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Expression of thioredoxin-1 (TXN) and CXCL9 is not restricted to THRLBCL macrophages, but may be observed in histiocytes and neoplastic (HRS) cells of EBV + mixed cellularity (MC) classical Hodgkin lymphoma (cHL) and nodular lymphocyte predominant HL. We aimed to validate and extend the above observations in 174 cHL patients evaluating the immunohistochemical expression of TXN, CXCL9 and IFN-γ. HRS-cell CXCL9 expression was higher in latent membrane protein-1 (LMP1)+, MC and Stage IV. TXN and CXCL9 expression by cHL histiocytes was more frequent in LMP1+, MC and older patients (only for CXCL9). TXN expression by HRS cells (≥80%) was independently associated with better failure-free survival. In conclusion, markers of TCHRLBCL histiocytes (TXN, CXCL9), as well as IFN-γ are also expressed by histiocyte subsets and neoplastic cells of cHL. The expression of some of them is more prominent in EBV + MC, but not restricted to this subtype. The prognostic implication of TXN needs further evaluation.

Extramedullary plasmacytomas constitute a rare and not well studied subset of multiple myeloma (MM) relapses. We report the incidence, clinical-laboratory features and outcome of patients with MM and extramedullary relapse (ExMeR). A total of 303 patients with symptomatic MM were recorded in a 13-year period in two institutions. Twenty-eight cases of ExMeR (9%) were recorded. There was an increased frequency of elevated lactate dehydrogenase (LDH) (p = 0.026), bone plasmacytomas (p = 0.001) and fractures (p = 0.002) at diagnosis, in patients with ExMeR compared to the others. ExMeR was associated with an ominous outcome, high LDH, constitutional symptoms and a statistically significant decrease of monoclonal paraprotein compared to levels at diagnosis (p = 0.009). Prior treatment with bortezomib was associated with a decreased hazard of ExMeR (p = 0.041). Overall survival (OS) was decreased in patients with ExMeR compared to the others (38 vs. 59 months, p = 0.006). Patients with MM with ExMeR have a lower OS and their clinical and laboratory features differ from those without.

Spontaneous remission of acute myeloid leukemia (AML) in adults is a rare but well documented phenomenon. This study reports on a 64-year-old male patient with acute myelogenous leukemia (AML-M4, according to the French-American-British classification) that was developed on a background of chronic myelomonocytic leukemia (CMML) and then underwent remission after treatment with the gonadotropin-releasing hormone agonist (GnRH agonist) triptorelin for presumed prostate cancer. Remission persisted for at least 4 years before the patient was lost to follow-up. To the author' knowledge, this is the first report of remission in an AML-M4 case associated with hormone manipulation. Possible mechanisms of this phenomenon are discussed.

Several studies have indicated that age, hemoglobin and serum albumin are among the most important prognostic factors for survival of patients with Waldenstrom's macroglobulinemia (WM). Furthermore, recent data indicate that serum b2-microglobulin may be also significant. The recently proposed International Staging System (ISS) for multiple myeloma is based on serum albumin and b2-microglobulin. We designed a study to assess this model in patients with WM. Our analysis included 83 previously untreated patients with WM who required systemic treatment and in whom pretreatment values for both serum albumin and b2-microglobulin were available. Based on these variables the patients were stratified into three ISS stages. Stage I: albumin > or = 3.5 g/dl and b2-microglobulin < 3.5 mg/dl, stage II: albumin < 3.5 g/dl and b2-microglobulin < 3.5 mg/gl or b2-microglobulin 3.5-5.5 mg/dl and stage III: b2-microglobulin > 5.5 mg/dl. Low albumin (< 3.5 g/dl) and high b2-microglobulin (> or = 3.5 mg/dl) were recorded in 45% and 52% of patients respectively. The distribution of patients in the three ISS stages was: stage I: 30%, stage II: 43% and stage III: 27%. The median overall survival from the date of treatment initiation was 115 months. The median survival according to ISS was not reached for stage I, 116 months for stage II and 54 months for stage III (P = 0.02). Our analysis indicated that the recently proposed ISS for multiple myeloma could stratify the patients with WM into three distinct subgroups with significantly different survival times. If this model is validated in independent series, it could provide a new staging system for WM based on readily available and reproducible variables., (Copyright 2004 Taylor and Francis Ltd)

