Bone Marrow Positive Patients Research Articles

Comparative Role of 18F-DOPA PET/CT and 131I-MIBG Scintigraphy in Neuroblastoma and Application of Curie and SIOPEN Scoring Systems in 18F-DOPA PET/CT.

Neuroblastoma (NB) is childhood's most common extracranial solid malignancy. We have compared two imaging modalities, 131I-MIBG and 18F-DOPA PET/CT, to evaluate NB. Also, feasibility of the application of standardised scoring systems, SIOPEN and Curie scoring systems, in 18F-DOPA PET/CT was explored. Patients with histopathology-proven NB underwent 131I-MIBG (planar and SPECT/CT) and 18F-DOPA PET/CT scans, as per standard imaging protocols. Duration between scans ranged from 1 to 30days (median = 8days). Number of lesions in Curie and SIOPEN scoring systems applied on both modalities was compared. Forty-six patients were included (M:F = 29:17) with a median age of 36months. Both 131I-MIBG and 18F-DOPA scans were positive in 39 patients and negative in four patients. 18F-DOPA PET/CT was positive in additional three patients, in which 131I-MIBG was negative (p = 0.25). Overall, 18F-DOPA identified significantly greater number of lesions than 131I-MIBG, especially metastatic skeletal lesions (p < 0.05). Significant difference was observed between Curie scores in the two modalities, unlike SIOPEN scores. However, when the cut-off age of 18months was taken, no significant difference was seen in either of the scoring systems in both the scans (p > 0.05). CS and SIOPEN scores were significantly higher in bone marrow-positive patients. 18F-DOPA PET/CT detected more lesions than 131I-MIBG but had little impact on staging of the disease. For evaluation of NB, both scans can be used interchangeably as per the availability. Furthermore, both SIOPEN and Curie scoring systems, standardised for MIBG, can also be used to semi-quantify disease extent in 18F-DOPA PET/CT. The online version contains supplementary material available at 10.1007/s13139-022-00762-6.

Detection and clinical relevance of hematogenous tumor cell dissemination in patients with ductal carcinoma in situ

Hematogenous tumor cell dissemination is a crucial step in systemic disease progression and predicts reduced clinical outcome in breast cancer patients. Only invasive cancers are assumed to shed tumor cells into the bloodstream and infiltrate lymph nodes. However, recent studies revealed that disseminated tumor cells (DTCs) may be detected in bone marrow (BM) of patients with preinvasive lesions, i.e., ductal carcinoma in situ (DCIS). The purpose of this analysis was to examine the incidence and clinical value of DTC detection in a large series of patients with pure DCIS. 404 patients treated for DCIS at the University Hospital Tuebingen, Germany were included into this analysis. BM was analyzed by immunocytochemistry (pancytokeratin antibody A45-B/B3) using ACIS system (Chromavision) according to the ISHAGE evaluation criteria. Sentinel nodes were analyzed in 316 patients by step sectioning and hematoxylin-eosin staining. DTCs were detected in 63 of 404 patients (16 %). No correlation was observed between BM status and tumor size, grading, histology or Van Nuys prognostic index. In two cases, metastatic spread into lymph nodes was observed; isolated tumor cells were found in one patient. After a median follow-up of 45 months (range 3-131 months), 3 % of BM positive patients died compared to 1 % of BM negative patients (p = 0.254). Relapse of any kind was observed in 7 % of patients with DTCs vs. 5 % of patients without DTCs (p = 0.644). The differences in overall (p = 0.088) and disease-free survival (p = 0.982) calculated by log-rank test were not statistically significant. Tumor cell dissemination may be detected in patients diagnosed with DCIS. Whether these cells disseminate from real preinvasive mammary lesions or represent the earliest step of microinvasion, remains unclear. A longer follow-up may be necessary to accurately assess clinical value of these cells in DCIS patients.

