Presence Of Bone Marrow Involvement Research Articles

Naked antibodies and antibody-drug conjugates: targeted therapy for childhood acute lymphoblastic leukemia.

The treatment of childhood acute lymphoblastic leukemia (ALL) has reached overall survival rates exceeding 90%. The present and future challenges are to cure the remainder of patients still dying from disease, and to reduce morbidity and mortality in those who can be cured with standard-of-care chemotherapy by replacing toxic chemotherapy elements while retaining cure rates. With the novel therapeutic options introduced in the last years, including immunotherapies and targeted antibodies, the treatment of ALL is undergoing major changes. For B-cell precursor ALL, blinatumomab, an anti-CD19 bispecific antibody, has established its role in the consolidation treatment for both high- and standard-risk first relapse of ALL, in the presence of bone marrow involvement, and may also have an impact on the outcome of high-risk subsets such as infant ALL and Philadelphia chromosome-positive ALL. Inotuzumab ozogamicin, an anti-CD22 drug conjugated antibody, has demonstrated high efficacy in inducing complete remission in relapsed ALL, even in the presence of high tumor burden, but randomized phase III trials are still ongoing. For T-ALL the role of CD38-directed treatment, such as daratumumab, is gaining interest, but randomized data are needed to assess its specific benefit. These antibodies are currently being tested in patients with newly diagnosed ALL and may lead to major changes in the present paradigm of treatment of pediatric ALL. Unlike the past, lessons may be learned from innovations in adult ALL, in which more drastic changes are piloted that may need to be translated to pediatrics.

Expression and Prognostic Value of PIK3CA, VEGF, IL-8, IL-10, and RIP2 in Diffuse Large B-Cell Lymphoma.

To explore clinical features and prognostic value of vascular endothelial growth factor (VEGF), interleukin (IL) 8, IL-10, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and receptor-interacting protein-2 (RIP2) in diffuse large B-cell lymphoma (DLBCL). A total of 68 DLBCL patients admitted to the Affiliated Hospital of Hebei Engineering University from January 2017 to June 2021 were included in this retrospective analysis. Serum VEGF was detected by enzyme-linked immunosorbent assay, serum IL-8 and IL-10 were detected by chemiluminescent enzyme immunoassay, and expression of PIK3CA and RIP2 in tumors was detected by immunohistochemistry. The correlation between clinical features of DLBCL and tumor-related index were analyzed. Cox regression was conducted to explore risk factors and hazard ratio. The serum level or expressions of VEGF, IL-8, IL-10, and RIP2 were significantly elevated with the increase of Ann Arbor Stage, International Prognostic Index (IPI) scores, Eastern Cooperative Oncology Group (ECOG) scores, serum lactate dehydrogenase (LDH) level, and the number of extranodal sites (all P < 0.05). Beside, these serum indexes were significantly higher in patients with the presence of extranodal involvement and germinal center B-cell (GCB), but significantly lower in patients with the presence of bone marrow involvement (all P < 0.05). Cox regression analysis for overall survival revealed that high expression of VEGF, high level of serum IL-8, serum IL-10, and RIP2, Ann Arbor Stage (III-IV), number of extranodal sites (>1), serum LDH level (≥245 U/L), IPI scores (3-5), ECOG scores (≥2), and bone marrow involvement were independent risk factors for the prognosis of DLBCL patients (all P < 0.05). The serum levels of VEGF, IL-8, and IL-10, as well as the expression of RIP2 and PIK3CA in tumor tissues, were highly correlated to clinical features of DLBCL, and high expression level of these indexes may have adverse effects for the prognosis of DLBCL patients.