We evaluated immunohistochemically the expression of two negative regulators of the cell cycle, namely retinoblastoma gene product (pRb) and WAF1/Cip1 gene product (p21), in paraffin sections from 93 patients with non-Hodgkin's lymphomas (NHL) and related it to clinicopathological parameters, proliferative fraction, p53 expression and survival. Patients were followed until death (n=33) or for an average of 52 months (60-160). Rb labelling index (LI) increased with malignancy grade and proliferative activity but was unrelated to other clinicopathological parameters. In 33% of cases, especially those of the aggressive groups, we observed diminished pRb expression (i.e. low pRb/Ki-67 ratio). p21 expression on the other hand correlated only with histological grade, Rb LI and p53 LI. In multivariate analysis, Rb LI was a negative predictor of disease-free survival but was linked to a higher probability of complete response. However, diminished pRb expression as well as p21 expression were not statistically significant prognostic indicators. Our results suggest that pRb as a cell cycle related molecule may play an important role in determining prognosis and therapeutic response in NHL patients.

Thirty three B-chronic lymphoproliferative disorder (B-CLD) patients [22 with B-chronic lymphocytic leukemia (B-CLL), 5 with small lymphocytic lymphoma (SLL) and 6 with lymphoplasmacytic lymphoma (LPL)] with anaemia (Ht <32%) of no other cause but their disease, received recombinant human erythropoietin (r-HuEPO). The treatment protocol provided r-HuEPO in a dose of 150 U/kg s.c. thrice weekly for 3 mo. After 1.5 mo of r-HuEPO administration, if response was not satisfactory, r-HuEPO dose escalation was utilised by giving incremental doses of 50 U/kg more than the previous dose up to a maximum dose of 300 U/kg tiw. After maximal response, half of the responding patients discontinued therapy, while the other half received maintenance therapy at a dose of 150 U/kg s.c./w. Oral iron was given throughout the study. Pretreatment EPO levels were determined in all patients. A complete response (CR) was defined when Ht was >38% and a partial response (PR) when there was an increase of the Ht >6% from the initial value was achieved. Sixteen of the 22 B-CLL patients had Rai stage III disease and 6 stage IV, with a median duration of anaemia 27 months (6-38); twelve of them were receiving chlorambucil while the rest were on no treatment. Of the SLL and LPL group, 4 patients had Ann Arbor stage III disease and 7 stage IV with a median duration of anaemia 24 months (5-36); 8 patients were on chlorambucil. Complete response was achieved in 50% of the B-CLL group and 54% of the SLL and LPL group, with an overall response rate of 77% and 81% respectively. All patients on maintenance therapy had a continuous response, while all patients, in whom rHuEPO was discontinued, relapsed. No correlation was found between patients: with low or high pretreatment serum EPO levels; those receiving concomitant therapy or not; those with B-symptoms or not; those with a non-diffuse or diffuse bone marrow infiltration pattern; and with splenomegaly or not. Life quality was significantly improved and no major side effects were encountered. We conclude from our study that r-HuEPO is very effective in correcting disease-related anaemia in B-CLD, resulting in down-staging of Rai stage III patients and that maintenance therapy is necessary. Whether the correction of anaemia improves patients' overall survival, still remains to be seen.

Primary non-Hodgkin lymphoma of the gallbladder is a very rare location of extranodal non-Hodgkin lymphomas. A patient with a primary non-Hodgkin lymphoma of the gallbladder is reported and in addition, the English literature is reviewed. Clinical presentation, diagnostic evaluation, histopathologic findings, treatment modalities and prognosis of primary gallbladder lymphomas reported up to date are reviewed and discussed. Our patient was diagnosed as a T-cell lymphoblastic lymphoma, after cholecystectomy, and had no evidence of disease elsewhere. She was treated with combination chemotherapy and complete remission was achieved. She remains free of disease 9 years later. Review of the literature over a 30-year period revealed only 12 cases of well-documented primary non-Hodgkin lymphoma involvement of the gallbladder, including the present case. Patients present clinically with symptoms and signs indicating either biliary tract pathology or a gastrointestinal tumor. Diagnostic investigation included ultrasound of the upper abdomen, computed tomography of the abdomen and pelvis, oral cholecystography, percutaneous cholangiography and endoscopic retrograde cholangiopangreatography. Preoperative diagnosis was established in none of the patients. Treatment modalities included surgery and postoperative chemotherapy and irradiation. The prognosis is overall poor and only 2 patients are alive after 1 and 9 years respectively, the latter being our case. Here we document the first reported case of a patient with primary T-cell lymphoblastic non-Hodgkin lymphoma of the gallbladder. Review of the literature shows the existence of non-Hodgkin lymphoma of the gallbladder, its rarity and its general dismal prognosis.

