Differences among young adults, adults and elderly chronic myeloid leukemia patients.

BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). CONCLUSIONS: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome. CLINICAL TRIAL NUMBERS: NCT00510926, NCT00514488, NCT00769327, NCT00481052.

Treatment discontinuation following low-dose TKIs in 248 chronic myeloid leukemia patients: Updated results from a campus CML real-life study.

TKIs long-term treatment in CML may lead to persistent adverse events (AEs) that can promote relevant morbidity and mortality. Consequently, TKIs dose reduction is often used to prevent AEs. However, data on its impact on successful treatment-free remission (TFR) are quite scarce. We conducted a retrospective study on the outcome of CML subjects who discontinued low-dose TKIs from 54 Italian hematology centers participating in the Campus CML network. Overall, 1.785 of 5.108 (35.0%) regularly followed CML patients were treated with low-dose TKIs, more frequently due to relevant comorbidities or AEs (1.288, 72.2%). TFR was attempted in 248 (13.9%) subjects, all but three while in deep molecular response (DMR). After a median follow-up of 24.9 months, 172 (69.4%) patients were still in TFR. TFR outcome was not influenced by gender, Sokal/ELTS risk scores, prior interferon, number and last type of TKI used prior to treatment cessation, DMR degree, reason for dose reduction or median TKIs duration. Conversely, TFR probability was significantly better in the absence of resistance to any prior TKI. In addition, patients with a longer DMR duration before TKI discontinuation (i.e., >6.8 years) and those with an e14a2 BCR::ABL1 transcript type showed a trend towards prolonged TFR. It should also be emphasized that only 30.6% of our cases suffered from molecular relapse, less than reported during full-dose TKI treatment. The use of low-dose TKIs does not appear to affect the likelihood of achieving a DMR and thus trying a treatment withdrawal, but might even promote the TFR rate.

Antigenic phenotype of myelomonocytic progenitors (CFU-GM) in chronic myeloproliferative disorders.

The antigenic phenotype of myelomonocytic progenitors [colony-forming unit granulocyte-macrophage (CFU-GM)] from 33 patients with chronic myeloproliferative disorders was investigated using four cytotoxic monoclonal antibodies. Monoclonal antibodies S3-13, S8-6, and S16-144 which recognize normal hemopoietic progenitors of different lineages reacted with almost all CFU-GM. R1B-19 monoclonal antibody identified two subpopulations of myelomonocytic progenitors (type 1 and 2 CFU-GM), as reported previously in normal subjects. In 3 of 11 patients with chronic myelogenous leukemia, in 1 of 2 patients with chronic myelomonocytic leukemia, and in 2 of 4 patients with polycythemia vera, a higher proportion of the more immature CFU-GM (type 1) was detected in bone marrow cells. The more differentiated CFU-GM (type 2) is not detectable in normal peripheral blood. By contrast, in 14 of 15 chronic myelogenous leukemia patients, in 1 of 2 chronic myelomonocytic leukemia patients and in 3 of 8 patients with idiopathic myelofibrosis, it was present in high to very high proportions. It is clear from these findings that the antigens present on normal CFU-GM are expressed in chronic myeloproliferative disorders. The proportion and distribution of type 1 and 2 CFU-GM, on the other hand, are very different from those observed in the normal subjects.

Trophoblast cell line conditioned medium for in vitro culture and antigenic characterization of acute myeloid leukemia clonogenic cells.

