers. The median age at treatment was 31 years. The median follow-up after cryopreservation was 13 years (range 5-36). MAIN RESULTS AND THE ROLE OF CHANCE: Three hundred and sixty-three out of 902 men (40%) cryopreserved semen before the start of potentially gonadotoxic treatment. The likelihood of semen cryopreservation was influenced by age, treatment period, disease stage, treatment modality and education level. Seventy eight of 363 men (21%) used their cryopreserved semen. Men treated between 1994 and 2004 had significantly lower odds of cryopreserved semen use compared with those treated earlier, whereas alkylating or second-line (chemo)therapy significantly increased the odds of use; no other influencing factors were identified. We found an adjusted odds ratio of 2.03 (95% confidence interval 1.11-3.73, P = 0.02) for post-treatment fatherhood if semen cryopreservation was performed. Forty-eight out of 258 men (19%) who had children after HL treatment became a father using cryopreserved semen. LIMITATIONS, REASONS FOR CAUTION: Data came from questionnaires and so this study potentially suffers from response bias. We could not perform an analysis with correction for duration of follow-up or provide an actuarial use rate due to lack of dates of semen utilization. We do not have detailed information on either the techniques used in cryopreserved semen utilization or the number of cycles needed. STUDY FUNDING/COMPETING INTERESTS: Lance Armstrong Foundation, Dutch Cancer Foundation, René Vogels Stichting, no competing interests.

Lymphoma occurring in patients over 90 years of age: characteristics, outcomes, and prognostic factors. A retrospective analysis of 234 cases from the LYSA.

BACKGROUND: Lymphoma occurring in patients aged 90 or older is not uncommon, and its incidence is expected to increase over time. Management of these patients is difficult given their underlying fragility and the lack of information regarding this population. PATIENTS AND METHODS: We retrospectively analyzed 234 patients diagnosed with lymphoma at the age of 90 years or older (90+) between 1990 and 2012 to describe their characteristics, management, outcomes and prognostic factors. RESULTS: The median age was 92 years; 88% were B-cell lymphomas consisting mainly in diffuse large B-cell lymphoma. The median overall survival (OS) was 7.2 months (range, 0-92 months) for the 227 patients with non-Hodgkin Lymphoma (NHL), with a significant difference between aggressive and indolent NHL (5.2 months versus 19.4 months, respectively). We further analyzed 166 NHL patients for whom detailed characteristics were available. Among these patients, 63.5% received a treatment, either local (7.5%) or systemic (56%). Lymphoma was reported as the main cause of death (40%). Treatment administration was associated with improved OS in patients with aggressive (P < 0.001) but not indolent NHL (P = 0.96). In patients with aggressive NHL, hypoalbuminemia appeared as a strong and independent negative prognostic factor. CONCLUSIONS: The median OS is short in 90+ patients diagnosed with lymphoma but some patients experience prolonged survival. Lymphoma represents the main cause of death in these patients. Treatment may improve survival of selected patients with aggressive but not indolent NHL. Management of these patients may be guided by prognostic factors identified in this study, notably serum albumin.

Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B).

BACKGROUND: The superiority of a chemotherapy with doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP) in comparison with cyclophosphamide, doxorubicin, vincristin and prednisone plus radiotherapy for young patients with localized diffuse large B-cell lymphoma (DLBCL) was previously demonstrated. We report the results of a trial which evaluates the role of rituximab combined with ACVBP (R-ACVBP) in these patients. PATIENTS AND METHODS: Untreated patients younger than 66 years with stage I or II DLBCL and no adverse prognostic factors of the age-adjusted International Prognostic Index were randomly assigned to receive three cycles of ACVBP plus sequential consolidation with or without the addition of four infusions of rituximab. RESULTS: A total of 223 patients were randomly allocated to the study, 110 in the R-ACVBP group and 113 in the ACVBP group. After a median follow-up of 43 months, our 3-year estimate of event-free survival was 93% in the R-ACVBP group and 82% in the ACVBP group (P = 0.0487). Three-year estimate of progression-free survival was increased in the R-ACVBP group (95% versus 83%, P = 0.0205). Overall survival did not differ between the two groups with a 3-year estimates of 98% and 97%, respectively (P = 0.686). CONCLUSION: In young patients with low-risk localized DLBCL, rituximab combined with three cycles of ACVBP plus consolidation is significantly superior to ACVBP plus consolidation alone.

Long-term follow-up of high-dose treatment with autologous haematopoietic progenitor cell support in 693 patients with follicular lymphoma: an EBMT registry study.