Impact Of Bone Marrow Involvement On Outcome Of Young Patients With High-Risk Diffuse Large B-Cell Lymphoma (DLBCL) Treated In The Phase III Randomized Trial (DLCL04) With Rituximab Dose-Dense Chemotherapy Followed By Intensified High-Dose Chemotherapy and Autologous Stem Cell Transplantation (HDC+ASCT) Or Standard Rituximab Dose Dense Chemotherapy: A Study of The Fondazione Italiana Linfomi (FIL)

IntroductionThe role of bone marrow (BM) involvement as prognostic factor in untreated young patients with diffuse large B-cell lymphoma at poor prognosis is still a matter of debate. Recent data showed an adverse prognostic role of BM involvement in DLBCL including patients both at low and high IPI score (Sehn L et al, J Clin Oncol 2011). On this basis, FIL analyzed the impact of BM involvement in the prospective randomized phase III trial DLCL04 (Vitolo U et al, Blood, ASH annual Meeting 2012) that included only young patients at high-risk age-adjusted IPI (aa-IPI) score 2 or 3. Patients and MethodsInclusion criteria were: age 18-65; untreated DLBCL or follicular grade IIIb; aa-IPI score 2 or 3. Patients were stratified according to aa-IPI and randomized at diagnosis to receive: R-CHOP14 x 8 cycles; R-MegaCHOP14 (1200 mg/sqm Cyclophosphamide, 70 mg/sqm Doxorubicin, standard dose Vincristine and Prednisone) x 6; R-CHOP14 x 4 + R-HDC (Rituximab + High Dose Cytarabine + Mitoxantrone + Dexamethasone) followed by BEAM and ASCT; R-MegaCHOP14 x 4 + R-HDC + BEAM and ASCT. BM biopsy and aspirate were mandatory at diagnosis; at the end of treatment, BM assessment was mandatory only in case of positivity at baseline. BM involvement was defined as concordant if marrow was involved by large B-cell and discordant if involved by small B-cells. Flow cytometry, immunohistochemistry, and/or molecular studies were utilized to confirm a clonal B-cell population. ResultsFrom June 2005 to September 2010, 399 patients were randomized to receive: 199 R-HDC+ASCT and 200 R-dose-dense chemotherapy without ASCT. All patients were evaluable for analysis. BM involvement was reported in 84 patients (21%): 39 (20%) in the R-HDC+ASCT group and 45 (22%) in the R-dose-dense chemotherapy group. Pattern of involvement was: concordant in 63 patients, discordant in 14 and not specified in 7 patients. Patients with BM involvement (BM positive: 84) compared to those without BM involvement (BM negative: 315) were significantly older (median age 53 years vs 47 years, p<.001) and at higher aa-IPI score (aa-IPI 3: 36% vs 24%, p .024); whereas other clinical characteristics were well balanced between the two groups (ECOG PS >1 43% vs 45%, bulky 25% vs 33%, extranodal sites > 1 26% vs 33%, LDH higher than normal value 93% vs 89%). With a median follow-up of 49 months, 3-year PFS for the whole series of 399 patients enrolled in the trial was: 67% (95% CI: 62-72). Three-year PFS was significantly worse in BM positive vs. BM negative: 46% (95% CI:35-56%) vs. 73% (95% CI:67-77%) p<.001 (Figure 1). In a Cox-model for PFS including type of treatment (ASCT vs no-ASCT, RCHOP vs R-MegaCHOP), age, gender, aa-IPI, performance status, histology and BM involvement, the adverse prognostic impact of BM involvement was maintained with an adjusted Hazard Risk (aHR) of 2.22 (95% CI:1.54-3.22, p<.001).Three-year OS rates in BM positive vs. BM negative were: 65% (95% CI:53-74%) vs. 83% (95% CI:78-87%) with an aHR 1.94 (95% CI:1.23-3.05; p=.004). The adverse prognostic impact of BM involvement on PFS was not affected by the type of treatment and the application of HDC+ASCT: 3-year PFS in BM positive patients treated with R-dose-dense chemotherapy 42% (vs. 69% BM negative) with an aHR of 2.19 (95% CI: 1.35-3.54, p<.001); 3-year PFS in BM positive patients treated with HDC+ASCT 51% (vs. 77% BM negative ) with an aHR of 2.27 (95% CI:1.30-3.97, p<.004). We further analyzed the prognostic impact of the pattern of BM involvement (concordant vs discordant). With the limits of small sample size of the discordant group, concordant BM involvement maintained an adverse prognostic impact on PFS whereas discordant involvement did not affect PFS: in a Cox-model assuming BM negative as reference, the risk of progression was significantly increased in the concordant involvement group with an aHR of 2.48 (95% CI: 1.68-3.67, p<.001) and not affected by discordant involvement (aHR 1.05; 95% CI:0.41-2.71, p=.916). [Display omitted] ConclusionsBone marrow involvement, namely concordant pattern, is a strong adverse predictor of outcome in young patients with untreated DLBCL at poor prognosis treated with R-chemotherapy regardless of intensification with HDC+ASCT. New treatment approaches are needed for these high-risk patients at poor prognosis. Disclosures:Vitolo:Roche: Speakers Bureau; Takeda: Speakers Bureau; Celgene: Speakers Bureau.

