The expression of Ki-67 and Bcl-2 in hodgkin’s lymphoma: Correlation with the international prognostic score and bulky disease

2007 ◽  
Vol 24 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Ljubomir R. Jakovic ◽  
Biljana S. Mihaljevic ◽  
Maja D. Perunicic Jovanovic ◽  
Andrija D. Bogdanovic ◽  
Vesna M. Cemerikic Martinovic ◽  
...  
Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5004-5004
Author(s):  
Ibraheem H Motabi ◽  
Syed Ziauddin A. Zaidi ◽  
Shahid Iqbal ◽  
Atta Munawar Gill ◽  
Imran Khan Tailor ◽  
...  

Abstract The International Prognostic Score (IPS) is the standard stratification system for survival in patients with classical Hodgkin's lymphoma (cHL). However, the IPS only applies to patients with advanced stage disease and it does not offer risk stratification for classical Hodgkin's lymphoma patients diagnosed with limited disease [i.e., stages I and IIA, without constitutional symptoms and no bulky disease. Furthermore, early interim positron emission tomography (PET) has been shown to have a prognostic value superior to that of the IPS in patients with advanced-stage cHL in an analysis (Gallamini et al). Lymphopenia (<600/ul), monocytosis >750 per ul (Tadmore et al) and high tumor-associated macrophages (TAM) are reported to be negative prognostic factors for survival in classical Hodgkin's lymphoma (Koh et al). More recent studies suggested a prognostic role for the peripheral blood absolute lymphocyte count/absolute monocyte count (ALC/AMC) ratio at diagnosis in cHL patients treated with multitude of chemotherapies (Porrata et al, Tadmor et al). It is intriguing to investigate the significance of the ALC/AMC ratio in relation to PET negativity after treatment. Out of 164 cases of cHL treated at our center with ABVD +/- radiation therapy, we identified 70 patients who were evaluated by PET Scan. Median age was 26 years (range 14-80), 33 (47%) were stage IV, Median IPS was 3 (range1-6). We tested correlation of a high ALC/AMC ratio (>2.1) with achievement of a negative PET scan after ABVD chemotherapy. We arbitrarily chose cut-off value of >2.1 (Tadmore et al) from the multiple values reported recently, as this multicenter study had the largest number of patients. A total of 45 patients achieved a negative PET scan. Mean ALC/AMC ratio was 2.39 (range0.19-14.6). ALC/AMC ratio of >2.1 did show a trend for better OS in addition to a negative PET scan. A Spearman correlation test of a negative PET result showed a positive correlation with ALC/AMC ratio of >2.1 though it was weak. This study suggests that the ALC/AMC ratio may be a simple, inexpensive, and independent prognostic factor in cHL outcome and may have a role in the stratification of cHL patients in addition to the International Prognostic Score, TAM content and acheivement of a negative PET scan early post chemotherapy. However we plan to define our own best cut off value for ALC/AMC ratio by ROC and AUC analysis as ALC/AMC Ratio of ≥2.1 did not discriminate survival advantage very well and it may be a reason for weaker correlation with likelihood of a negative PET. Further larger studies are needed to confirm our findings. Disclosures No relevant conflicts of interest to declare.


2012 ◽  
Vol 30 (27) ◽  
pp. 3383-3388 ◽  
Author(s):  
Alden A. Moccia ◽  
Jane Donaldson ◽  
Mukesh Chhanabhai ◽  
Paul J. Hoskins ◽  
Richard J. Klasa ◽  
...  