The colony-stimulating factor-containing supernatant of the human trophoblast cell line TPA-30-1 was used to stimulate in vitro growth of acute myeloid leukemia clonogenic cells from 54 patients. Prevalent colony growth (10-greater than 1000) was observed in 63% of cases. In 31% clusters and a few colonies (1-9/1 x 10(5) plated cells) were scored. Neither colonies nor clusters could be detected in the remaining 6%. The best growth was observed in subtype M5 (8 of 9 cases, 89%). Morphological examination and recloning tests suggested that the colonies originated from leukemic progenitors. TPA-30-1 supernatant stimulation can therefore be compared with that of phytohemagglutinin or phytohemagglutinin-leukocyte-conditioned medium. In addition it does not require T-lymphocyte removal and batch screening. Extension of the culture for antigenic characterization of acute myeloid leukemia clonogenic cells to more patients than in a previous study confirmed the existence of a subgroup (39%) of patients whose acute myeloid leukemia clonogenic cells constantly expressed late myeloid differentiation antigens recognized by the monoclonal antibody S4-7. Since S4-7 spares early normal hemopoietic progenitors, this subgroup (54% M2) can be considered as candidates for autologous bone marrow transplantation after in vitro purging with S4-7 monoclonal antibody and complement.

Self-renewal inhibition of acute myeloid leukemia clonogenic cells by biological inducers of differentiation.

We analyzed the maintenance of acute myeloid leukemia clonogenic cells (AML CFU-L) in liquid culture in the presence of five potential differentiation inducers: trans-retinoic acid, 1,25-dihydroxy vitamin D3, interferon gamma, granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), used singly and with two combined. The culture medium contained either fetal bovine or human serum from normal donors. CFU-L recovery after 7 days was compared to that observed in control cultures. Of AML cases and HL60 cells, 11/15 displayed greater than 50% CFU-L reduction in response to one or more inducers. In 8/9 responsive cases that underwent the nitroblue tetrazolium (NBT) reduction test, an increase in the percentage of functionally mature (NBT-positive) cells was detected. The combination of retinoic acid with interferon gamma was most effective in reducing CFU-L recovering (8 responsive/15 AML cases), G-CSF and M-CSF displayed either inhibitory or stimulatory activity in different AML cases. The type of serum employed generally did not affect the response to inducers of differentiation. No significant inhibition of the recovery of granulocyte-macrophage colony-forming units was determined by the five inducers in experiments with three normal bone marrow samples. Our experiments indicate that biological differentiation inducers can reduce AML CFU-L self-renewal and increase the proportion of differentiated cells at concentrations that do not affect normal myelopoiesis and could be achieved during treatments in vivo.

Human recombinant stem cell factor stimulates in vitro proliferation of acute myeloid leukemia cells and expands the clonogenic cell pool.

Stem cell factor (SCF) is a new growth factor acting on early hematopoietic progenitor and stem cells. In our experiments human recombinant SCF stimulated short-term proliferation of accessory cell-depleted acute myeloid leukemia (AML) cells in 13/14 cases, as determined by 3H-thymidine (3H-TdR) incorporation and cell counts. Stimulatory activity was significantly greater than in the presence of GM-CSF and was comparable to that of granulocyte colony-stimulating factor (G-CSF), interleukin 3 (IL-3), and 5637 cell line supernatant (SN). Conversely, the ability of SCF to induce primary colony formation by AML clonogenic cells (CFU-L) was lower than that of granulocyte-macrophage colony-stimulating factor (GM-CSF) and 5637 SN in all but four cases. However, SCF potentiated the stimulatory effect of GM-CSF, G-CSF, and IL-3 on both 3H-TdR incorporation and colony formation. In a 7-day liquid culture SCF enhanced CFU-L recovery in all cases to a significantly greater extent than the other growth factors. A further increment was obtained by combinations of SCF with GM-CSF, G-CSF, or IL-3, and this was significantly more effective than 5637 SN. SCF did not induce leukemic cell differentiation. Human recombinant SCF is therefore highly efficient in stimulating AML cell proliferation and expanding the CFU-L pool. It was not, however, able to support long-term growth of AML cells (beyond 2-7 weeks) in five cases tested.

Stem cell factor improvement of proliferation and maintenance of hemopoietic progenitors in myelodysplastic syndromes.