Comparison of clinical and PET-derived prognostic factors in patients with non-Hodgkin lymphoma: a special emphasis on bone marrow involvement

In patients with non-Hodgkin lymphoma (NHL), we investigated F FDG PET/computed tomography (CT) parameters, clinical findings, laboratory parameters, and bone marrow involvement (BMI) status for predictive methods in progression-free survival (PFS) and overall survival (OS), and whether F FDG PET/CT could take the place of bone marrow biopsy (BMB). The performance of F FDG PET/CT (BMPET) was evaluated. The prognostic value of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), stage, international prognostic index (IPI) score, IPI risk, lactate dehydrogenase (LDH), B2 microglobulin, Ki67 proliferation index, and the presence of BMI was evaluated for OS and PFS. Kaplan-Meier curves were drawn for each designated cutoff value, and 5-year PFS and 7-year OS were evaluated using log-rank analysis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of BMPET and BMB to identify BMI were 69, 100, 86.1, 80, 100%, and 81.6, 100, 92.5, 89, 100%, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of BMPET in patients with Ki67- proliferation index >25% were all 100%. BMPET, IPI risk, MTV, and LDH were found to be independent prognostic predictors for PFS, whereas BMPET, SUVmax, and MTV for OS. Five-year PFS analysis estimated as follows: BMPET (+) = 22%, BMPET (-) = 80%, LDH ≤ 437 (U/L) = 86%, LDH > 437 (U/L) = 51%, MTV ≤ 56 (cm) = 87%, MTV > 56 (cm) = 49%, low IPI risk = 87%, intermediate IPI risk = 69%, high IPI risk = 25%. Seven-year OS analysis was found as: SUVmax ≤ 17.6 = 80%, SUVmax > 17.6 = 48%, MTV ≤ 56 (cm) = 84.4%, MTV > 56 (cm) = 45.8%, BMPET (-) = 72.5%, BMPET (+) = 42%. In the Ki-67 proliferation index > 25% group, F FDG PET/CT was able to differentiate BMI independently from NHL subgroups. We recommend using this method with large patient groups. MTV and BMPET were independent prognostic indicators for OS and PFS and may help to determine high-risk patients.

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.

Prognostic values and clinical implications of programmed cell death-ligand 1 (PD-L1), fork head transcription factor P-1 (FOXP-1) and signal transducer and activator of transcription-3 (STAT-3) expression in diffuse large B-cell lymphoma (DLBCL); an immunohistochemical study

ContextPD-L1 is an inhibitory ligand that functions as an essential immune checkpoint. FOXP-1 is a member of the FOXP family. STAT-3 plays a critical role in regulation of cell proliferation and survival. The detailed expression of the three markers together in DLBCL tissues and their prognostic value in patients with DLBCL were not fully investigated.Aim was to assess the expression of PD-L1, FOXP-1 and STAT-3 in diffuse large B-cell lymphoma (DLBCL) and to correlate their expression with the pathological findings, prognostic parameters and clinical implications of patients.MethodsPD-L1, FOXP-1 and STAT-3 were assessed in DLBCL tissues derived from 50 patients using immunohistochemistry. Patients were followed up for 3 years for response to therapy progression, recurrence and survival.ResultsHigh PD-L1 expression was associated with bone marrow involvement (p = 0.004), extra-nodal involvement (p = 0.006) and advanced stage (p = 0.003). High FOXP-1 expression was associated with presence of bone marrow involvement and high risk group (p < 0.001). High STAT-3 expression was associated with older age of the patient (p < 0.001), presence of bone marrow involvement (p = 0.002), extra-nodal involvement (p = 0.009), and high risk group (p = 0.005). High expression of PD-L1, FOXP-1 and STAT-3 was related to poor response to therapy, poor OS rate and RFS rates (p < 0.001).ConclusionHigh expression of PD-L1, FOXP-1 and STAT-3 was related poor prognosis in DLBCL patients.