To evaluate the efficacy of EBVD combination chemotherapy followed by low dose (LD) involved field (IF) radiation therapy (RT) in patients with clinical stage (CS) I-IIA Hodgkin's disease (HD), we analyzed 148 patients treated in our Unit from March 1988 to November 1995. EBVD consisted of Epirubicine 40 mg/m2, Bleomycin 10 mg/m2, Vinblastine 6 mg/m2 and Dacarbazine 300 mg. All drugs were administered i.v. at days 1 and 15, every 4 weeks, for a total of 4-6 cycles. LDIF RT (24-32 Gy) was scheduled for patients with complete response (CR) or >90% reduction of tumor load, after EBVD. Patients with stable or progressive disease (SD, PD) after EBVDx3 or poor compliance to the regimen received mantle or inverted Y RT at standard dose. The median follow-up of patients currently alive was 71.5 months. 129 patients achieved a CR after EBVD and 10 a >90% reduction of tumor load, for a post-CT response rate of 94%. Eight patients had SD after EBVDx3 and one had a partial response with poor compliance. All 9 patients received mantle or inverted Y RT and 8/9 achieved a CR. Nine patients relapsed at a median of 7 months from the end of treatment. At 10 years, FFS was 90% and overall survival 95%. Six patients have died so far; 5 of HD and one of stroke. One patient developed a diffuse large cell lymphoma 48 months after the diagnosis of HD. We conclude that EBVD followed by LDIF RT is a highly effective regimen for patients with CS I-IIA HD. Longer follow up is required to assess the risk of secondary malignancies, especially solid tumors.

We investigated the prognostic value of proliferating cell nuclear antigen (PCNA) and p53 oncoprotein expression and of nucleolar organiser region (NOR) scoring, in relation to classic clinicopathological parameters, in a series of non-Hodgkin's lymphomas (NHL). Paraffin embedded tissue from 91 patients with NHL was stained immunohistochemically with the monoclonal antibodies PC-10 (PCNA) and DO-1 (p53) and histochemically with the AgNOR technique. The median follow-up was 48 (4 to 193) months. The impact of PCNA and p53 expression and of AgNOR number on survival was tested using univariate as well as multivariate analysis, in order to circumvent the heterogeneity in histologic grade, type and therapy. Univariate analysis identified seven variables related to overall survival: histologic type and grade, clinical stage, chemotherapy, p53 labelling index (LI), PCNA LI and AgNOR score, whereas only one parameter i.e. histologic grade influenced disease-free survival. In multivariate analysis stage, PCNA LI and AgNOR score predicted independently overall survival. PCNA was also the only independent predictor of post-relapse survival and histologic grade the most important indicator of disease-free survival. In conclusion, PCNA expression and AgNOR number may be better predictors of overall and post-relapse survival than histologic grade. The latter remains the most valuable prognostic indicator of disease-free survival.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder characterised by an unusual sensitivity of abnormal red cell population(s) to complement lysis, due to a complete or incomplete defect of various surface molecules, including CD55 and CD59. PNH has been associated with various hematological disorders. Using a newly introduced method, the Sephacryl gel test microtyping system, we investigated the presence of CD55 or CD59 defective red cell populations in several hematological disorders. It was also found that a large proportion of such patients possess CD55 deficient populations, while a smaller but still significant proportion possess CD59 deficient populations. Defective red cell populations were detected in normal subjects as well. These findings need further investigation. Nevertheless the Sephacryl Gel Test microtyping system although non specific, seems to be useful in screening for the PNH and/or "PNH-like" red cell defect in several hematological disorders.