Human recombinant stem cell factor (rSCF) was tested for its capability of improving the defective growth of hemopoietic progenitors in 28 cases of myelodysplastic syndromes (MDS). In vitro growth and response to rSCF were quite variable. However, in most cases, rSCF stimulated CFU-GM growth induced by rG-CSF, rGM-CSF, rIL-3, 5637 conditioned medium (50-1400% enhancement). rSCF effect was slightly more evident on day 14 CFU-GM and in the presence of rIL-3. BFU-E growth induced by rEPO or rIL-3 + rEPO was enhanced by rSCF in about 50% of cases, in linear correlation with the levels of patients' hemoglobin. rSCF did not increase CFU-E growth, whereas it slightly stimulated CFU-Mk in 33% of the cases. EPO, SCF and, particularly, their combination, enhanced the recovery of normal CFU-E and BFU-E after 7 days of liquid culture. This was less evident in cultures of MDS patients. Conversely, CFU-GM generation in long term liquid cultures, although highly variable, was stimulated by rSCF and, above all, by rSCF + rG-CSF, similarly to what was observed with normal bone marrow samples. SCF seems to enhance in vitro erythropoiesis only in MDS cases presenting without severe anemia. It has little effect on megakaryocytopoiesis, while it seems to be more active on CFU-GM growth and maintenance.

Point mutations of the BCL-6 gene: clinical and prognostic correlation in B-diffuse large cell lymphoma.

Although point mutations of the 5' noncoding regions of the BCL-6 proto-oncogene are frequently detected in B-diffuse large cell lymphoma (B-DLCL), a thorough analysis of the clinical correlation of these mutations has not been performed to date. In this study, BCL-6 mutations were examined by DNA direct sequencing in 103 patients with B-DLCL. BCL-6 mutations were found in 53/103 patients, including 38/76 treated with standard chemotherapy and 15/27 treated with autologous stem cell transplantation (ASCT) up front. The presence of BCL-6 mutations was correlated with clinical features at diagnosis and outcome. Mutated patients had a significantly higher LDH level (66% vs 38%, P < 0.05), and bulky disease (51% vs 32%, P = 0.05). In the whole series of patients BCL-6 mutations did not affect CR and OS. Patients with BCL-6 mutations tended to have a prolonged 5-years DFS and FFS compared to those without mutations (DFS 82% vs 63%, FFS 63% vs 49%). Among B-DLCL treated with standard chemotherapy, mutated patients showed a significantly improved 5-year DFS (85% vs 61%, P < 0.05) and, notably, the only four relapses observed among mutated patients occurred in less than 8 months. The multivariate regression analysis (P < 0.01) with DFS as endpoint confirmed the independent prognostic value of BCL-6 mutations. There was a trend for 5-year failure-free survival to be better for patients with BCL-6 mutations (63% vs 43%, P = 0.09). In the 27 patients treated with ASCT, BCL-6 mutations did not correlate with outcome. These results suggest that BCL-6 mutations may predict a higher chance of being free of disease in B-DLCL treated with standard chemotherapy. Larger series of patients need to be analyzed to evaluate the clinical relevance of BCL-6 mutations properly.

Long-term outcome of chronic myeloid leukemia patients treated frontline with imatinib.

For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients.

Long-term results of the GIMEMA VEL-03-096 trial in MM patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival.

Polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis is a useful prognostic tool in multiple myeloma (MM), although its long-term impact still needs to be addressed. This report presents the updated results of the GIMEMA-VEL-03-096 trial. Thirty-nine MM patients receiving bortezomib-thalidomide-dexamethasone after autologous transplantation were monitored for MRD by both nested and real-time quantitative-PCR until relapse. Our data confirm the strong impact of MRD on survival: overall survival was 72% at 8 years median follow-up for patients in major MRD response versus 48% for those experiencing MRD persistence (P=0.041). In addition, MRD kinetics resulted predictive for relapse: indeed median remission duration was not reached for patients in major MRD response, 38 months for those experiencing MRD reappearance and 9 months for patients with MRD persistence (P<0.001). Moreover: (1) 26 patients achieving major MRD response (67%) benefit of excellent disease control (median TNT: 42 months); (2) MRD reappearance heralds relapse, with a TNT comparable to that of MRD persistence (9 versus 10 months, P=0.706); (3) the median lag between MRD reappearance and need for salvage treatment is 9 months. These results suggest the usefulness of a long-term MRD monitoring in MM patients and the need for maintenance or pre-emptive treatments ensuring durable responses.