To evaluate the outcome of a large series of patients who received high-dose treatment (HDT) for follicular lymphoma (FL), 693 patients undergoing HDT (total-body irradiation (TBI)-containing regimen: 58%; autologous bone marrow (BM)/peripheral blood progenitor cells (PBPCs): 378/285 patients) were included in the study. A total of 375 patients (54%) developed recurrent lymphoma, 10-year progression-free survival (PFS) being 31%. On multivariate analysis, younger age (P=0.003) and HDT in first complete remission (CR1) (P<0.001) correlated with longer PFS. With a median follow-up of 10.3 years, 330 patients died. Ten-year overall survival (OS) from HDT was 52%. Shorter OS was associated on multivariate analysis with older age (P<0.001), chemoresistant disease (P<0.001), BM+PBPC as source of stem cells (P=0.007) and TBI-containing regimens (P=0.004). Thirty-nine patients developed secondary myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML), in 34 cases having received TBI as the conditioning regimen. The 5-year non-relapse mortality (NRM) was 9%. On multivariate analysis, older age (P<0.001), refractory disease (P<0.001) and TBI (P=0.04) were associated with a higher NRM. This long follow-up study shows a plateau in the PFS curve, suggesting that a selected group of patients might be cured with HDT. On the downside, TBI-containing regimens are associated with a negative impact on survival.

Comparison of a quantitative PCR method with FISH for the assessment of the four aneuploidies commonly evaluated in CLL patients.

Four chromosomal defects associated with outcome are commonly evaluated by fluorescent in situ hybridization (FISH) in chronic lymphocytic leukemia (CLL), namely deletions of the 13q13-q14, 11q22 and 17p13 regions and trisomy 12. In this study, we compared a quantitative PCR method--quantitative multiplex PCR of short fluorescent fragment (QMPSF)--with FISH for the detection of these acquired aneuploidies in a series of 110 patients with Binet stage A CLL. Genes located in the deleted or gained regions were selected as target genes and amplified using a method based on the simultaneous amplification of short fluorescent genomic fragments under quantitative conditions. A chromosomal imbalance involving one or several of the four loci was detected by either method in 72 patients (65%). A chromosome 13 deletion was present in 61 patients (54%), a 11q22 deletion in nine (8%), a trisomy 12 in nine and a 17p deletion in one. FISH and QMPSF results were identical for 103 out of 110 patients and discrepancies could be explained in most cases. This study demonstrates that a quantitative multiplex PCR represents a cost-effective method that could replace FISH in CLL patients. However, although QMPSF is perfectly adapted to the detection of primary defects, care should be taken when searching for clonal evolutions present in a small proportion of tumor cells.

Hypodiploidy is a major prognostic factor in multiple myeloma.

Conventional karyotypes performed before any treatment in 208 patients with multiple myeloma were reviewed by the Groupe Français de Cytogénétique Hématologique. A total of 138 patients displayed complex chromosomal abnormalities (CCAs). According to the chromosome number pattern, a first group of 75 patients had a hyperdiploid karyotype. A second group of 63 patients referred to as the hypodiploid group had either pseudodiploid, hypodiploid, or near-tetraploid karyotypes. Of 159 treated patients available for survival analysis, 116 had an abnormal karyotype. The comparison of overall survival (OS) between hyperdiploid and hypodiploid patients showed a highly significant difference (median OS 33.8 vs 12.6 months, respectively, P <.001). The presence of 14q32 rearrangements (36 of 116 patients) worsened the prognosis (median OS 17.6 vs 29.9 months, P <.02). The presence of chromosome 13q abnormalities (13qA, 63 patients) did not modify OS in CCA patients (median OS 20.6 vs 27.8 months, P <.59). However, taking into account the whole series including normal karyotypes, 13qA (63 of 159 patients) had a significant impact on OS (median 20.6 vs 37.1 months, P <.04). In the same way, the presence of a hypodiploid karyotype (52 of 159 patients) had a strong prognostic value (OS 12.8 vs 44.5 months, P <.000 01). A multivariate analysis including stage, beta2-microglobulin, bone marrow plasmocytosis, treatment type, 13qA, and hyperdiploidy and hypodiploidy showed that a hypodiploid karyotype was the first independent factor for OS (P <.001), followed by treatment approach. These results confirm that the chromosome number pattern of malignant plasma cells is a very powerful prognostic factor in newly diagnosed multiple myeloma patients.