Epithelial-mesenchymal transition as a mechanism for the progression of breast carcinoma

Epithelial-mesenchymal transition (EMT) is a major process controlling multiple events during development. EMT has been conserved throughout evolution to control morphogenetic events, such as the formation of the three primary germ layers during gastrulation. Most interestingly, signal transduction pathways have been remarkably conserved in many different species. EMT pathways are also tightly connected to determination and differentiation programmes, and are reactivated in adult tissues following injury or exposure to toxic agents. EMT is likely to operate during the early stages of carcinoma invasion that lead to blood or lymph vessel intravasation. Mesenchymal-like carcinoma cells undergo a mesenchymal-to-epithelial transition in distant sites from the primary tumour and eventually become micrometastatic. We have characterised bone marrow micrometastases from breast cancer patients and found that the detection of micrometastatic carcinoma cells was associated with poorer distant metastasis-free survival, local relapse-free survival, and overall survival. Despite high rates of adjuvant systemic treatment and breast irradiation in this series, disseminated carcinoma cells remain a prognostic factor, in favour of the resistance to treatment of locally or distant disseminated cancer cells in bone marrow-positive patients. In addition, we detected micrometastatic carcinoma cells in patients with T1 tumours, suggesting that dissemination occurs much earlier during tumour progression than is generally accepted. Thus, bone marrow micrometastases should become a very useful prognostic indicator for relapse, and an excellent surrogate marker for patient's response to treatment. The mesenchymal-like state of carcinoma confers stemness, protection from cell death, escape from immune response and, most importantly, resistance to conventional and targeted therapies. Current strategies based on the EMT concept are aimed at designing new therapeutic approaches that interfere with the plasticity of carcinoma cells. Our laboratory has devised a high-content, high-throughput screen for EMT. Several combinations of drugs have been shown to selectively inhibit EMT. This strategy may be used to interfere with tumour progression, particularly in breast carcinomas that have acquired resistance to conventional therapies.

Aggressive Systemic Mastocytosis Is Associated with a High Kit D816V Allele Burden in Peripheral Blood.