Purpose The International Prognostic Score (IPS) is the most widely used risk stratification index for Hodgkin's lymphoma (HL). It is based on patients treated before 1992 and predicts 5-year freedom from progression (FFP) and overall survival (OS) ranging from 42% to 84% and 56% to 89%, respectively. The IPS has not been validated in a recently treated population in which outcomes have improved compared with historic results. Patients and Methods By using the British Columbia Cancer Agency Lymphoid Cancer Database, we identified all patients age ≥ 16 years newly diagnosed with advanced-stage HL (stage III to IV, or stage I to II with “B” symptoms or bulky disease ≥ 10 cm) from 1980 to 2010, treated with curative intent with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or an ABVD-equivalent regimen with complete clinical information. Results In all, 740 patients were identified. Five-year FFP and OS were 78% and 90%, respectively. The IPS was prognostic for both FFP (P < .001) and OS (P < .001), with 5-year FFP ranging from 62% to 88% and 5-year OS ranging from 67% to 98%. Analysis limited to patients age 16 to 65 years (n = 686) demonstrated a narrower range of outcomes, with 5-year FFP ranging from 70% to 88% and 5-year OS ranging from 73% to 98%. Conclusion The IPS remains prognostic for advanced-stage HL, but the range of outcomes has narrowed considerably. This improvement in outcome with ABVD should be acknowledged before consideration of alternate initial therapies and when comparing results from current trials with those of historic controls.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1454-1454
Author(s):  
Santiago Pavlovsky ◽  
Claudia Corrado ◽  
Miguel A Pavlovsky ◽  
Virginia Prates ◽  
Lucia Zoppegno ◽  
...  

Abstract Background: The prognostic score for Hodgkin’s lymphoma was defined as the number of adverse prognostic factors presented at diagnosis. Seven factors had similar independent prognostic effects. This model was validated retrospectively in advanced disease using different therapeutic approaches (D Hasenclever et al N Eng J Med339:1506–14, 1998). Methods: From December 1996 up to October 2005, the GATLA completed a risk-adapted therapy with ABVD and IFRT. Patients with stages I-IIIA without bulky disease, who achieved complete remission (CR) after three cycles of ABVD, favorable group (FG) received only IFRT 25 GY to areas of &gt;2 cm at diagnosis. Patients with FG not in CR after three cycles of ABVD, slow responders (FGSR), all stages IIIB-IV and all bulky disease, unfavorable group (UG) received six cycles of ABVD and IFRT 30 GY at remaining areas after 3 cycles of ABVD. A total of 584 patients, completed therapy; of them 513 were evaluated with the IPS. Patients were divided in three groups according to the number of adverse prognostic factors 0–1, 2–3, and ≥ 4. Results: The number of patients, complete remission (CR) rate, event-free survival (EFS) and overall survival (OSV) at 5 years according to prognostic factors in the 513 patients were as follows: IPS # patients (%) # CR (%) % EFS % OSV 0–1 224 (44) 217 (97) 86 95 2–3 241 (47) 213 (88) 73 90 ≥4 48 (9) 40 (83) 65 72 P&lt; 0.020 0.001 0.001 A total of 200 patients with FG had a 5 years EFS and OSV of 89% and 98% while 53 patients with FGSR had an EFS and OSV of 66% and 88% respectively (P&lt;0.001). The IPS in FG and FGSR was 0–1 of 61% versus 49%, 2–3 of 38.5% versus 43% and ≥4 of 0.5% versus 8% respectively (p=0.003). In UG with an EFS and OSV of 72% and 87%, the incidence of IPS 0–1 was 29%, 2–3 was 54% and ≥4 was 17%. Conclusion: The IPS is an excellent tool to predict outcome. Patients with stages I-IIIA without bulky tumour who did not achieve CR after three cycles of ABVD (FGSR) had poorer IPS than FG. In spite of receiving six cycles of ABVD, those with FGSR instead of three of those with FG had statistically a poor outcome. In the PET-TC era, patients who remain positive after three cycles of ABVD will need an intensified therapy with the purpose of improving the bad prognosis.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4436-4436
Author(s):  
Patricia Validire ◽  
Christophe Fermé ◽  
Pauline Brice ◽  
Marine Diviné ◽  
Jean Gabarre ◽  
...  

