Risk-assessment in diffuse large cell lymphoma at first relapse. A study by the Italian Intergroup for Lymphomas

BACKGROUND AND OBJECTIVES: Our aim was to identify risk factors in adults with diffuse large cell lymphoma at first relapse. DESIGN AND METHODS: We studied 474 patients observed at 45 centers in Italy. Median time from diagnosis to relapse was 395 days, median age at relapse was 55 years and median follow-up from relapse was 3.3 years. Salvage therapy consisted of polychemotherapy in 79% of patients, monochemotherapy and/or radiotherapy and/or surgery alone in 16%, and palliative therapy in 5%. Salvage treatment was intensified with high-dose chemotherapy + stem cell transplant in 20% of patients. OS and PFS were compared by sex, International Prognostic Index at diagnosis, histology, B/T phenotype, initial treatment, salvage therapy, and features at relapse: time from diagnosis, LDH, stage, performance status and bone marrow involvement. Cox models, adjusted for salvage therapy, were performed with factors related to overall survival (OS) and progression-free survival (PFS). RESULTS: Overall response (complete + partial) was 63%, OS at 3 years 35% and PFS at 3 years 26%. Relapse within 12 months from diagnosis, elevated serum lactic dehydrogenase (LDH), advanced stage and poor performance status were independent adverse factors for OS and PFS. The cumulative number of adverse factors is proposed as prognostic index for DLCL at first relapse since it identifies risk groups (p<0.0001) and has been validated (p=0.01). Moreover, it predicts OS and PFS in the selected group of patients with a responsive relapse (p<0.0001). INTERPRETATION AND CONCLUSION: Delay from initial diagnosis, LDH, stage and performance status at relapse should be balanced in comparative studies of salvage therapy of adults with DLCL. Patients with more than 2 adverse factors are one third of all cases and deserve more effective salvage treatments.     

Risk factors for poor treatment outcome and central nervous system relapse in diffuse large B-cell lymphoma with bone marrow involvement

Although several studies have described the prognostic implication of bone marrow (BM) involvement (BMI) in lymphoma, studies focused on BM-involved diffuse large B-cell lymphoma (DLBCL) are very rare and small-sized. This study was performed to examine the prognostic impact of morphologic findings of BMI by lymphoma and risk factors for central nervous system (CNS) relapse in BM-involved DLBCL. Between 1993 and 2005, 675 patients were diagnosed with DLBCL, and 88 patients who had BMI at initial diagnosis were eligible for this study. The median overall survival (OS) and failure-free survival (FFS) of 88 patients were 36.6 and 20.1 months, respectively. When three variables from BM morphologic findings (the pattern of BM infiltration, extent of BMI by lymphoma, and percentage of large cells in the infiltrate) were simultaneously included into multivariate model, the increased extent of BMI by lymphoma (≥10%) in BM area was the only negative prognostic factor, independent of the International Prognostic Index (IPI). Patients with both lower IPI scores and less extent of BMI showed an excellent prognosis with chemotherapy alone (5-year OS and FFS rates, 80% and 69%). However, morphologic BM features were not independent predictive factors for CNS recurrences. An increased lactate dehydrogenase (LDH) level at initial diagnosis was the only independent predictive factor for CNS relapse. Further efforts should be directed toward finding optimal treatment modalities based on the IPI and the extent of BMI by lymphoma. CNS prophylaxis may be considered only in patients with initial elevated LDH levels. K.-W. Lee and J. Yi equally contributed to this study.     