Abstract 2899Poster Board II-875According to 2008 WHO definitions, diagnosis of systemic mastocytosis (SM) is based on the presence of one major criteria (multifocal dense infiltrates of mast cells in bone marrow or organ biopsies) and at least one of the following minor criteria (i) >25% are atypical cells on bone marrow smears or are spindle-shaped in mast cell infiltrates of visceral organs, ii) KIT point mutation at codon 816 in the bone marrow or other extracutaneous organs, iii) mast cells express CD2 and/or CD25, iv) baseline serum tryptase concentration >20 ng/mL) or the presence of at least three minor criteria. Patients with aggressive SM (ASM) have to present with one or more C-findings (i) neutrophils <1,000/μL, Hb <10g/dL, or platelets <100,000/μL, ii) hepatomegaly with impaired liver function – elevated transaminases and/or bilirubin levels and/or hypoalbuminemia, iii) palpable splenomegaly with signs of hypersplenism, iv) malabsorption with significant hypoalbuminemia and/or significant loss. ASM and MCL are clearly associated with an inferior survival. The activating KIT D816V point mutation is thought to be pivotal for pathogenesis and potential targeted therapy with novel tyrosine kinase inhibitors. However, conventional sequencing (CS) of RNA/DNA extracted from bone marrow (BM) samples of SM patients reveals the mutation in less than 50-60% of patients while peripheral blood (PB) samples are frequently negative as consequence of low numbers of malignant cells and poor assay sensitivity. For better qualitative and additional quantitative assessment of the KIT D816V allele burden (expressed as ratio KIT D816V vs. KIT wildtype), we sought to establish (i) a D-HPLC (denaturing-high performance liquid chromatography) assay combined with direct sequencing in case of a positive D-HPLC signal and (ii) a LightCyclerTM based quantitative PCR (RQ-PCR). The assay sensitivities were calculated through serial cell (KIT D816V positive HMC-1 cells in NB4 cells) and RNA dilutions. The detection limit was estimated between 0.1 and 0.5% for both assays which was thus significantly improved in comparison to the detection limit of CS which was at 10–15%. Patient material was available from BM (n=134) and PB (n=93) from 173 patients (88 m, 85 f, median age 54 years) with diagnosis of SM including 10 patients with confirmed ASM (n=9) or aleukemic variant of MCL (n=1) according to WHO definitions. At diagnosis, D-HPLC, RQ-PCR and CS were positive in 78% (104/134), 84% (112/134) and 60% (80/134) of BM samples, respectively. Two patients had a KIT D816H and one patient had a KIT D816L mutation. In 54 cases with contemporaneously collected BM and PB samples, the KIT D816V mutation was found in PB of BM positive patients by D-HPLC, RQ-PCR and CS in 47% (22/46), 55% (27/49) and 38% (14/37) of cases, respectively. This information allowed the detection of the KIT D816V mutation in an additional 27 of 39 (69%) patients without available bone marrow biopsies. All ASM patients were KIT D816V positive in PB with a median KIT D816V allele burden of 36% (range 26–98%) vs. 7.8% (range 0.1–61%) in other stages of SM (p=0.0021). Eleven of 124 (8.9%) SM patients with a KIT D816V allele burden >20% are currently explored for the potential diagnosis of ASM or MCL. In conclusion, D-HPLC is a reliable and sensitive method for the screening of variable KIT mutations in BM and PB of SM patients and is clearly superior to CS. Application of RQ-PCR assays for the most common D816V mutation may overlook rare mutations but allows quantification of the KIT D816V allele burden which may be useful for diagnosis of ASM and monitoring of residual disease during treatment with novel tyrosine kinase inhibitors, e.g. midostaurin or dasatinib. Disclosures:No relevant conflicts of interest to declare.