Managing chronic myeloid leukaemia in the elderly with intermittent imatinib treatment.

The aim of this study was to investigate the effects of a non-standard, intermittent imatinib treatment in elderly patients with Philadelphia-positive chronic myeloid leukaemia and to answer the question on which dose should be used once a stable optimal response has been achieved. Seventy-six patients aged ⩾65 years in optimal and stable response with ⩾2 years of standard imatinib treatment were enrolled in a study testing a regimen of intermittent imatinib (INTERIM; 1-month on and 1-month off). With a minimum follow-up of 6 years, 16/76 patients (21%) have lost complete cytogenetic response (CCyR) and major molecular response (MMR), and 16 patients (21%) have lost MMR only. All these patients were given imatinib again, the same dose, on the standard schedule and achieved again CCyR and MMR or an even deeper molecular response. The probability of remaining on INTERIM at 6 years was 48% (95% confidence interval 35-59%). Nine patients died in remission. No progressions were recorded. Side effects of continuous treatment were reduced by 50%. In optimal and stable responders, a policy of intermittent imatinib treatment is feasible, is successful in about 50% of patients and is safe, as all the patients who relapsed could be brought back to optimal response.

CD9 antigen on acute non-lymphoid leukemia cells: preferential expression by promyelocytic (M3) subtype.

A monoclonal antibody (S17-12), previously described to recognize subsets of myelomonocytic cells, is demonstrated to bind CD9 antigen, a surface marker of B-cell precursors, platelets and several non-hematopoietic tissues. The proportion of S17-12, CD9-positive leukemic cells was determined in 102 patients with acute non-lymphocytic leukemia. It was found to be above 75% in 14/22 M3 cases (including 3/3 of microgranular variant) and only in 1/80 cases of different FAB subtype. Complete reactivity (greater than 95%) of leukemic clonogenic cells with CD9 MoAB was restricted to 4/18 M3 cases. Therefore, a high proportion of CD9-positive cells seems to be peculiar to M3 cases. This may help in the diagnosis of cases that lack typical morphological features.

Suppression of in vitro maintenance of non-promyelocytic myeloid leukemia clonogenic cells by all-trans retinoic acid: modulating effects of dihydroxylated vitamin D3, alpha interferon and 'stem cell factor'.

In a liquid culture system, all-trans retinoic acid (ATRA), alone and in combination with dihydroxylated vitamin D3 (D3) or alpha interferon (alphaIFN) at concentrations achievable in vivo, could significantly suppress the maintenance of non-promyelocytic myeloid leukemia clonogenic cells (CFU-L) in 9/20, 9/18 and 7/11 cases, respectively. That suppression was counteracted only slightly by the addition of 'stem cell factor', a cytokine which promotes CFU-L expansion in vitro. Differentiated cells slightly increased in 5/17 cases only, suggesting the prevalence of anti-proliferative rather than differentiating mechanisms. The present results extend our previous ones and suggest the possible therapeutical value of ATRA+D3 or alphaIFN, even in cases of non-promyelocytic myeloid leukemia.

Establishment from an adult leukemic patient of two novel precursor B cell lines with different growth modality.

Two novel cell lines, PC-53 and PC-53A were established from an adult ALL patient, at third relapse and in the terminal accelerated phase respectively. Both lines displayed the phenotype of B-cell precursors (CD19+, CD38+, CD20-, cytoplasmic-mu-, immunoglobulin gene rearrangement), identical to the freshly isolated blast cells. Chromosomal analysis showed a prominent 45-XX karyotype, including three marker chromosomes. No chromosome 8 abnormalities were detectable, consistently with a non-rearranged c-myc locus. Both cell lines were EBV-negative. Growth stimulation by autologous supernatant was observed for PC-53 cells during the first 4 months in culture, whereas it was much less evident for PC-53A cells. Thus, PC-53 and PC-53A cells represent a useful tool to investigate the mechanisms involved in the clonal expansion of B-cell precursors.