Bone Marrow Biopsy Is Still Indispensable for Evaluating Bone Marrow Involvement in DLBCL Patients Even in the PET/CT Era

Background: Initial staging by positron emission tomography/computed tomography (PET/CT) is recommended for lymphoma of fluorodeoxyglucose (FDG)-avid histology, such as diffuse large B-cell lymphoma (DLBCL). Although both PET/CT and bone marrow biopsy (BMB) are usually performed to determine the bone marrow involvement in DLBCL, whether PET/CT alone is sufficient remains controversial. While previous reports discussing this point have used data based on medical records, here we performed a systematic review of untreated DLBCL patients, for whom a radiologist and a hematopathologist separately performed blind reviews. Methods: The subjects had DLBCL diagnosed between 2008 and 2017 for which both PET/CT and BMB were performed for staging before initiation of treatment. We excluded cases in which BMB specimens were qualitatively and/or quantitatively insufficient to determine the presence or absence of bone marrow involvement. To exclude follicular lymphoma, we did not include patients whose diagnostic specimens of lymphoma included any degree of nodular growth pattern. All PET/CT scans were performed in a single institution. In PET/CT, cases with score 4 or 5 in the Deauville criteria in bone marrow were classified as positive. In the review of BMB, we used both hematoxylin-eosin staining and CD20 immunostaining specimens in all cases to determine the involvement. We treated the presence of bone marrow involvement by BMB as a reference, and the involvement type was classified as either concordant or discordant pattern. Survival curves were compared by the log-rank test. A P-value less than 0.05 was considered to indicate a significant difference. Results: The study included 87 untreated patients with DLBCL (82 DLBCL, NOS; 3 intravascular large B-cell lymphoma; and 2 primary mediastinal large B-cell lymphoma), comprising 46 males and 41 females. The median age at the time of diagnosis was 71 (range, 19 to 87 years). The number of positive cases in PET/CT and BMB was 17 (20%) and 24 (28%), respectively (Table). Nine (10%) cases had both positive results. Among BMB-positive cases, there were18 concordant and 6 discordant involvements. When considering BMB results as a reference, PET/CT showed 38% sensitivity and 87% for specificity. The positive and negative predictive values were 53% and 79%, respectively. In 61 patients initially treated with R-CHOP, there was no significant difference in progression-free survival (PFS) between positive and negative cases in PET/CT (P = 0.16) , but PFS was significantly worse for BMB-positive cases than BMB-negative cases (P = 0.03). Conclusion: BMB is still mandatory in patients with untreated DLBCL and predicts outcome in the era of PET/CT. Routine CD20 immunostaining might be helpful in detecting lymphoma involvement in BMB specimens. DisclosuresNo relevant conflicts of interest to declare.

Prognostic and Clinicopathological Value of Survivin in Diffuse Large B-cell Lymphoma

Up to date, survivin, a well-known inhibitor of apoptosis, has attracted considerable attention as a potential biomarker and therapeutic target in diffuse large B-cell lymphoma (DLBCL). Nevertheless, there still remains no consensus on heterogeneous results. Herein, a meta-analysis was performed to clarify a convincing significance of survivin status on prognosis and clinicopathology of DLBCL patients.Eligible studies were identified by searching Medline, Embase, Scopus, CNKI, and Wanfang databases (last updated on November 30, 2014). Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Heterogeneity and sensitivity were also analyzed. Moreover, Begg, Egger test, and funnel plots were applied to evaluate the publication bias.We finally included 17 eligible studies with the total number of 1352 patients in the meta-analysis. The pooled results showed that positive survivin expression in DLBCL was associated with inferior overall survival (OS) (HR: 1.880, 95% CI: 1.550-2.270) in patients. Moreover, a significant association was revealed between survivin expression and advanced clinical stage (III + IV) (OR: 0.611, 95% CI: 0.452-0.827), higher International Prognosis Index (IPI) score (Score 3-5) (OR: 0.559; 95% CI: 0.410-0.761), elevated serum lactic dehydrogenase (LDH) (OR: 0.607, 95% CI: 0.444-0.831), presence of bone marrow involvement (OR: 2.127, 95% CI: 1.154-3.921) together with reduced complete remission (CR) rate (OR: 0.478, 95% CI: 0.345-0.662).The results suggest that survivin could be a useful prognostic biomarker, and a promising target for DLBCL therapeutic intervention. Considering limited HR data adjusted for standard prognostic variables could be retrieved, future high-quality studies will be needed in evaluating the independent prognostic value of survivin expression in DLBCL.