Genomic Profiles Associated with Early Micrometastasis in Lung Cancer: Relevance of 4q Deletion

Bone marrow is a common homing organ for early disseminated tumor cells (DTC) and their presence can predict the subsequent occurrence of overt metastasis and survival in lung cancer. It is still unclear whether the shedding of DTC from the primary tumor is a random process or a selective release driven by a specific genomic pattern. DTCs were identified in bone marrow from lung cancer patients by an immunocytochemical cytokeratin assay. Genomic aberrations and expression profiles of the respective primary tumors were assessed by microarrays and fluorescence in situ hybridization analyses. The most significant results were validated on an independent set of primary lung tumors and brain metastases. Combination of DNA copy number profiles (array comparative genomic hybridization) with gene expression profiles identified five chromosomal regions differentiating bone marrow-negative from bone marrow-positive patients (4q12-q32, 10p12-p11, 10q21-q22, 17q21, and 20q11-q13). Copy number changes of 4q12-q32 were the most prominent finding, containing the highest number of differentially expressed genes irrespective of chromosomal size (P=0.018). Fluorescence in situ hybridization analyses on further primary lung tumor samples confirmed the association between loss of 4q and bone marrow-positive status. In bone marrow-positive patients, 4q was frequently lost (37% versus 7%), whereas gains could be commonly found among bone marrow-negative patients (7% versus 17%). The same loss was also found to be common in brain metastases from both small and non-small cell lung cancer patients (39%). Thus, our data indicate, for the first time, that early hematogenous dissemination of tumor cells might be driven by a specific pattern of genomic changes.

Bone marrow cytokeratin 19 mRNA level is an independent predictor of relapse-free survival in operable breast cancer patients

To study the prognostic significance of elevated cytokeratin 19 (CK19) mRNA levels in the bone marrow (BM) of operable breast cancer patients. From 1998 to 2000, BM was collected from 195 consecutive breast cancer patients immediately prior to surgery and from 34 healthy volunteers. The patients received surgical and adjuvant treatment according to national guidelines at the time. We analyzed the level of CK19 mRNA in the BM samples from patients and normal controls using a real-time RT-PCR assay. The associations with known prognostic factors and the impact of pathological CK19 mRNA levels on patients' prognosis were investigated. Using the 99 percentile of the normal control group as a cut-off, 24 (12%) of the 195 patients and 1 (3%) of the 34 volunteers were diagnosed as CK19 mRNA positive. There was no correlation between CK19 BM status and the clinicopathological factors tested. During a median follow-up of 72 months, 7 (29%) of the 24 CK19 mRNA BM positive patients experienced systemic relapse compared to 20 (12%) of the 171 in the CK19 mRNA negative group. The patients with CK19 mRNA-positive BM had significantly shorter systemic recurrence-free survival (P=0.01) and overall recurrence-free survival (P=0.005). Multivariate Cox regression showed CK19 mRNA BM status to be an independent predictor of relapse. Detection of CK19 mRNA in the BM of breast cancer patients by real-time RT-PCR is an independent predictor of relapse-free survival in operable breast cancer patients.

Apoptotic disseminated tumor cells reflect response to primary chemotherapy in breast cancer

654 Background: Primary chemotherapy (pCHT) is an established method to reduce tumor size (downstaging) in breast cancer patients before performing breast conserving therapy. The consequences of pCHT on tumor cell dissemination in these patients are not known. The aim of this study was to investigate (1) the incidence of disseminated tumor cells (DTC) including apoptotic DTC in patients with breast cancer after primary chemotherapy and (2) its correlation with pathological therapy response. Methods: Bone marrow aspiration was performed in 157 patients after primary chemotherapy. Cytokeratin-positive cells were detected by immunocytochemistry using the AB45-B/B3 anti-cytokeratin antibody. For detection of apoptotic tumor cells the antibody M30 (Roche Diagnostics, Germany) was used. M30 reacts with a neo-epitope expressed only after caspase cleavage of CK 18 during early apoptosis. Results: The incidence of disseminated tumor cells in breast cancer patients was 57% (84 of 157 pts) after completion of primary systemic therapy. Tumor dissemination was observed more frequently in patients with no change/progressive disease (NC+PD: 63%) than in those who showed partial (PR) or complete remission (CR) of the primary tumor (PR+CR: 43%) (p&lt;0.05). However, 9 of 23 (40%) patients with complete response were still bone marrow positive. Apoptotic tumor cells were present in 36 of 157 (23%) breast cancer patients. The positivity rate of apoptotic cells was higher in bone marrow positive patients with PR or CR (42%) compared to those with stable disease (SD) (26%). No apoptotic tumor cells were detected in patients with tumor progression (n=5). Conclusions: The pathological therapy response is reflected by the presence of apoptotic tumor cells in the bone marrow of breast cancer patients. However, patients with complete response may still have non apoptotic disseminated tumor cells. Patients with tumor cell dissemination after primary systemic therapy may be benefit from additional secondary adjuvant treatment (e.g. bisphosphonates, antibody based strategies). No significant financial relationships to disclose.