Bone marrow and blood involvement by non-Hodgkin's lymphoma: a study of clinicopathologic correlations and prognostic significance in relationship to the Working Formulation

In a series of 172 patients with non-Hodgkin's lymphoma (NHL) classified according to the Working Formulation (WF) the overall incidence of bone marrow infiltration (BM+) at diagnosis was 39%: 59% for low-grade (LGML), 30% for intermediate-grade (IGML), and 25% for high-grade malignant lymphomas (HGML). The features most significantly correlated with the presence of BM+ were a low grade of histological malignancy, the degree of splenomegaly and high values of LDH, while those correlated with the extent of BM+ were a non-focal pattern of BM disease, the presence of blood involvement at diagnosis, and the degree of BM fibrosis. Blood involvement was detected at diagnosis in 13% of patients, and a further 16% developed a leukemic phase during the course of the disease. Blood involvement correlated significantly with splenomegaly, bulky disease, advanced clinical stage, and extent of BM+. The presence of BM infiltration 'per se' at diagnosis did not significantly affect prognosis. However, the extent of BM disease was correlated with a poorer outcome in IGML and HGML patients. Regarding peripheral blood involvement, in LGML patients only late leukemic conversions were significantly associated with a worse prognosis. In patients with IGML and HGML, either initial or subsequent blood involvement was correlated with significantly poorer outcome.     

Bone marrow plasma cell infiltration in light chain amyloidosis: impact on organ involvement and outcome

Abstract

Objectives: Prognosis of immunoglobulin light-chain (AL) amyloidosis depends mainly on the presence of cardiac involvement and the disease burden. A higher bone marrow plasma cell (BMPC) burden has been recognized as an adverse prognostic factor. The aim of our study was to analyze the correlation between the BMPC infiltration, clinical features and outcomes in patients with AL amyloidosis.

Methods: The clinical records of 79 patients with AL amyloidosis treated at a single institution.

Results: Median BMPC infiltration at diagnosis was 11% and significantly correlated with the serum free light-chain difference (p?<?.001). Patients with more than 10% BMPCs had more frequent cardiac involvement (86 vs. 63%; p?=?.015), a trend towards a higher early mortality (27 vs. 11%; p?=?.08) and a significantly shorter progression-free survival (PFS) (median of 18 vs. 48?months, p?=?.02) and overall survival (median of 33?months vs. not reached; p?=?.046). In the multivariate analysis, a BMPC infiltration over 10% retained its adverse prognostic value for PFS (HR?=?2.26; 95% CI, 1.048–4.866; p?=?.038). The use of new drugs seemed to overcome the negative prognostic impact of a higher BMPC infiltration.

Conclusion: Higher BMPC infiltration in AL amyloidosis might be associated with increased systemic organ damage, particularly cardiac involvement and is rarely related to the development of myeloma features.     

High Ki67 index and bulky disease remain significant adverse prognostic factors in patients with diffuse large B cell lymphoma before and after the introduction of rituximab

The aim of this study was to evaluate the impact of clinical variables and biologic features on response rate (RR), overall survival (OS) and progression-free survival (PFS) in 111 patients with de novo diffuse large B cell lymphoma (DLBCL). Fifty-three patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and 58 patients were treated with R-CHOP (rituximab + CHOP). The variables predictive of RR in the CHOP group were B symptoms, age, clinical stage, bone marrow involvement, bulky disease, International Prognostic Index (IPI) and Bcl-2; in the R-CHOP group, these variables were bulky disease, bone marrow involvement, IPI and Ki67 expression >80%. Multivariate analysis showed that in patients treated with CHOP, the independent prognostic factors associated with PFS were age, bulky disease, IPI and Bcl-2 and those associated with OS were performance status, clinical stage, IPI and bone marrow involvement. In contrast, in patients treated with R-CHOP, the variable shown by multivariate analysis to be an independent prognostic factor associated with PFS was bulky disease, whereas Ki67 expression >80% was associated with OS and PFS. Our data show that a high Ki67 expression and bulky disease could represent possible predictive factors of poor prognosis, which would help to identify a high-risk subgroup of newly diagnosed DLBCL.     