[Intramedullary spinal cord metastasis and leptomeningeal involvement in Hodgkin's disease. Case report and review of the literature]. / Atteinte de la moelle épinière et envahissement méningé lors d'une maladie de Hodgkin. A propos d'un cas et revue de la littérature.

INTRODUCTION: Central nervous system, especially spinal cord involvement, is unusual in Hodgkin's disease. We report the case of a patient with refractory Hodgkin's disease who presented with intramedullary involvement. EXEGESIS: A 36-year-old woman presented with weakness of the right lower extremity and sphincter dysfunction 13 years after initial diagnosis of Hodgkin's disease. Magnetic resonance imaging showed intraspinal tumor with contrast enhancement extending from C7 to D1. Cerebrospinal fluid examination revealed the presence of Reed-Sternberg cells. Specific intramedullary spinal cord metastasis and leptomeningeal involvement were confirmed. Despite intrathecal chemotherapy the neurologic deficit progressed to paraplegia and the patient died 2 months later. CONCLUSION: Intramedullary spinal cord metastases rarely occur in the course of Hodgkin's disease. Except for the initial presentation, their prognosis is poor despite early diagnosis with magnetic resonance imaging. Other causes such as epidural cord compression, paraneoplasic myelopathy, granulomatous angiitis and radiation myelopathy are still delated.

Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different diseases.

We report the cytogenetic results obtained in 81 multiple myeloma (MM) patients with abnormal karyotypes. Most karyotypes were complex with numerical and structural abnormalities but the analysis of chromosomal abnormalities allowed identification of two cytogenetic patterns depending on the chromosome number: a first hyperdiploid pattern (54%) with recurrent trisomies 3, 5, 7, 9, 11, 15 and 19 and a second pattern (46%) showing either pseudodiploid, hypodiploid or near-tetraploid karyotypes. Structural abnormalities were present in all but five hyperdiploid karyotypes, and frequently involved lymphoid breakpoints: immunoglobulin gene regions (36 cases) or chromosome 11q13 region (21 cases). Numerous other structural aberrations were detected; the most frequent involved chromosome 1 and chromosome 13. Structural abnormalities were significantly more frequent in the second hypodiploid group. When analyzing the results obtained in the 60 patients studied at the time of diagnosis, a prognostic correlation was found between the cytogenetic pattern and overall survival: hyperdiploid patients had a longer survival than patients belonging to the pseudo/hypo/near-tetraploid group (median survival 36.8 vs 18.2 months, P < 0.04). These results suggest that MM could correspond to two closely related diseases.

Early intensive therapy with autologous stem cell transplantation in advanced Hodgkin's disease: retrospective analysis of 158 cases from the French registry.

This retrospective study was undertaken to evaluate cure rates, toxicity and late effects of early intensive therapy followed by autologous stem cell transplantation (ASCT) in patients with advanced Hodgkin's disease (HD). One hundred and fifty-eight cases of ASCT registered in the French database (SFGM) were retrospectively analyzed. Disease status at the time of ASCT was first partial response (PR) in 85, first complete remission (CR1) in 45 or primary refractory in 28 cases. The median time interval between diagnosis and ASCT was 7 months (range 4-13). At the time of analysis in December 1995, 121/158 patients (76.6%) were alive, including 111 (70.2%) in continuous CR with a median follow-up for surviving patients of 46 months (range 8-123). Peri-ASCT toxic death rate was 3%, and the actuarial risk of new malignancies was 4.9% at 5 years. The cumulative probability of 5-year overall survival (OS) was 75.2% for the entire group of patients, 80.6% for the chemosensitive ones, and 33.9% for the primary refractory (chemosensitive vs refractory, P < 0.0001). The cumulative probability of 5-year event-free survival (EFS) was 66.1% for the entire group of patients, 73.7% for the chemosensitive ones, and 26.1% for the primary refractory (chemosensitive vs refractory, P < 0.0001). The only significant prognostic factor for both OS and EFS was disease status at the time of ASCT. Early ASCT in advanced HD is feasible, with a low risk of toxicity and without a higher rate of late effects compared with conventional treatment. Results achieved in chemosensitive patients at the time of transplantation lay the basis of future prospective randomized trials comparing ACST as front-line treatment to conventional treatment in high-risk cases.

Lactobacillus species as emerging pathogens in neutropenic patients.