Hematologic findings predictive of bone marrow disease in dogs with multicentric large-cell lymphoma.

Evaluation of the bone marrow is needed for complete staging in dogs with multicentric large-cell lymphoma, but is often omitted in clinical practice. The objective was to determine if routine peripheral blood findings, including microscopic evaluation of blood smears, can predict the presence of bone marrow involvement in dogs with lymphoma. Hematologic data including evaluation of blood smears and bone marrow aspirates from 107 dogs newly diagnosed with large-cell lymphoma were retrospectively evaluated. Neoplastic lymphocytes were identified based on cell size, nuclear size, chromatin pattern, and the presence of nucleoli. Positive specimens were defined as having ≥10% neoplastic lymphocytes. Two groups were established based on the presence or absence of lymphoma in the bone marrow. Variables (positive blood smear, HCT, platelet count, and total and differential WBC counts) were evaluated to determine if they were predictive of bone marrow involvement using univariate and multivariate logistic models. Thrombocytopenia and the presence of >10% neoplastic lymphocytes on blood smears were identified as significant variables for predicting the presence of bone marrow involvement. When considered independently, either a positive blood smear or thrombocytopenia had low sensitivity (60%) and moderate specificity (89% and 87%, respectively). Sensitivity increased when these variables were evaluated together (80%). In dogs with multicentric large-cell lymphoma, thrombocytopenia or the presence of neoplastic lymphocytes in circulation is suggestive of bone marrow involvement, but not definitive. Normal peripheral blood findings do not exclude the possibility of lymphoma in the bone marrow.

FDG PET/CT for the detection of bone marrow involvement in diffuse large B-cell lymphoma: systematic review and meta-analysis

To systematically review and meta-analyse published data on the diagnostic performance of (18)F-FDG PET/CT in detecting bone marrow involvement in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). PubMed/MEDLINE and Embase were systematically searched for relevant studies. The methodological quality of each study was assessed. Sensitivities and specificities of FDG PET/CT in individual studies were calculated and meta-analysed with a random effects model. A summary receiver operating characteristic curve (sROC) was constructed with the Moses-Shapiro-Littenberg method. Weighted summary proportions of discrepancies between the FDG PET/CT and (blind) bone marrow biopsy (BMB) results among all patients were calculated. Seven studies, with a total of 654 patients with newly diagnosed DLBCL, were included. Overall, the quality of the included studies was moderate. The sensitivity and specificity of FDG PET/CT for detecting bone marrow involvement ranged from 70.8% to 95.8% and from 99.0% to 100%, with pooled estimates of 88.7% (95% confidence interval, CI, 82.5-93.3%) and 99.8% (95% CI 98.8-100%), respectively. The area under the sROC curve was 0.9983. The weighted summary proportion of FDG PET/CT-negative patients with positive BMB findings among all patients was 3.1% (95% CI 1.8-5.0%) and the weighted summary proportion of FDG PET/CT-positive patients with negative BMB findings among all patients was 12.5% (95% CI 8.4-17.3%). FDG PET/CT is accurate and complementary to BMB for detecting bone marrow involvement in patients with newly diagnosed DLBCL. A negative FDG PET/CT scan cannot rule out the presence of bone marrow involvement, but positive FDG PET/CT findings obviate the need for BMB for the detection of bone marrow involvement in these patients.