Outcome prediction by extranodal involvement,IPI, R‐IPI,and NCCN‐IPI in the PET/CT and rituximab era: A Danish–Canadian study of 443 patients with diffuse‐large B‐cell lymphoma

18F‐fluorodeoxyglucose PET/CT (PET/CT) is the current state‐of‐the‐art in the staging of diffuse large B‐cell lymphoma (DLBCL) and has a high sensitivity for extranodal involvement. Therefore, reassessment of extranodal involvement and the current prognostic indices in the PET/CT era is warranted. We screened patients with newly diagnosed DLBCL seen at the academic centers of Aalborg, Copenhagen, and British Columbia for eligibility. Patients that had been staged with PET/CT and treated with R‐CHOP(‐like) 1^st line treatment were retrospectively included. In total 443 patients met the inclusion criteria. With a median follow‐up of 2.4 years, the 3‐year overall (OS) and progression‐free survival (PFS) were 73% and 69%, respectively. The Ann Arbor classification had no prognostic impact in itself with the exception of stage IV disease (HR 2.14 for PFS, P<0.01). Extranodal involvement was associated with a worse outcome in general, and in particular for patients with involvement of >2 extranodal sites, including HR 7.81 (P < 0.001) for PFS for >3 sites. Bone/bone marrow involvement was the most commonly involved extranodal site identified by PET/CT (29%) and was associated with an inferior PFS and OS. The IPI, R‐IPI, and NCCN‐IPI were predictive of PFS and OS, and the two latter could identify a very good prognostic subgroup with 3‐year PFS and OS of 100%. PET/CT‐ascertained extranodal involvement in DLBCL is common and involvement of >2 extranodal sites is associated with a dismal outcome. The IPI, R‐IPI, and NCCN‐IPI predict outcome with high accuracy. Am. J. Hematol. 90:1041–1046, 2015. © 2015 Wiley Periodicals, Inc.     

Limited usefulness of CA125 measurement in the management of Hodgkin's and non-Hodgkin's lymphoma

BACKGROUND: Several papers have reported an association of high CA125 serum levels with advanced non-Hodgkin's lymphoma (NHL) as well as a relationship between high CA125 values and poor outcome. PATIENTS AND METHODS: Ninety-nine patients with NHL or Hodgkin's disease (HD) underwent serum CA125 assessment at diagnosis. Gender, age, presence of B symptoms, performance status (PS), histology, sites of tumor involvement, presence of effusion, clinical stage, age-adjusted International Prognostic Index, C-reactive protein (CRP), Hb, lactate deshydrogenase (LDH) and beta2-microglobulin were evaluated for their association with serum CA125 levels. The impact of CA125 levels and other features on overall (OS) and progression-free (PFS) survival was also assessed. RESULTS: CA125 serum levels were elevated in 34% of the patients, including 19% of patients with aggressive NHL, 45% of patients with indolent NHL, and 29% of patients with HD. Univariate analyses showed that CA125 levels correlated with poor PS, the presence of B symptoms, advanced clinical stage, abdominal, bone marrow or mediastinal involvement, presence of effusions, high aaIPI, low Hb levels and high CRP, LDH or beta2-microglobulin levels. In multivariate analysis, bone marrow involvement, the presence of effusions, and high aaIPI were all associated with high CA125 serum levels. In univariate analyses, OS and PFS were affected by age (PFS only), poor PS, B symptoms, advanced clinical stage, bone marrow or abdominal involvement (PFS only), high aaIPI, low Hb, high CRP or beta2-microglobulin levels. OS and PFS were not different in patients with normal or elevated CA125 levels. Multivariate analyses showed significantly inferior OS and PFS in patients with high beta2-microglobulin but no influence of CA125. CONCLUSION: While CA125 serum level correlates significantly with a number of features associated with more aggressive disease, it does not enhance the performance of standard prognostic markers in the management of patients with NHL or HD.     