Autologous bone marrow transplantation in acute myeloid leukemia after in-vitro purging with an anti-lacto-N-fucopentaose III antibody and rabbit complement.

Two AML patients, whose leukemic clonogenic cells totally reacted to the anti-lactofucopentaose III S4-7 monoclonal antibody (MoAb), underwent autologous bone marrow transplantation, in first complete remission, after in-vitro purging with S4-7 MoAb and complement. After ablative chemotherapy (BAVC regimen) and reinfusion of S4-7 purged cells, regeneration of marrow cells occurred with prompt recovery of granulopoiesis and erythropoiesis. A more delayed platelet recovery was observed. The two patients are in complete remission at 20 and 11 months from ABMT. The results indicate that immunologic purging with S4-7 MoAb is safe and suitable for selected AML patients undergoing ABMT.

Combined differentiating therapy for myelodysplastic syndromes: a phase II study.

An in vitro synergism between different inducers of AML cell differentiation has been previously observed. Therefore, we treated 53 myelodysplastic (MDS) patients with a low dose combination of cis-retinoic acid (cRA, 20-40 mg/day) and 1,25 alpha (OH)2 cholecalciferol [(OH)2D3, 1-1.5 micrograms/day] +/- intermittent 6-thioguanine (30 mg/m2/day). The latter was reserved for patients with bone marrow (BM) blast excess (> or = 5%). The treatment was well tolerated, without major toxicity. Among 25 patients with BM blasts less than 5%, we observed one complete, eight partial and four minor responses (response rate 52%) with a median response duration of 8 months (2 +/- 24). Median survival, which did not correlate with response, is projected at 76 months. Thirty-one patients with BM blast excess (> or = 5%), including three of the previous group who progressed to refractory anemia with excess of blasts (RAEB), were treated with the three-drug protocol. One complete, 12 partial and six minor responses were obtained (response rate 61%) with a median response duration of 6 months (2-29+). A significant difference in survival (P < 0.005) was observed between the 19 responders (median 25 months) and the 12 non-responders (median 9 months). A reduction in the transfusion need was observed in 41% of the transfusion-dependent patients with blast excess and in 53% of those without blast excess. Therefore, combined differentiating therapy seems more effective than previously reported single agent treatments and should be considered for a larger randomized study to assess its actual impact on survival of MDS patients.

Monoclonal antibody purging and autologous bone marrow transplantation in acute myelogenous leukemia in complete remission.

A mouse monoclonal antibody (S4-7) reacting with human myelomonocytic cells has been previously shown to be suitable for bone marrow purging in selected acute myelogenous leukemia (AML) patients with S4-7 positive leukemic clonogenic cells at diagnosis. The results obtained in seven AML patients who underwent such a treatment, followed by autologous bone marrow transplantation (ABMT), are now reported. Six patients underwent ABMT in first complete remission (CR), one in second CR, after BAVC conditioning regimen. One patient died of infection 1 month after ABMT; in the other six a complete recovery of hemopoiesis was observed. In spite of S4-7 reactivity with normal myelomonocytic cells, a prompt recovery of granulopoiesis was however observed both in in vitro liquid culture and in vivo with a median time of 20 days to reach granulocyte values of 500 x 10(6)/l. The patient transplanted in 2nd CR relapsed 3 months after ABMT. Of the five evaluable patients transplanted in 1st CR, two relapsed 8 and 9 months post-ABMT while three remain in continuous CR at 35, 47, 57 months. Leukemic cells of two of the three patients with recurrent disease were studied at relapse and in both could be detected a significant percentage of S4-7 negative cells, detectable neither at diagnosis nor (one patient) at the time of first relapse after standard chemotherapy.