The intensive use of broad-spectrum antibiotics in the context of prolonged and severe neutropenia has contributed to the emergence of unusual pathogens. Four new cases of severe Lactobacillus infections-three of septicemia and one of pneumonia-are reported. They occurred in patients with acute leukemia who had chemotherapy-induced neutropenia. All patients were treated in the same intensive care unit and received the same antimicrobial prophylaxis which included a total bowel decontamination containing vancomycin. The four patients were treated with a combination of intravenous ceftazidime and vancomycin prior to the development of Lactobacillus infection. Improvement in the condition of all patients was obtained with a treatment including penicillin and concurrent recovery of granulopoiesis.

Peripheral blood stem cell transplantation for relapsed or refractory aggressive lymphoma in patients over 60 years of age.

Intensive chemotherapy with autologous bone marrow transplantation is now considered the treatment of choice for young patients with sensitive relapse of non-Hodgkin's lymphoma (NHL) but results of this procedure in older patients remain unknown. We evaluated the feasibility of two cycles of salvage therapy followed by an autologous peripheral blood stem cell (PBSC) transplantation in 13 patients aged more than 60 years (median age: 62; range 61-72) suffering from relapsed (n = 10) or refractory (n = 3) aggressive NHL. All patients had previously received first-line treatment containing doxorubicin. An association of ifosfamide, VP16, cytosine-arabinoside with or without high-dose methotrexate was used as salvage and priming therapy prior to collection of PBSC. All patients received G-CSF following salvage therapy. PBSC collection could be performed in 10 patients and yielded a median number of CFU-GM: 98.4 x 10(4)/kg (range 68-369). Nine patients underwent a transplantation using BEAM conditioning regimen. The median time to granulocyte and platelet recovery was 13 days (range respectively: 9-25 and 9-16). One patient died from sepsis after transplantation. The main adverse experience occurring after transplantation was a prolonged decline of performance status. Seven patients achieved a complete remission and one failed to respond. Three patients are still alive in CR. We conclude that PBSC collection was possible in selected patients over 60 years of age with refractory or relapsed aggressive NHL and myeloablative therapy could be used with tolerable toxicity. Hematologic recovery and organ toxicity appears to be similar to those observed in younger patients. Deterioration of performance status after transplantation is the most important factor that could limit this procedure. Further investigations are necessary to determine which patients will be able to benefit by this procedure in terms of survival and quality of life.

Durable remission of a relapsing primary central nervous system lymphoma after autologous bone marrow transplantation.

A 30-year-old patient with a relapsing primary central nervous system lymphoma (PCNSL), was successfully treated with salvage chemotherapy and high-dose therapy including drugs that cross the blood-brain barrier followed by ABMT. Cerebrospinal irradiation was administered after hematological recovery. Six years after transplantation the patient is alive without evidence of recurrent disease with a good neuropsychological status. This result could justify further studies of aggressive management of PCNSL in relapse.

Correlation between CD34 expression and chromosomal abnormalities but not clinical outcome in acute myeloid leukemia.

The hemopoietic stem cell marker CD34 has been reported to be a useful predictor of treatment outcome in acute myeloid leukemia (AML). Previous data suggested that CD34 expression may be associated with other poor prognosis factors in AML such as undifferentiated leukemia, secondary AML (SAML), and clonal abnormalities involving chromosome 5 and 7. In order to analyze the correlations between the clinicopathologic features, cytogenetic and CD34 expression in AML, we retrospectively investigated 99 patients with newly diagnosed AML: 85 with de novo disease and 14 with secondary AML (SAML). Eighty-six patients who received the same induction chemotherapy were available for clinical outcome. Defining a case as positive when > or = 20% of bone marrow cells collected at diagnosis expressed the CD34 antigen, forty-five patients were included in the CD34 positive group. Ninety patients had adequate cytogenetic analysis. Thirty-two patients (72%) with CD34 positive AML exhibited an abnormal karyotype whereas 15 patients (28%) with CD34 negative AML had abnormal metaphases (P < 0.01). Monosomy 7/7q- or monosomy 5/5q- occurred in 10 patients and 8 of them expressed the CD34 antigen (P < 0.05). All patients with t(8;21) which is considered as a favorable factor in AML had levels of CD34 >/= 20% (P < 0.05). We did not find any association between CD34 expression and attainment of complete remission, overall survival, or disease-free survival. In conclusion, the variations of CD34 expression in AML are correlated with cytogenetic abnormalities associated both with poor and favorable outcome. The evaluation of the correlations between CD34 antigen and clinical outcome in AML should take into account the results of pretreatment karyotype.

Ifosfamide, etoposide, cytarabine, and methotrexate as salvage chemotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma.