Bone marrow micrometastases and adjuvant treatment of breast cancer.

The immunohistochemical detection of epithelially derived cells in the bone marrow of patients with primary breast cancer has been shown to be associated with increased risk of distant relapse as well as higher rates of cancer-related death. Despite the correlation between bone marrow micrometastases and poor outcome in breast cancer patients, bone marrow status does not yet have an established role in patient management. In this prospective study, adjuvant therapy recommendations for 43 patients with stage I, II, or III breast cancer treated with lumpectomy or mastectomy, sentinel lymph node biopsy and/or axillary dissection, and intraoperative bone marrow aspiration were recorded. Recommendations were made by a multidisciplinary tumor board both blinded and unblinded to the results of the bone marrow aspiration. In our study, 10 of the 43 breast cancer patients were found to have bone marrow micrometastases. Four of these patients (40%) had axillary lymph node metastases. When blinded to the results of the bone marrow aspiration, the tumor board recommended adjuvant chemotherapy for these four node-positive patients, as well as two node-negative patients. When unblinded to the results of the bone marrow aspiration, the tumor board did not change its recommendations for any of these six patients. The remaining four node-negative, bone marrow-positive patients were not advised to have adjuvant chemotherapy by the tumor board when blinded to bone marrow status. However, once the tumor board was informed of the presence of bone marrow micrometastases, adjuvant chemotherapy was recommended for all of these patients. The results of this pilot study indicate that the presence of bone marrow micrometastases in breast cancer patients with stage I, II, or III disease does influence recommendations for adjuvant chemotherapy, particularly in patients with node-negative disease.

Bone-marrow microinvolvement in non-small cell lung cancer is not a reliable indicator of tumour recurrence and prognosis

Aims: This study aimed to examine the incidence of bone-marrow microinvolvement in non-small cell lung cancer (NSCLC) patients and its correlation with tumour recurrence and prognosis. Methods: Between March 1997 and August 1998, we analysed 96 bone-marrow specimens (from the posterior iliac crest) of NSCLC patients before surgery. Tumour differentiation showed well differentiated carcinoma in six, moderately differentiated carcinoma in 69, and poorly differentiated carcinoma in 21. p-TNM staging showed stage Ia in five, stage Ib in 33, stage IIb in 19, stage IIIa in 26, stage IIIb in eight, and stage IV in five. The specimens were examined by immunohistochemical staining with anti-human cytokeratin AE1/AE3 and clone MNF116 mixed solution (Ab1, n=96) and/or Ber-EP4 (Ab2, n=80) to detect the presence of malignant epithelial cells in the bone marrow. Results: Positive results were observed in 21 patients (21.9%). The occurrence of bone-marrow microinvolvement was not related to patient age, sex, cell type, or TNM status. The 30-month disease-free survival rates were 50.2% and 53.9% in bone-marrow negative and bone-marrow positive patients, respectively (P=0.5670); the 30-month cumulative survival rates were 66.7% and 67.6% in bone-marrow negative and bone-marrow positive patients, respectively (P=0.9351). Multivariate analysis failed to demonstrate bone-marrow microinvolvement as an independent prognostic factor. Conclusions: Our results show that bone-marrow microinvolvement is not unusual, and its occurrence cannot be translated into early tumour recurrence or poor outcome during an intermediate-term follow-up, which means bone-marrow microinvolvement may be an epiphenomenon rather than true metastasis in NSCLC.