A Look in the Mirror

A Look in the Mirror

Mantle cell lymphoma: clinicopathologic features and prognostic factors of 102 cases occurring in Chinese patients

To study the clinicopathologic features and prognostic factors of Chinese patients with mantle cell lymphoma. One hundred and two cases of mantle cell lymphoma occurring in Chinese patients were studied by light microscopy and immunohistochemistry. The follow-up information was also analyzed. The cases were classified as mantle zone, nodular or diffuse patterns and as typical or blastoid variants. Age, Ann-Arbor staging, B symptoms, hematologic parameters, histologic variants, mitotic index and immunophenotype were assessed for possible prognostic implication. The median age of the patients was 59 years (range: 30 to 79 years) and the male-to-female ratio was 2.92:1. Seventy-one patients (87.65%) presented with advanced stage disease (Ann Arbor stage III to IV). B symptoms were present in 45.45% of patients. The commonest site of involvement was lymph node (100%). The other involved sites included bone marrow (64.44%), spleen (63.16%), Waldeyer's ring (31.25%), peripheral blood (29.41%), liver (22.64%) and gastrointestinal tract (14.71%). All cases expressed B-cell markers but were negative for T-cell marker. Majority of cases were positive for cyclin D1 (94.12%) and CD5 (71.43%). Blastoid variant accounted for 24.51% of cases. Amongst the 68 cases with follow-up data available, the median survival was 10 months. Parameters associated with shorter survival included diffuse pattern, blastoid variant, high mitotic index, high proliferative activity and presence of bone marrow involvement. The clinicopathologic features and prognostic factors of mantle cell lymphoma occurring in Chinese are similar to those in Caucasians. Diffuse pattern, blastoid variant, high mitotic index, high proliferative activity and involvement of bone marrow indicate poor prognosis.

The utility of 18-F-fluorodeoxyglucose positron emission tomography in evaluation of bone marrow involvement by non-Hodgkin lymphoma (NHL)

8077 Introduction: In NHL, the anatomic extent of the disease is an important factor influencing the overall survival. Clinically, NHLs are classified as indolent, aggressive, or highly aggressive. Bone marrow (BM) involvement is a sign of extensive disease, and iliac crest (IC) BM biopsy (BMB) is the established method for the detection of BM infiltration. However, IC BMB is associated with a high rate of false- negative result. We assess the ability of 18F-FDG PET scan to ascertain the presence of BM involvement in NHL. Methods: We retrospectively reviewed charts from January 2002 through November 2006 of histologically proven NHLs. 87 patients (pts) were eligible for our study (38 males, 49 females; age range 42–81 years). All pts were examined by whole-body 18F-FDG-PET scan for initial staging, and all had unilateral posterior IC BMB. BM involvement was established following the result of 1) unilateral posterior IC BMB, and 2) image-guided BMB following positive 18F-FDG-PET scan in selected patients. Results: Among the PET+ / IC BMB- group, 3 pts had a positive CT-scan guided BMB at the site of involvement detected by the 18F-FDG-PET scan (2 from the humerus,1 from the femur); the remaining 7 pts did not have a site-directed biopsy. Our data demonstrate an overall sensitivity of 0.76 for the PET scan detecting BM involvement in all pts and specificity of 0.88. We point out that the 0.88 specificity may be spuriously low, this is a result of the fact that of the 10 PET+ / IC BMB- pts 7 have not had directed biopsy to the site of involvement detected by the18F-FDG- PET-scan. Further analysis revealed no significant difference between the sensitivity (P = 0.21) and specificity (p = 0.99) between I- NHL and A/HA- NHL groups. Conclusion: 18F-FDG-PET scan shows potential to detect BM involvement in NHL. In particular, image-guided repeat BMB may be considered in pts with negative initial IC BMB, whose 18F-FDG-PET scan demonstrates BM involvement in a different site. No significant financial relationships to disclose. [Table: see text]

The prognostic impact of bone marrow involvement in patients with diffuse large cell lymphoma varies according to the degree of infiltration and presence of discordant marrow involvement