Clinicopathological study on peripheral T-cell non-Hodgkin lymphoma with bone marrow involvement: a retrospective analysis from China

We reviewed 173 patients with an initial diagnosis of peripheral T-cell non-Hodgkin lymphoma (PTCL) and compared the patients with bone marrow involvement (BMI) to those without to have a better understanding of the clinical characteristics, treatments, survival and prognosis of PTCLs with BMI. We found that 40% (70/173) of the patients had BMI, and its frequency was 64% in angioimmunoblastic T-cell lymphoma (TCL), 46% in PTCL unspecified, 29% in anaplastic large T-cell lymphoma, 23% in extranodal NK/T-cell lymphoma and 13% in enteropathy-type TCL. In the BMI group, 36% of patients had lymphoma-associated hemophagocytic syndrome (LAHS), compared with 8% of the patients without BMI (8/103, P < 0.001). The estimated 1-year overall survival (OS) rates of patients with LAHS in the BMI and non-BMI groups were 5 and 49%, respectively. The increased levels of lactate dehydrogenase, fasting triglycerides and β₂-microglobulin between the BMI and non-BMI groups were not significantly different, but ferritin increased significantly and liver dysfunction-related diseases were seen more in the BMI group. As much as 51% of patients of the BMI group had anemia, compared with 27% of the patients without BMI (P = 0.001). The estimated 2-year OS rates in the two groups were 10 and 34%. The estimated 2-year OS rate of the 67 patients with BMI, who did not lose to follow-up, was 22%, compared with 38% in the non-BMI group. The median survival times of the 2 groups were 120 and 356 days. The estimated 2-year OS rate of patients treated by CHOP regimen was 9%, compared with 51% of those with intensive chemotherapy, with a significant difference (log rank P = 0.0008). The median survival time of the 14 patients subjected to chemotherapy combined with l-asparaginase was 365 days and that of the 7 patients undergoing hemopoietic stem cell transplantation (HSCT) was 575 days. A total of 3 patients in a critical condition underwent plasmapheresis as initial therapy and achieved stable condition. We conclude that patients with PTCLs with BMI on initial diagnosis usually have hemaphagocytic syndrome and poor prognosis. BMI without lymphadenopathy is a patent clinical feature in most PTCLs. Patients with anemia on initial diagnosis in the BMI group usually have poor prognosis than those without. Intense chemotherapy, addition of l-asparaginase in chemotherapy and HSCT are comparatively efficient treatments of PTCLs. For patients in critical conditions, plasmapheresis before chemotherapy would lower the risk and improve the tolerance to chemotherapy.     

The role of bone marrow biopsy and FDG‐PET/CT in identifying bone marrow infiltration in the initial diagnosis of high grade non‐Hodgkin B‐cell lymphoma and Hodgkin lymphoma. accuracy in a multicenter series of 372 patients

Bone marrow infiltration (BMI), categorized as an extra‐nodal site, affects stage and is associated with poor prognosis in newly diagnosed lymphoma patients. We have evaluated the accuracy of PET/CT and bone marrow biopsy (BMB) to assess BMI in 372 lymphoma patients [140 Hodgkin Lymphoma (HL) and 232 High Grade B‐cell non‐Hodgkin Lymphoma (HG B‐NHL), among them 155 Diffuse Large B‐Cell Lymphoma (DLCL)]. For HL cases, and taking into account PET/CT, sensitivity, negative predictive value (NPV) and accuracy were 96.7, 99.3, and 99.3% while those of BMB were 32.3, 83.8, and 85%, respectively. For HG B‐NHL and considering PET/CT, sensitivity, NPV, and accuracy were 52.7, 81.7, and 84.1%, while those of BMB were 77.6, 90.2, and 90.7%, respectively. In the HG B‐NHL group, 25 patients would have been under‐staged without BMB. These results lead us to recommend PET/CT and the avoidance of BMB to assess BMI in HL. In the case of HG B‐NHL, bone marrow status should be assessed firstly by means of PET/CT; only in either focal or diffuse PET/CT with low borderline SUV max values or in negative cases, should BMB be carried out afterwards. In the HG B‐NHL setting and at the present moment, both techniques are complementary. Am. J. Hematol. 90:686–690, 2015. © 2015 Wiley Periodicals, Inc.     