Abstract The aim of this study was to assess the efficacy of a gemcitabine-based regimen in pretreated Hodgkin’s lymphoma (HL) patients. Relapsed or refractory HL patients treated with gemcitabine, used alone or in combination with other cytotoxic agents, were retrospectively reviewed. Fifty-five patients were included in the study. Initial characteristics before gemcitabine administration were: Ann Arbor stage III–IV: 84%; International Prognostic Score less than 3 in 20/43 cases (47%); thirty-one primary refractory patients at the end of first-line therapy (56%); median number of previous chemotherapy regimens of 3. Twenty-nine patients received gemcitabine alone with a median starting dose of 750 mg/m2 per injection (range: 180–1250 mg/m2); Gemcitabine was administered at a starting dose of 1000 mg/m2 per injection (range: 500–1250) in combination with vinorelbine in 10 patients, oxaliplatin in 13 patients, and other drugs in 3 patients, with a median of 6 injections (range: 1–18). Overall response rate was 20% with 11% of complete remission. On univariate analysis, two adverse factors at progression were significant for response to gemcitabine-based regimen: stage III–IV disease and hemoglobin level less than 10.5 g/dl. In conclusion, the two identified prognostic factors for response to gemcitabine are part of the International Prognostic Score of HL, suggesting that response to gemcitabine is mainly influenced by the specific prognostic factors of HL. Moreover, with an ORR of 29%, our results of the gemcitabine administered alone regimen are not different from those reported in the literature. In contrast, the results of the various series of HL patients treated by gemcitabine-combined regimens, mainly with cisplatin or derivatives, vinorelbine, ifosfamide, doxorubicin, and prednisone, are very different due to different patient characteristics. In heavily pretreated cases, as in our study, the ORR was 26%; inversely, in patients who had received only one or two lines of chemotherapy, the ORR varied between 64% and 82% with 9% to 54% of complete remissions. This discordance can probably be explained by the prognostic impact of previous treatment lines in the response to gemcitabine. This observation emphasizes the possible interest of using gemcitabine earlier in the treatment of Hodgkin’s lymphoma, namely at the time of first relapse or after first-line treatment in primary refractory HL patients.


2007 ◽  
Vol 25 (24) ◽  
pp. 3746-3752 ◽  
Author(s):  
Andrea Gallamini ◽  
Martin Hutchings ◽  
Luigi Rigacci ◽  
Lena Specht ◽  
Francesco Merli ◽  
...  

Purpose Starting from November 2001, 260 newly diagnosed patients with Hodgkin's lymphoma (HL) were consecutively enrolled in parallel Italian and Danish prospective trials to evaluate the prognostic role of an early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) scan and the International Prognostic Score (IPS) in advanced HL, treated with conventional ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy. Patients and Methods Most patients (n = 190) presented with advanced disease (stages IIB through IVB), whereas 70 presented in stage IIA with adverse prognostic factors. All but 11 patients were treated with standard ABVD therapy followed by consolidation radiotherapy in case of bulky presentation or residual tumor mass. Conventional radiologic staging was performed at baseline. FDG-PET scan was performed at baseline and after two courses of ABVD (PET-2). No treatment change was allowed on the basis of the PET-2 results. Results After a median follow-up of 2.19 years (range, 0.32 to 5.18 years), 205 patients were in continued complete remission and two patients were in partial remission. Forty-three patients progressed during therapy or immediately after, whereas 10 patients relapsed. The 2-year progression-free survival for patients with positive PET-2 results was 12.8% and for patients with negative PET-2 results was 95.0% (P < .0001). In univariate analysis, the treatment outcome was significantly associated with PET-2 (P < .0001), stage IV (P < .0001), WBC more than 15,000 (P < .0001), lymphopenia (P < .001), IPS as a continuous variable (P < .0001), extranodal involvement (P < .0001), and bulky disease (P = .012). In multivariate analyses, only PET-2 turned out to be significant (P < .0001). Conclusion PET-2 overshadows the prognostic value of IPS and emerges as the single most important tool for planning of risk-adapted treatment in advanced HL.