The prognostic significance of marrow involvement in diffuse large cell lymphoma (DLCL) is controversial. Factors that that have been reported to influence prognosis include the pattern and extent of marrow infiltration and histological discordance between the primary site and the bone marrow. Bone marrow biopsies from 172 patients with newly diagnosed DLCL entered in two consecutive trials of the Australasian Leukaemia and Lymphoma Group were analyzed. Progression-free (PFS) and overall survival (OS) were calculated according to the absence or presence of bone marrow involvement (BMI), the extent of lymphomatous infiltration and the presence of histological discordance between the primary site and the bone marrow. Of 172 patients with DLCL accrued between 1982 and 1990, who were treated with CHOP or CHOP-like regimens, 47 (27%) demonstrated marrow involvement on examination of multiple levels. Seventy two percent (34/47) of patients had discordant marrow involvement (<50% large cells) and 28 had minimal (<10%) involvement; these latter patients with minimal marrow involvement (<10%) had similar PFS & OS to the 113 patients without involvement. Within the group of 47 patients with marrow involvement, an increasing percentage of BM involvement was significantly associated with an increasing percentage of concordant histology and a decreasing PFS & OS. Minimal BMI, seen in the majority of patients with DLCL with marrow infiltration, appears not to influence the PFS & OS. However, an increasing degree of marrow involvement is associated with an increasing component of large cells and a poorer prognosis in DLCL patients, independent of other risk factors.

Can [18F]fluorodeoxyglucose positron emission tomography imaging complement biopsy results from the iliac crest for the detection of bone marrow involvement in patients with malignant lymphoma?

To assess the usefulness of [18F]fluorodeoxyglucose positron emission tomography in the detection of bone marrow involvement in malignant lymphoma, and its impact in clinical management. One hundred and six consecutive patients with a confirmed diagnosis of lymphoma, referred for staging or restaging of Hodgkin's lymphoma (n=18) or non-Hodgkin's lymphoma (n=88), were reviewed retrospectively. A positron emission tomography scan and bone marrow biopsy of the iliac crest were performed in all patients. The assessment of bone marrow involvement by lymphoma was confirmed by histology and/or progression of bone marrow lesions in clinical follow-up. In 28 of 106 patients, bone marrow involvement was found. Positron emission tomography was more sensitive (86%) than bone marrow biopsy (57%). Positron emission tomography and bone marrow biopsy were concordant by positive correlation in 12 of 28 cases (43%) and by negative correlation in 77 of 78 cases (99%). Ten cases of non-Hodgkin's lymphoma and two cases of Hodgkin's lymphoma with positive positron emission tomography results and an initial negative bone marrow biopsy showed clinical progression of the bone marrow lesions and/or subsequent positive histology. These were considered as false-negative results for bone marrow biopsy. In seven of the 12 positive cases with negative bone marrow biopsy, positron emission tomography uptake distant from the site of the biopsy was seen. In four cases of follicular lymphoma, the bone marrow biopsy was positive and the positron emission tomography scan was normal. Positron emission tomography and bone marrow biopsy are complementary in assessing the presence of bone marrow involvement in patients with malignant lymphoma. In our series, positron emission tomography was more sensitive than bone marrow biopsy in Hodgkin's and non-Hodgkin's lymphoma, except in follicular lymphoma.

Tositumomab and iodine I 131 tositumomab: Efficacy and safety in 141 patients (pts) with previously untreated low-grade (LG) non-Hodgkin’s lymphoma (NHL)