In the present study we report our results on the efficacy of Fludarabine monophosphate in 20 B-chronic lymphocytic leukemia (CLL) patients, refractory to conventional chemotherapy. Of the 20 patients 14 were males and 6 females with a median age of 58 years (44-70). Eight had Binet stage B and 12 stage C. They were previously treated with chlorambucil, prednisone, mini-CHOP or irradiation. Their disease duration prior to fludarabine administration was 49 months (7-180). Fludarabine was given at a dose of 25 mg/m2 daily, for five consecutive days, monthly for six months and if responding for six additional months. Treatment was administered on an outpatient basis. Complete response (CR) was observed in 7 patients (33%) and partial remission (PR) in 5 (25%). Of the complete responders 5 were males and 2 females with a median age of 60 years (range 55-68); three of them had stage B and 4 stage C disease; the median number of fludarabine courses for achieving CR was 3 (range 2-5). In all CR patients a residual monoclonal CD5/CD19 positive lymphocyte population was found in the peripheral blood. All CRs relapsed shortly after discontinuation of therapy within 12 months. The main toxicity observed was upper respiratory tract and/or pulmonary infections in 8 patients, requiring hospitalization. Among the CRs one patient died during the administration of the third course of therapy, due to a severe hypersensitivity reaction with Stevens-Johnson syndrome. The importance of maintenance therapy is also stressed as PR was sustained in some patients using 3 day cycles every 2-4 months. One patient was maintained in this fashion for 60 + months. This study showed that fludarabine is effective in CLL patients refractory to conventional chemotherapy thus it may be given as the treatment of choice if such patients still require treatment.

The breakpoints on chromosome 22 in CML occur within a 5.8 kb region called the Major breakpoint cluster region (M-bcr). DNA mapping within the M-bcr region was performed in 41 long term followed Ph1-positive CML patients using the Southern blot technique. The purpose of this study was to determine whether localization of M-bcr breakpoint correlates with the length of chronic phase of the disease, blastic crisis lineage and thrombocytosis at the time of initial diagnosis. Our results fail to indicate any correlation between breakpoint localization and duration of chronic phase, blastic crisis lineage and platelet count at diagnosis.

The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukaemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) and alpha-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukaemia.

Large multilobated cell lymphomas represent an heterogenous group comprising both B-cell and T-cell subtypes. The correct lineage identification of each subtype cannot be based on morphologic grounds, as it has already been stressed by other authors, and demands the use of immunophenotyping methods. In this study we review the literature and present eight new cases of large multilobated B-cell lymphoma which have been immunophenotyped in paraffin sections with a panel of monoclonal [L26 (CD20), 4KB5 (CD45R), UCHL1 (CD45RO), MT1 (CD43)] and polyclonal (anti-CD3, anti-kappa, anti-lambda) antibodies. We further investigated the expression of c-myc p62 oncoprotein and of proliferating cell nuclear antigen (PCNA) using the monoclonal antibodies c-myc 1-9E10 and PC-10 respectively. In all cases the neoplastic cells were positive for L26 (CD20) and negative for anti-CD3. Five cases were positive for 4KB5 (CD45R) while six cases stained positively for UCHL1 (CD45RO) or MT1 (CD43). Four cases were monoclonal in respect to light chain restriction. Immunoreactivity with c-myc 1-9E10 and PC-10 was observed in all cases. As far as c-myc 1-9E10 is concerned, positive cells constituted more than 45% of the neoplastic population in six cases, whereas in all cases the percentage of PC-10 positive cells was greater than 45%. The staining pattern was nuclear and/or cytoplasmic for c-myc 1-9E10 but solely nuclear for PC-10. The elevated c-myc and PCNA expression are indices of high proliferation rate in this type of lymphoma and may suggest a high malignancy grade.

Salvage treatment modalities for refractory low grade non-Hodgkin's lymphomas (LGNHL) are limited. In the present analysis we investigate the effectiveness of mitoxanthrone monotherapy in resistant LGNHL. Fourteen patients from our Unit were studied. Eligibility criteria were as follows: histologic type of LGNHL, performance status 0, 1 or 2, clinical stage II, III or IV, A or B and refractoriness to conventional chemotherapy. The treatment protocol provided intravenous infusion of mitoxanthrone 6 mg/m2 daily for 3 days every three to four weeks. The median number of treatment cycles until now was 4 (1-8). A minimum of 3 cycles was necessary for documentation of response. For the staging and response of our patients well known criteria were used. The term minor response (MR) was introduced for those patients who had less than 50% disease regression. Of the 14 patients one could not be evaluated. Among the remaining 13, one achieved complete remission (CR) (7.7%), six partial remissions (PR) (46.2%), three MR (23%), two remained stable (SD) (15.4%) and one had disease progression (DP) (7.7%). Overall response rate (CR + PR) was 53.9%. Response to treatment was better in patients with less pretreatment (one-two prior treatments) than in heavily pretreated ones (more than three) and this relation was found to be statistically significant (p < 0.05). In addition it seems that follicular small cleaved or mixed lymphoma and patients with less bulky disease responded better, although these differences could not be documented as statistically significant. The follow up of our patients is too short for any meaningful conclusions about the duration of response to be drawn.(ABSTRACT TRUNCATED AT 250 WORDS)

The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) and alpha-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukemia.