Immunocytochemical detection of tumor cells in bone marrow as a prognostic factor in breast carcinoma

In a prospective study at the University of Erlangen, Dept. Gynaecol, and Obstet., 228 patients with breast cancer during their primary surgery and 20 patients during their metastatic surgery, underwent bone marrow punctions at six punction sides, which were twice at the sternum and twice at both iliac crest. The control group was 20 patients without an invasive carcinoma. Aim of the study was to detect or exclude tumour cells in the bone marrow via examination of the biopsies with monoclonal antibodies EMA and cytokeratin and consequently to find out the meaning of the results as prognostic criteria by statistical measurements. Tumour cells in the bone marrow were detected in 46.5% (106/228) of the patients, who underwent a bone marrow biopsy during primary surgery. 21% (23/106) of the patients who were bone marrow positive, but only 5.75% (7/122) of the patients, who were bone marrow negative, developed metastases during a median follow-up of 20 months. This difference is statistically significant. 17 of the 30 patients with recurrences developed bone metastases; 16 of them were EMA-positive. The median recurrence-free interval was 5 months in the bone marrow positive group and therefore noticeably shorter, than in the bone marrow negative patient group with 11 months. Of the nodal negative patients, 2 bone marrow positive patients developed distant metastases. With the knowledge of the nodal status and bone marrow biopsy result, it was possible to predict 28 of the 30 patients correctly in respect of their risk to metastasize. The result of the bone marrow puncture was proved in a multivariate analysis to be an independent prognostic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone marrow examination in small cell lung cancer--when is it indicated?

To assess the usefulness of bone marrow (BM) examination performed as part of the staging procedure in SCLC, 137 patients with this neoplasm were studied. At diagnosis, BM was infiltrated in 23 patients (17%) and in 5 of them (22%) it was the only metastatic site. BM examination changed the previously given stage in 9% of the patients who were supposed to have limited disease before this test was performed. BM involvement correlated with a higher frequency of bone (p less than 0.05) and liver (p less than 0.01) metastasis. Correlations were found neither with blood or serum biochemistry disturbances nor with postchemotherapy haematologic toxicity. The BM positive patients had a survival rate similar to those with extensive disease but without BM infiltration. We conclude that BM examination should be performed only when no other metastatic sites have been found after a complete staging study.

Lymphoblastic lymphoma in adults: a study on 30 patients treated with two different programs according to bone marrow findings.

Thirty adult patients with lymphoblastic lymphoma were treated with two different programs according to bone marrow findings. Bone marrow positive patients were given an ALL-like program: vincristine, daunorubicin, cyclophosphamide and prednisone for induction of remission, CNS prophylaxis, continuous maintenance for three years and monthly reinductions. Bone marrow negative patients were given a conventional lymphoma program with CHOP-Bleo and limited RT on bulky mediastinum without CNS prophylaxis. The CR rate of the whole group was 54% (62% for ALL-treated versus 47% for lymphoma-treated patients; not significantly different), with a median survival for remitters of 28.5 mos. Relapse-free survival of the whole group was 65% at 12 and 25% at 24 mos. Stage IV ALL-treated patients had a median survival of 16.5 versus 10 mos for stage IV lymphoma-treated ones (p = 0.05); the three-years survival was 24 and 10%, respectively. No patients undergoing CNS prophylaxis (ALL-therapy) had neurological complications or late meningeal relapse. The better prognosis of ALL-treated patients, in spite of bone marrow positivity, argues in favor of an ALL-like therapy in all adult lymphoblastic lymphomas, in terms of CR rate, overall survival, and absence of CNS relapse. This therapy must be adopted irrespective of bone marrow findings, and regardless of how localized the lymphoma appears to be.