6560 Background: Tositumomab and Iodine I 131 Tositumomab (the BEXXAR Therapeutic Regimen, hereafter Iodine I 131 Tositumomab) yields high rates of durable and complete (CR) responses in pts with relapsed/refractory LG NHL. Methods: The efficacy and safety of this regimen was reviewed for 141 pts with previously untreated LG NHL in 3 studies: 76 pts receiving Iodine I 131 Tositumomab as stand-alone therapy, 35 pts receiving an abbreviated regimen of 3 cycles of fludarabine followed by Iodine I 131 Tositumomab, and 30 pts receiving 6 courses of CVP followed by Iodine I 131 Tositumomab. Investigator efficacy assessments were used. All responses had to be confirmed by a subsequent response ≥4 weeks later. Median follow-up was 61 mo (range, 8–101 mo). Results: Median age: 49 yr (range, 23–82 yr); median time from NHL dx: 8 mo; stage III/IV: 99%; tumor diameter ≥5 cm: 49%; bone marrow involvement: 55%. Overall response rate was 95% (95% CI: 90%, 98%); CR rate was 77% (95% CI: 69%, 84%). Median progression-free survival (PFS) was 6.1 yr. Only the presence of bone marrow involvement was associated with shorter PFS. Infusions were well tolerated (rate adjustments in only 4% of infusions). Hematologic toxicity was regimen dependent; no pts in the Iodine I 131 Tositumomab single agent study received supportive care vs 28% in the Iodine I 131 Tositumomab combination regimens studies. Nonhematologic non-serious AEs were significantly more frequent in the single agent study (excluding chemotherapy period in combination studies). Overall only 4% of pts had a drug-related serious AE after Iodine I 131 Tositumomab. Elevated HAMA levels occurred in 63% of the pts in the single agent study vs 3% of pts in the combination studies. Hypothyroidism (elevated TSH) occurred in 9% of pts in the single agent study and 10% in the combination studies. Two pts (both from combination studies) developed MDS/AML, with an overall annualized incidence of 0.3%/yr. Conclusions: Iodine I 131 Tositumomab stand-alone therapy and in combination with chemotherapy was well tolerated and resulted in prolonged PFS in pts with previously untreated LG NHL. Randomized comparative studies should be performed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline

Clinical Factors Predictive of Bone Marrow Involvement in Hodgkin's Disease

The role of bone marrow biopsy in the staging of Hodgkin's disease is undergoing reevaluation. We have studied the relationship of clinical factors to the presence of bone marrow involvement in 130 previously untreated patients with Hodgkin's disease. The presence of fever, spleen enlargement, anemia, leukopenia, poor performance status and poor histologic subgroups were positively correlated with the presence of bone marrow involvement in the univariate analysis. In the multivariate analysis, only fever, spleen involvement, leukopenia and poor histologic subgroups were significant. The predictive value of the absence of fever in regard to the absence of bone marrow involvement was 98%. The likelihood of bone marrow involvement in the absence of all four significant factors was only 0.05%. Patients without these clinical factors should probably not be submitted to a bone marrow biopsy as part of the staging procedures performed in Hodgkin's disease.

Bone marrow involvement in Hodgkin's disease: an analysis of 135 consecutive cases. German Hodgkin's Lymphoma Study Group.

To describe the incidence of primary bone marrow involvement (BMI) in Hodgkin's disease (HD) and its correlation with clinical and laboratory features present at diagnosis, and to evaluate the prognostic relevance of BMI. Between 1983 and 1991, 2,307 patients with HD were treated according to two trial generations (HD1-3 and HD4-6) of the German Hodgkin's Lymphoma Study Group (GHSG). One hundred thirty-five cases of primary BMI were observed. The incidence of BMI was 4.8% in the HD4-6 study generation, which included all stages. Among stage IV patients, 32% had BMI. Among those with BMI, other organs were also involved in 33%. Among all patients, the presence of BMI was significantly associated with B symptoms, lymph nodes on both sides of the diaphragm, mixed cellularity histologic subtype, leukocytopenia, anemia, thrombocytopenia, lactate dehydrogenase (LDH) level more than 400 U/L, and erythrocyte sedimentation rate (ESR) more than 40 mm/h. BMI was negatively correlated with a large mediastinal tumor (3.7% v 20.0% in non-BMI cases). Eighty-seven of 108 (81%) assessable patients with BMI achieved a complete remission (CR). This compares favorably with the overall CR rate in all stage IIIB/IV patients. Among stage IV patients, BMI has no prognostic relevance with regard to freedom from treatment failure and overall survival. Twenty-one patients with BMI relapsed after having achieved a CR. Only five of these (24%) again had a positive bone marrow biopsy. The prognosis of patients with BMI is not worse than the prognosis of other advanced-stage HD patients. BMI alone does not define a special high-risk group in which a different treatment approach is indicated.

