Anaplastic large-cell lymphoma: clinical and prognostic evaluation of 90 adult patients.

1996 ◽  
Vol 14 (3) ◽  
pp. 955-962 ◽  
Author(s):  
P L Zinzani ◽  
M Bendandi ◽  
M Martelli ◽  
B Falini ◽  
E Sabattini ◽  
...  
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Third Generation ◽  
Bulky Disease ◽  
Free Survival ◽  
The Common ◽  
Large Cell Lymphoma ◽  
Hodgkin's Lymphomas

PURPOSE During the last few years, the application of CD30 monoclonal antibodies has led to the identification of a new lymphoma entity, termed anaplastic large cell lymphoma (ALCL). This tumor includes four distinct histologic subtypes, among which the Hodgkin's-like/Hodgkin's-related one (ALCL-HL) shares morphologic and phenotypic features with Hodgkin's disease (HD). PATIENTS AND METHODS From September 1988 to October 1993, 90 ALCL patients were treated with third-generation chemotherapy regimens (either vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate with leucovorin, and prednisone [F-MACHOP] or methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]) during the course of an Italian multicentric randomized trial on high-grade non-Hodgkin's lymphomas (HG-NHL). In particular, 47 patients had ALCL of the common type (ALCL-CT) and 43 ALCL-HL. Null phenotype was the most common (39.8%), while T-cell, B-cell, and hybrid forms accounted for 35.5%, 22.2%, and 2.5%, respectively. RESULTS Complete remission (CR) was achieved in 66 of 90 (73.5%) patients (33 of 47 [70%] with ALCL-CT and 33 of 43 [77%] with ALCL-HL). The majority of the patients in CR (56.5%) were alive and well at a median follow-up time of 38 months; no significant differences were observed between the two histologic groups, with the rate of complete responders being 49% and 65% in ALCL-CT and ALCL-HL, respectively. The probability of relapse-free survival (RFS), projected at 63 months, was 67% for ALCL-CT and 82% for ALCL-HL. The risk of lower CR and RFS rates was associated with the presence of bulky disease, advanced stage, and B symptoms. CONCLUSION The data of the present study confirm that ALCL responds to third-generation chemotherapy regimens similarly to other aggressive malignant lymphomas in terms of both CR and RFS rates.

Long-term follow-up and analysis for prognostic factors for patients with limited-stage diffuse large-cell lymphoma treated with initial chemotherapy with or without adjuvant radiotherapy.

1989 ◽  
Vol 7 (9) ◽  
pp. 1186-1191 ◽  
Author(s):  
S E Jones ◽  
T P Miller ◽  
J M Connors
Keyword(s):  
Prognostic Factors ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Diffuse Large Cell Lymphoma ◽  
Relapse Free Survival ◽  
Bulky Disease ◽  
Free Survival ◽  
Large Cell Lymphoma

In order to assess long-term outcome of patients with localized (stage I or II) diffuse large-cell lymphoma treated with initial combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without involved-field radiotherapy following chemotherapy, we combined data from two prospective trials in Tucson (64 patients) and Vancouver (78 patients). Follow-up on 142 patients was updated and a variety of potential pretreatment prognostic factors were analyzed for impact on outcome. One hundred forty patients (99%) achieved a complete remission and there were no differences in outcome between institutions. Twenty-three patients have relapsed and 22 have died from lymphoma at a median follow-up of 4.4 years, resulting in an overall relapse-free survival of 82% at 5 years. There was no treatment-related mortality and were no instances of late cardiac toxicity or leukemia. Of the following potential pretreatment prognostic factors (age, stage, "B" symptoms, extranodal disease, gastrointestinal tract involvement, bulky disease, or disease above or below the diaphragm), only stage affected relapse-free survival (RFS) (P = .16) and survival (.003). Among 34% of patients over age 65, outcome was similar to younger patients. RFS for 108 patients treated with CHOP plus radiotherapy was not significantly superior to the use of CHOP alone in 34 patients (P = .2).