Role of whole-body [18F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and conventional techniques in the staging of patients with Hodgkin and aggressive non Hodgkin lymphoma.

PURPOSE: The aim of this study was to evaluate the role of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the staging of Hodgkin's and aggressive non-Hodgkin's lymphoma (HL and NHL), comparing it with conventional diagnostic methods, i.e. contrast-enhanced CT and bone marrow biopsy. MATERIALS AND METHODS: Sixty-five consecutive patients (30 HL and 35 NHL) who underwent conventional disease staging and FDG-PET/CT were included. Concordance between conventional methods and PET was established when both procedures identified the same disease stage. Discordant findings were investigated further by using other diagnostic techniques (ultrasonography or magnetic resonance imaging) and/or clinical follow-up. RESULTS: PET correctly staged 93.8% of enrolled patients (61/65), whereas conventional techniques correctly staged 89.2% (58/65; p=NS, Chi(2) test). There was complete concordance in 54/65 patients (83.1%); among the remaining 11 cases, PET upstaged eight patients (seven true positive and one false positive), and downstaged three (all false negative). In 5/65 patients, chemotherapy treatment was modified on the basis of PET findings. CONCLUSIONS: Our data confirm the high accuracy of FDG-PET/CT in staging HL and NHL. FDG-PET/CT should therefore be used routinely in the initial evaluation of both patient subgroups.

Cyclic neutropenia and severe hypogammaglobulinemia in a patient with excess of CD8-positive T lymphocytes: response to G-CSF therapy.

Cyclic neutropenia is a rare hematological disorder characterized by periodical severe granulocytopenia. A stem cell defect and/or immunological abnormalities are considered to play a role in this disease. Here we describe the case of an adult woman who was diagnosed as having both cyclic neutropenia and severe hypogammaglobulinemia. Her clinical history revealed that one or both abnormalities had been present since childhood. Normal in vitro growth of the patient's bone marrow CFU-GM was observed, while immunological analysis revealed the presence of a persistent excess of activated (HLA-DR+) CD8+ T lymphocytes in both bone marrow and peripheral blood. These T lymphocytes have been shown to be polyclonal by DNA analysis, and their role in determining the clinical picture of our patient remain uncertain since they could not be shown to produce inhibitors of in vitro CFU-GM growth. Intermittent low doses of human recombinant G-CSF were able to improve neutropenia and completely prevent infectious symptoms, thus confirming the efficacy of this cytokine in cyclic neutropenia patients.

Revisiting the prognostic role of gallium scintigraphy in low-grade non-Hodgkin's lymphoma.

The purpose of this study was threefold: to evaluate the role of gallium-67 scintigraphy in the staging of low-grade non-Hodgkin's lymphomas (LGNHL), to assess the relationship between the expression of CD71 on the surface of the neoplastic cells and the 67Ga uptake by the tumour, and to establish the contribution of 67Ga scan in defining the prognosis of LGNHL. Forty-eight patients with untreated LGNHL diagnosed in a single institution over a decade were reviewed. The end point of the study was survival of the patients according to the scintigraphic 67Ga score at diagnosis. In addition to 67Ga scan, other prognostic variables were studied, relating to the neoplastic burden, the biology of the tumour and the host. Univariate and multivariate analyses were used. 67Ga scan identified only 116/286 (41%) nodes involved by lymphoma that were detected by clinical examination or computed tomography scan. A scintigraphic scoring system with an arbitrary cut-off value of 3 (high scan score) was able to predict patients with a dismal prognosis: with a mean follow-up of 47 months (range: 1-146 months) the median survival time was 28 months in patients with a high scan score and 74 months in patients with a low scan score (P=0.002). CD71 values were 27. 4%+/-14.9% (mean +/-SD) in the former and 8.9%+/-7.2% in the latter (P=0.0001). Only performance status and extranodal sites were significant variables for prognosis in multivariate analysis. It is concluded that 67Ga scan is inaccurate in staging but might be very important in defining the prognosis in LGNHL, in association with other prognostic variables.