Role of FDG-PET/CT in detecting lymphomatous bone marrow involvement in patients with newly diagnosed diffuse large B-cell lymphoma

To evaluate the role of FDG-PET/CT in detecting bone marrow (BM) involvement, pre-treatment bilateral bone marrow biopsies (BMBs) and FDG-PET/CT scans of 89 patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-CHOP were reviewed and analyzed. Fourteen patients (15.7%) had lymphomatous involvement based on BMB (BMB+), and 17 patients (19.1%) had the possibility of BM involvement on FDG-PET/CT (FDG-PET/CT+). Seventy-two patients (80.8%) had concordant results between BMB and FDG-PET/CT (seven patients were positive for both, and 65 patients were negative for both), but 17 patients (19.2%) had a discordant interpretation (seven patients were BMB+ and FDG-PET/CT-, and ten were BMB- and FDG-PET/CT+). Although BMB+ patients had an inferior 2-year EFS (37.0% vs. 79.8%, p?相似文献   

Development and validation of a clinical prediction rule for bone marrow involvement in patients with Hodgkin lymphoma

We developed a clinical prediction rule for bone marrow involvement (BMI) in Hodgkin lymphoma based on 826 patients and validated it in 654 additional patients. Independent prognostic factors for BMI were x1, B symptoms; x2, stage III/IV prior to bone marrow biopsy; x3, anemia; x4, leukocytes fewer than 6 x 10(9)/L; x5, age 35 years or older; and x6, iliac/inguinal involvement. Each factor was graded as x(i)=1, if present, or x(i)=0, if absent. A simplified score Zs=8x1+6x2+5x3+5x4+3x5+3x6-8 was assigned to each patient. The sensitivity, specificity, and positive and negative predictive value of this prediction rule was 97.8%, 51.5%, 10.6%, and 99.8%, respectively. In the validation group, they were 98.1%, 40.3%, 12.7%, and 99.6%. According to Zs value, 3 risk groups for BMI were defined: low risk (Zs<0, 44% of patients, 0.3% risk), standard risk (Zs, 0-9; 37% of patients; 4.2% risk), and high risk (Zs>or=10, 20% of patients, 25.5% risk). Patients with low risk (stage IA/IIA without anemia and leukopenia; stage IA/IIA, younger than 35 years, with either anemia or leukopenia but no inguinal/iliac involvement; and stage IIIA/IVA without any of these 4 risk factors) do not need bone marrow (BM) biopsy. Patients with standard risk should be staged with unilateral biopsy, but patients with high risk may benefit from bilateral biopsy.     

Bone marrow and peripheral blood leptin levels in lymphoproliferative diseases--relation to the bone marrow fat and infiltration

Leptin is a nonglycosylated protein produced mostly by adipocytes. The role ofleptin in body weight regulation through its anorectic effect in hypothalamus is very well known. Less known are other leptin effects such as the stimulation of hematopoesis and some parts of immunity system. The role of leptin in the pathogenesis of some malignant tumors is discussed. Only a little is known about bone marrow adipocyte leptin production. We examined leptin concentrations in the sera from peripheral blood and bone marrow, the percentage of bone marrow fat, the degree of bone marrow infiltration, the body mass index (BMI) in 42 patients with lymphoproliferative diseases. We found that bone marrow has significantly lower leptin levels (6,6+/-10,9 ng/ml) than peripheral blood (9,1+/-11,5 ng/ml) (p < 0.0001). Bone marrow and peripheral blood leptin levels have also a significant thin correlation (r = +0.91, p < 0.0001). Bone marrow (r = +0.55, p < 0.0005) and peripheral blood (r = +0.52, p < 0.0005) leptin concentrations are significantly correlated to BMI. Blood serum leptin (r = +0.46, p < 0.003) and bone marrow leptin (r = +0.40, p < 0.01) are related to the bone marrow fat percentage. In addition we found a negative correlation of blood serum leptin (r = -0.59, p < 0.0001) and bone marrow leptin (r = -0.42, p < 0.005) to bone marrow malignant infiltration. When we divided the patients into groups with bone marrow infiltration more than 10% and without or less than 10% infiltration, the first group had significantly lower peripheral blood (p < 0.001) and bone marrow (p < 0.02) leptin. We also confirmed a relation of bone marrow fat and infiltration (r = +0.49, p < 0.001). Our results suggest a relationship among leptin levels in blood or bone marrow and bone marrow infiltration in lymphoproliferative diseases. This fact needs further investigation and an evaluation of its application in clinical practice.     