Anaplastic large cell lymphoma (ALCL) ALK positive and ALCL ALK negative uniformly treated with intensive alternating chemotherapy at a single institution.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18512-e18512
Author(s):  
Joanna Romejko-Jarosinska ◽  
Katarzyna Domanska-Czyz ◽  
Beata Ostrowska ◽  
Ewa Paszkiewicz-Kozik ◽  
Lidia Poplawska ◽  
...  
Keyword(s):  
Survival Time ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Clinical Stage ◽  
Progression Free Survival ◽  
Large Cell ◽  
Bulky Disease ◽  
Free Survival ◽  
Large Cell Lymphoma ◽  
Alk Positive

e18512 Background: Anaplastic large cell lymphoma ALK positive (ALCL ALK+) is frequently referred to as easily curable disease, however, patients with more than 1 IPI risk factors have a poor outcome. ALCL ALK negative (ALCL ALK-) have usually higher IPI score and there is no general consensus on what treatment is the optimal. We evaluated data on 26 consecutive patients with ALCL ALK+ and ALCL ALK- treated uniformly at our institution between July 2004 and April 2011. Methods: 26 patients with ALCL ALK+ or ALCL ALK- were treated according to GMALL B-ALL/NHL 2002 protocol (Hoelzer D et al. Blood 2007; 110: Abstr. 518) without rituximab. Kaplan-Meier method and Cox’s model were used to analyze overall survival time and progression free survival time. Results: ALK protein expression was tested in 26 patients, 19(73%) were positive, 5(27%) were negative. Median age was 33 years (range 16-53). 14 pts (54%) were male, 20 (77%) were in clinical stage (CS) III or IV, 16 (61,5%) had B symptoms, 10(38,5%) had bulky disease, 10 (38,5%) had LDH > N, and 20 (77%) had IPI score >1. The overall response rate (ORR) was evaluated in 23 of 26 patients. The ORR was 87% (20/23 patients). After median follow up of 26 months (range; 6-90) overall (OS) and progression free survival (PFS) at 2 years was 67%: 95% C.I.=[48%, 86%] and 65%: 95% C.I.=[48%, 82%], respectively. On multivariate analysis none of factors: CS III and IV, B symptoms, bulky disease, IPI score>2, LDH>N, ALK expression influenced OS and PFS. The major toxicity was reversible myelosuppression: grade 4 neutropenia occurred after every cycle. Other complications included mucositis and infection. Two toxic deaths (7,6%) from sepsis occurred during neutropenia after first cycle of treatment. Conclusions: These results suggest that GMALL- B-ALL/NHL 2002 protocol is an effective treatment for both ALCL ALK + and ALCL ALK-, however, toxicity is remarkable, with neutropenia and infection being most frequent complications.

Clinical implications of serum levels of soluble CD30 in 70 adult anaplastic large-cell lymphoma patients.

1998 ◽  
Vol 16 (4) ◽  
pp. 1532-1537 ◽  
Author(s):  
P L Zinzani ◽  
S Pileri ◽  
M Bendandi ◽  
M Buzzi ◽  
E Sabattini ◽  
...  
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Complete Response ◽  
Serum Levels ◽  
Advanced Stage ◽  
Bulky Disease ◽  
Soluble Cd30 ◽  
Large Cell Lymphoma ◽  
Hodgkin's Lymphomas

PURPOSE In the last few years, the search for new biologic markers in high-grade non-Hodgkin's lymphomas has provided important results. In particular, soluble CD30 (sCD30) levels were elevated in most patients with Hodgkin's disease (HD) and anaplastic large-cell lymphoma (ALCL). PATIENTS AND METHODS From September 1988 to October 1993, treatment was completed in 70 previously untreated patients with ALCL, of whom 38 had the common type (ALCL-CT) and 32 had the Hodgkin's-like subtype (ALCL-HL). Serum sCD30 levels were measured at the time of diagnosis and after induction polychemotherapy in all patients; in addition, the initial sCD30 levels were compared with those obtained from 50 stage-matched patients with HD. RESULTS Pretreatment levels of sCD30 were highly elevated in the stage-matched group of HD patients compared with healthy controls; median sCD30 levels in patients with ALCL-CT and ALCL-HL were 18 and seven times higher, respectively, than in patients with HD. The sCD30 level normalized on achievement of complete response (CR). The risk of lower relapse-free survival was associated with bulky disease, advanced stage, and high pretreatment sCD30 levels; the risk of lower overall survival was associated with advanced stage and pretreatment levels of sCD30 in both univariate and multivariate analysis. CONCLUSION The results of this study suggest that sCD30 is a specific prognostic indicator of the risk for lower complete response rate and relapse-free expectancy for patients with ALCL.