Sera from 60 patients with non-Hodgkin's lymphomas (NHL) were tested by isoelectric focusing (IEF) and immunoblotting (IB) techniques for the presence of monoclonal or oligoclonal immunoglobulins (Ig). Of the 60 NHL patients, 18 were newly diagnosed and had not received any treatment while the rest had received some chemotherapy in the past. Two serum samples were obtained from 27 patients over the treatment period. Oligoclonal Ig patterns were detected in 34 of the 60 (56.6%) sera, and were further identified by IB as IgG of mixed kappa (K) and lambda (λ) types. Seven of the 18 (38.8%) newly diagnosed NHL patients had these oligoclonal bands, compared with 27 of the 42 (69%) who had received chemotherapy in the past. In 11 of these 27 (40.7%) patients, follow-up studies revealed the appearance of new Ig bands (9 cases) with the disappearance of preexisting ones (2 cases). After treatment of sera with 2-mercaptoethanol, monoclonal IgM was detected in 39 of the 60 (65%) NHL patients. These monoclonal Ig spikes occurred together with oligoclonal IgG (20/60 cases) or appeared in the absence of oligoclonal IgG (19/60 cases), while oligoclonal IgG could also appear as the sole serum finding (14/60 cases). There was a higher prevalence of monoclonal IgM among patients with stage IV disease and of oligoclonal IgG among patients with high grade of malignancy NHL. Our results demonstrate that among patients with NHL there is a high prevalence of monoclonal or oligoclonal Ig bands detected by highly sensitive methods such as IEF and IB.

In the present study we investigated whether prolonged intermittent chlorambucil (Chl) administration is more effective for B-chronic lymphocytic leukemia (B-CLL) patients, compared to the traditional mode of shorter duration. One hundred and seventeen patients, entered the study, were scheduled to receive Chl orally for 10 days/mo, in a dose of 10 mg/daily, for a maximum period of 24 mo. Eighty-one patients (54M/27F), who had completed at least 10 mo of therapy were analyzed. Their median age was 60 yrs (30-80). Nine patients were stage A, 27 stage B and 45 stage C. Their median follow-up time from initiation of treatment was 40 mo (12-108). They received Chl for a median period of 18 mo (12-24). The overall response rate of our patients at six and 18 mo was similar (approximately 90%). However, there was a significant increase of complete responders at 18 mo compared to those at six mo of therapy (14/67 or 21% and 6/81 or 7.4%, respectively) (p < 0.025). Overall survival from the initiation of therapy according to the stage was as follows: stage A 50 mo, stage B 51 mo and stage C 33 mo. No statistically significant differences in survival among the three stages was found. No toxicity or increased incidence of second malignancy was observed except for one patient who was extremely sensitive to Chl and in whom therapy had to be discontinued temporarily. We concluded that at 18 mo of Chl administration the highest response had been achieved and that overall survival of stage C patients was similar to that at stages A and B.

We describe six rare patients with B-type CLL under the age of 30 years. All were males and four showed a relatively aggressive clinical course requiring initial chemotherapy at an early stage of their disease. Four of the six patients developed prominent generalized lymphadenopathy accompanied by splenomegaly and a rapid increase in the peripheral blood lymphocyte count or a doubling time of less than 12 months and were symptomatic. Of the six cases, one still has Stage A (0) disease, 16 months after diagnosis and has not yet been treated, while another 29 year old male, initially stage C (3) at diagnosis, progressed rapidly, despite chemotherapy and died after 42 months. Of the remaining four patients all responded well to treatment initially, however one 24 year old male has progressed rapidly from stage A (2) to Stage B (2), 14 months after initial response to chlorambucil and prednisone. Two patients remain in Stage A (0), two and eight years respectively after chemotherapy; while the patient with the longest follow up is currently 39 years old in good partial remission with Stage A (0) disease ten years after initial diagnosis, having responded well to Fludarabine, following a major flare up of his disease recently. The rare phenomenon of young patients with CLL is reviewed and management options relating to new therapeutic approaches for this sub-population of young patients are discussed.