Concordant but not discordant bone marrow involvement in diffuse large B-cell lymphoma predicts a poor clinical outcome independent of the International Prognostic Index

In diffuse large B-cell lymphoma (DLBCL), previous studies have suggested that, while concordant bone marrow (BM) involvement confers a poor prognosis, discordant BM involvement does not. Whether this correlation is independent of the non-Hodgkin lymphoma International Prognostic Index (IPI) was previously unknown. We reviewed all DLBCL case histories from 1986 to 1997 at our center with complete staging, IPI data, and follow-up. A total of 55 (11.2%) of 489 patients had BM involvement, including 29 with concordant involvement and 26 with discordant involvement. The 55 patients with BM involvement had a poor prognosis compared with the uninvolved BM group (5-year overall survival [OS], 34.5% versus 46.9%; log-rank P = .019). However, concordant involvement portended a very poor prognosis (5-year OS, 10.3%; P < .001), whereas discordant involvement did not (5-year OS, 61.5%, P value nonsignificant). Compared with the discordant subset, the concordant subset patients were older, had a higher serum lactate dehydrogenase level, and a significantly higher IPI. However, the poor survival associated with concordant BM involvement was independent of the IPI score (P = .002, Cox regression). We conclude that in patients with DLBCL, concordant but not discordant BM involvement confers a very poor clinical outcome. Furthermore, concordant BM involvement is an independent adverse prognostic factor.     

Bone marrow and peripheral blood involvement in mantle cell lymphoma

The peripheral blood smears, bone marrow aspirates and biopsies of 46 patients with mantle cell lymphoma were reviewed. The diagnosis of mantle cell lymphoma was established in all cases on extramedullary tissue samples using standard morphologic, phenotypic and molecular genetic criteria. 27/35 patients (77%) had circulating lymphoma cells (median 20% of all circulating white blood cells; range 5–90%) identified by morphology at some point during the course of their disease. No statistical difference in survival was detected in patients with or without peripheral blood involvement. Lymphoma was identified in bone marrow aspirate specimens from 33/40 patients (83%) and in bone marrow biopsy specimens from 39/43 patients (91%). The pattern of marrow biopsy involvement was nodular (31 cases; 82%), interstitial (19 cases; 50%), paratrabecular (17 cases, 45%) and diffuse (12 cases; 32%). Although the median survival of patients with ≥ 50% bone marrow involvement was 13 months, and the median survival of patients with ≤ 50% was 49 months, no statistically significant differences between these small subgroups were observed. Mantle cell lymphoma frequently involves the peripheral blood and bone marrow. Its appearance is distinctive but variable, and immunophenotypic studies as well as morphologic confirmation by a biopsy of tissue other than bone marrow is still required for diagnosis.     

18F‐FDG PET‐CT and trephine biopsy assessment of bone marrow involvement in lymphoma

The ability of positron emission tomography‐computerized tomography (PET‐CT) to accurately detect bone marrow involvement (BMI) has been suggested in Hodgkin lymphoma (HL) and diffuse large B‐cell lymphoma (DLBCL), but its abilities in other histologies is less established. The aim of this retrospective study was to confirm the role of PET‐CT in detecting BMI in DLBCL and HL, and to explore its usefulness in other subtypes. Of the 149 newly diagnosed patients, common subtypes included DLBCL, follicular lymphoma (FL) and HL. In DLBCL, the sensitivity and specificity of PET‐CT at diagnosis were 75% and 92%. In FL, the sensitivity and specificity of PET‐CT were 67% and 85% at diagnosis, and 73% and 89% at relapse. In HL, the sensitivity and specificity were 100% and 74%. PET‐CT was able to detect BMI in patients with negative biopsies. Most of the patients in which PET‐CT failed to identify BMI were already advanced stage by imaging. In this analysis, PET‐CT was highly accurate for detecting BMI at diagnosis in DLBCL and HL and highly specific in FL at diagnosis and relapse. Results also suggested the diagnostic advantage of PET‐CT over bone marrow biopsy in detecting BMI. Prospective evaluation is necessary and may eliminate biopsies in future patients.     