BACKGROUND: Patients with relapsed or resistant non-Hodgkin's lymphoma (NHL) have a poor prognosis and are rarely cured with usual salvage chemotherapy. Intensive treatment with the support of peripheral blood stem cells (PBSC) may be an effective therapy for these patients. We used a combination of ifosfamide, etoposide, cytarabine, and methotrexate (IVAM) with the intention both to reduce tumor burden and collect PBSC prior to transplantation. METHODS: Thirty-one patients (17 with relapsed NHL and 14 with refractory NHL) were treated with 2 courses of chemotherapy: IVAM regimen (ifosfamide, 1500 mg/m2 daily for 5 days plus mesna; etoposide, 150 mg/m2 daily for 3 days; cytarabine, 100 mg/m2 daily for 3 days; and methotrexate, 3 g/m2 on Day 5, with leucovorin rescue). Twenty-three patients had an intermediate grade and 8 patients had a high grade lymphoma. RESULTS: After IVAM therapy, 19 patients (61%) achieved complete response, 8 patients (26%) achieved partial response and 4 patients (13%) failed to respond. The major toxicity of IVAM was myelosuppression, but there were no toxic deaths. PBSC harvest could be performed in 29 patients (94%) with a median granulocyte-macrophage colony-forming unit count of 55 x 10(4)/kg (range, 2-391 x 10(4)/kg). Three patients could not undergo transplantation because of disease progression. One patient received a syngeneic transplant, 25 patients received PBSC transplantation, and 2 patients received a bone marrow transplant. In an intent-to-treat analysis, the overall survival rate at 4 years was 37% for the whole group (95% confidence interval: 22-55). CONCLUSIONS: We conclude that IVAM is an effective salvage chemotherapy for refractory or relapsed NHL and permits PBSC collection in most of these patients.

Residual disease in B-cell chronic lymphocytic leukemia patients and prognostic value.

Twenty-two B-cell chronic lymphocytic leukemia (CLL) patients were investigated to evaluate residual disease in clinico-hematological remission. Residual disease was determined by monotypy of surface light-chain expression and by dual-color staining with CD5 and CD19 markers. Samples were analyzed on flow cytometer. Total CD19+ cells above 25%, the CD5+CD19+/total CD19+ cells ratio above 0.25, clonal excess above 0.4 were considered positive for residual disease. According to these immunological criteria, only four cases achieved phenotypic remission. Our data confirm that dual marker analysis is more sensitive than clonal excess and may predict an early relapse. Ig gene rearrangements were studied by Southern blot analysis using IGHJ and IGKC probes in fifteen cases. All 12 cases that retained a detectable rearrangement displayed a phenotypic residual disease. Conversely, in two cases, DNA analysis failed to detect the residual disease characterized by flow cytometry. In conclusion, this study suggests that in B-CLL, dual marker analysis is sensitive in predicting an early relapse in sequential evaluations of residual disease, whereas rearranged bands are undetectable when the proportion of malignant cells is low.

LAZ3 rearrangements in non-Hodgkin's lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 217 patients.

We have recently shown that an evolutionary conserved gene LAZ3, encoding a zinc finger protein, is disrupted and overexpressed in some B-cell lymphomas (mainly with a large cell component) that show chromosomal rearrangements involving 3q27. Because the breakpoints involved in these rearrangements are focused in a narrow major translocation cluster (MTC) on chromosome 3, we used genomic probes from this region to study the molecular rearrangements of LAZ3 in a large series of patients (217) with non-Hodgkin's lymphoma (NHL). Southern blot analysis showed LAZ3 rearrangement in 43 patients (19.8%). Rearrangement was found in 11 of the 84 patients (13%) with follicular lymphoma but was most frequent in aggressive lymphoma (diffuse mixed, diffuse large cell, and large cell immunoblastic subtypes), in which 31 of the 114 patients (27%) were affected. The highest proportion of LAZ3 alteration was observed in B-cell aggressive lymphoma (26 of 71 cases, 37%). Eleven of the 32 patients with 3q27 chromosomal abnormality had no LAZ3 rearrangement, suggesting the possibility of LAZ3 involvement outside the MTC. On the other hand, 18 of the 39 patients with LAZ3 rearrangement and available cytogenetic results did not have visible chromosomal break at 3q27, suggesting that almost a half of the rearrangements are not detectable by cytogenetic methods. No statistical association could be found between LAZ3 status and initial features of the disease or clinical outcome in either follicular or aggressive lymphomas. We conclude that LAZ3 alteration is a relatively frequent event in B-cell lymphoma, especially in those of aggressive histology. It could be used as a genomic marker of the disease, and further studies are needed to clarify clinical implications of these alterations.