Whether all younger adult patients with chronic lymphocytic leukemia (CLL) should be offered intensive and/or experimental treatments is currently undecided. In order to investigate the natural history and prognosis of CLL in younger adults, information on 454 B-CLL patients less than 50 yrs old, from 13 different International groups was collected and analyzed. The male/female proportion is 1.46 (270/184) and the median age is 46 yrs (range, 20-49). Number of cases increases with age: nine patients (2%) are <30 yrs; 70 (14%) are 30 to 40 yrs; and 375 (84%) are 41 to 49 yrs. Clinical stages distribution is as follows: Rai O, 113 (25%), Rai I, 98 (21.5%), Rai II, 182 (40%), Rai III, 25 (5.5%), and Rai IV, 36 (8%); Binet's A, 235 (52%), Binet's B, 160 (35%), Binet's C 59 (13%). Bone marrow biopsy was available in 251 cases, being nodular in 46 (18.5%), interstitial in 76 (30%), mixed in 60 (24%), and diffuse in 69 (27.5%). Clinical characteristics of these patients do not differ from those described for entire series of CLL patients including all ages. The majority of patients (93%) were diagnosed between 1975 and 1989 and at the time of this analysis 138 (30.3%) have died. Infection accounts for the large majority of deaths (48%). Overall median survival is 12 yrs. Survival probability (±SD) is 73.55 ± 2.47% at 5 yrs, 51.04 ± 3.46% at 10 yrs, and 45.53 ± 4.08% at 15 yrs. Prognostic parameter identified in whole series of patients with CLL are also useful when applied to this special subset. Thus, patients in stage A, B, and C have, at 10 yrs after diagnosis, survival probabilities of 72.4%, 33.7%, and 21.2%, respectively. Rai stages also discriminate different risk-groups with a survival probability at 10 yrs of 76% for patients in stage 0, 45% for those in stage I + II, and 24% for patient in Stage III + IV. Patients with non-diffuse bone marrow pattern have a survival probability of 76% at 10 yrs compared to 28% for those with a diffuse pattern. Further analysis will refine both the prognostic assessment and the optimal treatment approach for these patients.

The expression of c-myc oncogene in neoplastic and non-neoplastic lymphoid tissue was studied using the specific monoclonal antibody myc 1-9E10 and the 3 step streptavidin-biotin immunoperoxidase method in paraffin sections. Twelve samples of non-neoplastic reactive lymph nodes of various etiology, 181 of non-Hodgkin's lymphomas (NHL), and five of hairy cell leukemia (HCL) were studied. The staining pattern was mainly nuclear but cytoplasmic reactions were also occasionally observed. The percentage of positive cells per total, cell population was estimated and all cases were classified into four groups: 0.-15%, 16-.30%, 31-45% and more than 45% positive cells. In the reactive lymph nodes, mainly germinal center cells were stained, but the percentage in eleven of the 12 cases was less than 15%. All cases of HCL were negative. In NHL lymphoma, only malignant cells were evaluated. Fifty-six per cent of cases of NHL had more than 15% positive cells. The percentage of positive cells was greater in high grade than in intermediate and low grade NHL (80.6x, 47.6%, and 10.6 respectively had more than 30:< positive cells). This correlation proved to be statistically significant (p < 0.001). The above findings suggest a relation between the expression of the c-myc oncogene and lymphomagenesis and indicate that (evaluation of the expression of c-myc in NHL may be helpful in determining the grade of malignancy.

A new biological parameter (ψ) has been obtained and proposed here to serve in the assessment of acute myeloid leukemia (AML) progression. It is a function of the activity of RNase H (EC 3.1.4.34), the latter determined in mononuclear cells from the peripheral blood of AML patients. Using a series of patients at the time of diagnosis and after 1-2 cycles of chemotherapy, the enzyme was assayed before the several times during chemotherapy. The derivation of 4 was based on evidence suggesting that the enzyme level correlates with the proliferating leukaemic blasts and their progenitors. Values ψ>1 signify the presence of clonogenic leukaemic progenitor cells in the peripheral circulation. When these high (> 1) ψ values were found during chemotherapy, in these cases it was possible to predict an increase of the peripheral blast pool, with 82% success, occurring 5-35 days before cytologic relapse. In the patients in whom at some stage during treatment, ψ acquired values above unity or in whom ψ increased progressively, survival time was in linear correlation with the time period from the initiation of treatment to the documentation of this high ψ estimate. These results suggest that a patient's relapse risk can be defined by ψ with some degree of precision.