2022 ◽  
pp. 7-15
Author(s):  
T. I. Bogatyreva ◽  
A. O. Afanasov ◽  
A. Yu. Terekhova ◽  
N. A. Falaleeva

Rationale. In the early stages of classical Hodgkin’s lymphoma (cHL), the cure rate reaches 85–95 %, but the long-term effects of therapy can worsen overall survival. Current trials for early stages of Hodgkin’s lymphoma with favorable prognosis address the task of maintaining cure rates while reducing sequelae. For early unfavorable stages, the challenge is to improve cure rate without increasing toxicity.Purpose. To assess the potential significance of individual risk factors for optimal choice of the first line chemotherapy in early-stage Hodgkin lymphoma.Materials and methods. This single-center retrospective study included 290 patients with early stage cHL who had received ABVD – based (n = 249; 86 %) or BEACOPP‑21 – based (n = 41; 14 %) combined modality therapy from 2000 to 2017. Progression-free survival (PFS) and overall survival (OS) were assessed in Cox regression analysis including 12 clinical parameters.Main results. At a median follow up of 60 months for the entire group, OS was 95 % and PFS was 89 %. In a multivariate analysis PFS, at 5 years, was significantly inferior in patients with mediastinal bulk, baseline lymphocytopenia (≤ 0.6 × 109/L, р = 0.002; < 1.0 × 109/L, р = 0.000) and male gender; OS was inferior only in patients with an absolute lymphocytopenia (AL). In patients with AL, PFS after ABVD-based regimen was, respectively, 12 % in the high-risk group with mediastinal bulk and 56 % without it. PFS of patients without AL when treated with ABVD did not differ compared to BEACOPP‑21 within the same prognostic group: 95.2 % vs. 92.3 % for non-bulky and 86.4 % vs. 84.2 % for bulky disease. In the absence of AL, mediastinal bulk remained the main and only risk factor in multivariate analysis.Conclusions. The ABVD regimen is highly effective in the first line of chemotherapy for cHL, except for cases with baseline lymphocytopenia, in which the early usage of the BEACOPP regimen in the escalated or 14-day variants might be justified. In patients with mediastinal bulk, standard chemotherapy is not effective enough even in the absence of AL; therefore, if an intermediate PET/CT scan is available, it seems more appropriate to use a milder ABVD regimen on the first line and leave intensive therapy for patients with proven refractory disease. Prospects for improving the efficiency are opened with the new N-AVD and A-AVD schemes, the benefits of which should be evaluated, first of all, in patients with AL and mediastinal bulk.


Blood ◽  
1990 ◽  
Vol 75 (9) ◽  
pp. 1841-1847 ◽  
Author(s):  
HC Schouten ◽  
WG Sanger ◽  
DD Weisenburger ◽  
J Anderson ◽  
JO Armitage

Abstract We describe the chromosomal abnormalities found in 104 previously untreated patients with non-Hodgkin's lymphoma (NHL) and the correlations of these abnormalities with disease characteristics. The cytogenetic method used was a 24- to 48-hour culture, followed by G- banding. Several significant associations were discovered. A trisomy 3 was correlated with high-grade NHL. In the patients with an immunoblastic NHL, an abnormal chromosome no. 3 or 6 was found significantly more frequently. As previously described, a t(14;18) was significantly correlated with a follicular growth pattern. Abnormalities on chromosome no. 17 were correlated with a diffuse histology and a shorter survival. A shorter survival was also correlated with a +5, +6, +18, all abnormalities on chromosome no. 5, or involvement of breakpoint 14q11–12. In a multivariate analysis, these chromosomal abnormalities appeared to be independent prognostic factors and correlated with survival more strongly than any traditional prognostic variable. Patients with a t(11;14)(q13;q32) had an elevated lactate dehydrogenase (LDH). Skin infiltration was correlated with abnormalities on 2p. Abnormalities involving breakpoints 6q11–16 were correlated with B symptoms. Patients with abnormalities involving breakpoints 3q21–25 and 13q21–24 had more frequent bulky disease. The correlations of certain clinical findings with specific chromosomal abnormalities might help unveil the pathogenetic mechanisms of NHL and tailor treatment regimens.


Sign in / Sign up

Export Citation Format

Share Document