Contribution of flow cytometric immunophenotyping and bone marrow trephine biopsy in the detection of lymphoid bone marrow infiltration in non-Hodgkin's lymphomas

The bone marrow (BM) is a frequent site of involvement in non-Hodgkińs lymphomas (NHL) and evidence of an infiltrated BM may implicate different therapeutical regimens. Flow cytometric immunophenotyping of bone marrow aspirates now is included in the assessment of patients with NHL and used as an adjunct to morphologic evaluation in the staging of lymphoma. The aim of the study was to compare flow cytometric immunophenotyping of BM and paraffin section staining of BM biopsies in the marrow involvement of NHL. Cytometric immunophenotyping of bone marrow and immunohistochemical paraffin section staining of bone marrow biopsies in 53 B- and T-cell lymphoma patients were performed. We used the following fluorochrom conjugated monoclonal antibodies specific for: CD3, CD4, CD5, CD7, CD8, CD10, CD19, CD20, CD22, CD23, CD79B, FMC7 and Ig kappagamma light chain. Unilateral BM trephine biopsies were obtained in all cases, fixed, decalcified and paraffin-embedded. Morphologic marrow involvement by lymphoma was found in 24 cases; flow immunophenotyping identified 26 cases with NHL: morphology-positive/flow-positive (n=21), morphology positive/flow-negative (n=3), morphology-negative/flow-positive (n=4), and morphology-negative/flow-negative (n=23). The concurrence rate of BM trephine biopsy and flow cytometric immunophenotyping in evaluation of NHL bone marrow infiltration was 88.7%. Immunophenotyping of the bone marrow of NHL patients by flow cytometry is helpful for assessment of bone marrow infiltration, especially in B-cell disorders. Both trephine biopsies and flow cytometry are better than single investigation for detection of infiltration in NHL.     

Comparison of Bone Marrow Involvement with Bone Marrow Biopsy and PET–CT and Evaluation of Any Effects on Survival in Patients Diagnosed with Hodgkin and Non-Hodgkin Lymphoma

We aimed to demonstrate whether PET–CT can replace bone marrow biopsy in detecting bone marrow involvement in subtypes of lymphoma. In addition, we aimed to also reveal whether there is a difference between the mean survival of patients with bone marrow involvement via PET–CT or biopsy. A total of 276 newly diagnosed lymphoma patients who underwent bone marrow biopsy and PET–CT prior to the treatment were scanned retrospectively. Bone marrow biopsy was used as the standard method to investigate the presence of bone marrow involvement in PET–CT. The relationship between bone marrow involvement and mean survival was compared using both methods. Out of the 276 patients, bone marrow involvement was detected with PET–CT and with biopsy, respectively in 56 patients (20.2%) and in 78 patients (28.2%). In terms of PET–CT’s accuracy with respect to revealing bone marrow involvement, the highest rates were achieved respectively in diffuse large B cell lymphoma (DLBCL) (87.4%) and Hodgkin lymphoma (HL) (77.7%). In both the PET–CT and bone marrow biopsy methods, Overall Survival (OS) was found to be significantly shorter in patients with involvement than in patients without involvement (P: 0.001). PET–CT may replace bone marrow (BM) biopsy in detecting the bone marrow involvement in aggressive lymphoma subtypes such as DLBCL and HL. The presence of BM involvement at the time of diagnosis in both PET–CT and BM biopsy is associated with poor prognosis, and OS is short in this group.     