Bone marrow involvement in anaplastic large cell lymphoma. Immunohistochemical detection of minimal disease and its prognostic significance.

Bone marrow involvement by anaplastic large cell anaplastic large cell (ALC) lymphoma can be difficult to detect on routine morphologic examination alone. In a series of 42 patients with ALC lymphoma, the authors analyzed: (1) the usefulness of a limited panel of monoclonal antibodies directed against CD30 (Ber-H2, HRS4) and epithelial marrow involvement on routinely processed biopsy specimens; and (2) the prognostic significance of bone marrow involvement as detected on both morphologic and immunohistochemical grounds. On conventional examination, 17% of the patients were found to have bone marrow involvement at diagnosis. However, after immunohistochemical analysis, occult malignant cells were detected in 23% of the patients with negative bone marrow biopsy on routine histology. The low percentage of positive cases on routine morphologic examination compared to immunohistochemical examination was related to: (1) the scarcity of neoplastic cells which were scattered among hematopoietic cells; (2) the difficulty of distinguishing malignant cells from immature hematopoietic elements; and (3) the absence of alteration of the reticulin network. The authors observed a significant association between marrow infiltration and the presence of hematologic abnormalities (mostly anemia or cytopenias) at diagnosis, both in children and adult patients. More importantly, a significant lower survival was seen in patients with bone marrow involvement compared to those without bone marrow involvement. Immunohistochemistry with anti-CD30 and anti-EMA antibodies should be performed systematically in bone marrow biopsies from patients with ALC lymphoma to reliably identify the presence of bone marrow involvement that appears to carry a poor prognosis.

Haemopoietic reconstitution after autologous blood stem cell transplantation in patients with malignancies: a multicentre retrospective study

A retrospective study was undertaken to evaluate the efficacy of autologous blood stem cell transplantation (ABSCT) in terms of haemopoietic reconstitution after ablative chemotherapy or chemo-radiotherapy. 55 patients with malignancies, observed in four Italian institutions from January 1987 to June 1991, were eligible for evaluation. This series included 19 non-Hodgkin's lymphoma, 11 multiple myeloma, nine ovarian cancer, seven Hodgkin's disease, seven non-lymphocytic leukaemia, one acute lymphoblastic leukaemia, one neuroblastoma. 522 PBSC collections were performed on 55 patients. Following ABSCT, the rate of engraftment was positively related to the dose of CFU-GM infused and negatively to the presence of bone marrow involvement at conditioning. 48 patients out of 55 transplanted (87%) had rapid, complete and sustained engraftment. Three patients (5%) died of transplant-related complications. Considering that 60% of the patients in this series were in partial remission or in progressive disease at the time of ABSCT, we conclude that ABSCT is a safe approach for the use of ablative conditioning therapy in patients with a wide scope of malignancies, provided that a large number of CFU-GM have been collected after mobilizing treatment.

Prognostic Factors in Dogs with Lymphoma and Associated Hypercalcemia

Lymphoma and hypercalcemia were diagnosed in 37 dogs. Twenty-six of the dogs received chemotherapy. The association between some prognostic factors including clinical stage of disease, illness status, presence of bone marrow involvement, and presence of an anterior mediastinal mass and remission duration and survival time was evaluated. Statistical analysis of the prognostic factors showed that the presence of an anterior mediastinal mass had an adverse effect on remission duration (P less than 0.03). Calcium concentration was not significantly related to any of the prognostic factors evaluated. Dogs that received chemotherapy were more likely to be self-supporting than the dogs that were not treated (P less than 0.005). However, initial illness status was not significantly related to remission duration or survival time in the 26 dogs that were treated. Six dogs (25% of dogs treated) survived longer than 14 months. Five of these dogs were female. Overall mean and median remission times were 10.4 and 6 months, respectively.