Magnetic resonance imaging for the detection of bone marrow involvement in malignant lymphoma

This study systematically reviewed the published data regarding the sensitivity of magnetic resonance imaging (MRI) compared with bone marrow biopsy as reference standard for the detection of bone marrow involvement in patients with malignant lymphoma. A systematic search for relevant studies was performed of the PubMed/MEDLINE and Embase databases. Two reviewers independently assessed the methodological quality of each study and the sensitivity of the included studies was calculated. The 11 included studies had moderate methodological quality. Sensitivity of MRI for the detection of bone marrow involvement ranged from 50% to 100%, with a median of 100%. MRI is probably sufficiently sensitive to rule out bone marrow involvement in patients with malignant lymphoma. However, a well-designed study with a large sample size is needed to confirm current results.     

Magnetic resonance imaging of bone marrow in lymphoproliferative disorders: correlation with bone marrow biopsy

In a prospective clinical study 10 normal volunteers and 30 patients with lymphoma--11 patients with Hodgkin's lymphoma and 19 patients with non-Hodgkin's lymphoma (11 low grade, 8 high grade)--were examined. Proximal femora, pelvis and lumbar spine were imaged with a 1.5 tesla superconducting MR imaging system (Siemens Magnetom). Areas of malignant infiltration in the bone marrow were clearly detected by visual and/or quantitative assessment. In most cases bone marrow involvement was demonstrated by both magnetic resonance imaging and bone marrow biopsies. However, in three of 30 patients magnetic resonance imaging showed evidence of lymphomatous involvement despite normal bone marrow histology. In one patient bone marrow cytology revealed malignant infiltration in the absence of MRI abnormalities. Thus, MRI is a sensitive method for detecting bone marrow infiltration by lymphoma.     

Polymerase chain reaction detection of cells carrying t(14;18) in bone marrow of patients with follicular and diffuse large B-cell lymphoma: the importance of analysis at diagnosis and significance of long-term follow-up

The t(14;18) is the most frequent chromosomal aberration observed in follicular lymphoma (FL), and is less frequent in diffuse large cell lymphoma (DLCL). The bcl-2/IgH rearrangement constitutes good target for polymerase chain reaction (PCR) detection that allows to find out one tumor cell in 100,000 normal cells. The PCR assay was used to detect bcl-2-rearranged cells in blood and bone marrow (BM) in 63 previously untreated patients with DLCL and in 53 patients with FL. Twenty five FL patients (47%) and 9 DLCL patients (14%) had PCR-detectable lymphoma cells in BM and peripheral blood. Minimal residual disease (MRD) was evaluated in 17 FL and 5 DLCL patients undergoing first-line chemotherapy. Three DLCL patients (60%) but only 1 FL (6%) patient achieved molecular response (PCR-negative status in BM). Two PCR bcl-2/IgH positive patients with FL were treated with rituximab (anti-CD20 antibody) and had no PCR-detectable lymphoma cells in BM after the therapy. Peripheral blood stem cells (PBSC) were harvested in 5 FL (1 PCR-negative) and in 2 DLCL (1 PCR-negative) patients. PCR-positive lymphoma cells contamined PBSC in all patients with BM PCR-positivity before harvesting. Five FL patients underwent autologous transplantation (AT). No bcl-2/IgH positive cells were detected in 4 patients (80%) at any point after AT. One patient achieved molecular response after rituximab treatment. All the patients are in CR 6, 22, 30, 31 and 42 months respectively, after AT. On the other hand, 4 FL patients in clinical complete remission, but with persistent PCR positivity in BM relapsed with median of 21 months (interval, 14-28 months) from the end of a first-line chemotherapy. Thus, the results show that PCR detection of the bcl-2/IgH rearrangement is a very useful method in evaluating the BM infiltration by lymphoma cells especially in the situation of MRD. Conventional chemotherapy did not eradicate bcl-2 positive cells in BM in most of lymphoma patients, but autologous transplantation or rituximab immunotherapy can induce molecular response in a significant proportion of them. Our results support the previous observations of the molecular response importance in view of better disease free and probably also overall survival.