Prognostic factors in childhood anaplastic large cell lymphoma: results of a large European intergroup study

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1560-1566 ◽  
Author(s):  
Marie-Cécile Le Deley ◽  
Alfred Reiter ◽  
Denise Williams ◽  
Georges Delsol ◽  
Ilske Oschlies ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Skin Lesions ◽  
Free Survival ◽  
Visceral Involvement ◽  
Increased Risk ◽  
Large Cell Lymphoma ◽  
Mediastinal Involvement

Abstract To study prognostic factors of progression/relapse, data concerning 225 children enrolled between 1987 and 1997 in Berlin-Frankfurt-Münster, Société Française d'Oncologie Pédiatrique and United Kingdom Children's Cancer Study Group prospective studies for the treatment of anaplastic large cell lymphoma (ALCL) were merged. Median follow-up was 9.3 years. Five-year overall survival and event-free survival of the whole population was 81% (95% confidence interval, 76%-86%) and 69% (63%-74%), respectively. B symptoms, mediastinal involvement, skin lesions, visceral involvement, St Jude stage 3-4, Ann Arbor stage 3-4, and elevated lactate dehydrogenase increased the risk of progression/relapse in the univariate analysis. In the multivariate analysis, 3 factors remained significant: mediastinal involvement (relative risk [RR] = 2.1 [1.2-3.5]), visceral involvement defined as lung, liver, or spleen involvement (RR = 2.1 [1.3-3.6]), and skin lesions (RR = 1.9 [1.1-3.2]). Five-year progression-free survival (PFS) of the 81 patients with none of these risk factors was 89% [82%-96%], contrasting with a 5-year PFS of 61% [53%-69%] in the 144 patients with at least 1 risk factor (RR = 4.4 [2.2-8.9; P < .001). In conclusion, 3 factors associated with an increased risk of failure in childhood ALCL have been defined: mediastinal involvement, visceral involvement, and skin lesions.

Primary Cutaneous CD30+ Anaplastic Large Cell Lymphoma: Analysis of the Stanford Series Reveals Two Clinical Subsets of Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4568-4568
Author(s):  
Sunil A. Reddy ◽  
Howard Liu ◽  
Sabine Kohler ◽  
Richard T. Hoppe ◽  
Youn H. Kim
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Body Regions ◽  
Local Disease ◽  
Kaplan Meier ◽  
Large Cell Lymphoma ◽  
Regional Disease ◽  
Multifocal Disease

Abstract Primary cutaneous CD30+ anaplastic large cell lymphoma (PCALCL) represents the malignant end of the spectrum of CD30+ lymphoproliferative disorders. The management of PCALCL is markedly different than that of its primary nodal counterpart. The basis of this difference is due to the less aggressive nature of PCALCL. There is no evidence that chemotherapy is necessary or superior to the excellent results of local therapies such as radiation and/or excision for unilesional or local disease. Even patients with generalized disease have done well in some series. Here we review the characteristics and management of 40 cases of this rare cutaneous lymphoma. We have excluded Lymphomatoid Papulosis (LyP), the benign counterpart of PCALCL. In our series PCALCL was defined as CD30+ ALCL with disease limited to the skin as defined by a negative CT scan. Bone marrow biopsy was not necessary although it was always negative when done. Unilesional, local and extensive regional patients were generally treated with radiotherapy and/or excision, while chemotherapy and biologics were reserved for extensive regional and multifocal patients. The study included 30 men and 10 women with a mean age of 57.5 years (range 24–86). The estimated Kaplan-Meier disease specific survival (DSS) at 4 years for the entire group is 75.6%, with a median follow-up of 27.5 months (1–213). Twenty-six patients presented with unilesional or local disease, while there were 8 multifocal and 6 extensive regional patients (defined as 2 or more lesions beyond a 15 cm2 area apart but limited to 1 or 2 contiguous body regions). The unilesional/local patients had an estimated 4 year DSS of 93%. All but 2 of these patients are alive. The estimated Kaplan-Meier 4 year DSS of patients with either multifocal or extensive regional disease is 30%. Estimated 4 year Kaplan-Meir survival of PCALCL by extent of skin involvement unilesional/local 93% multifocal/extensive regional 30% P-value&lt;0.001 Seven deaths occurred in this series of which 6 were either directly or indirectly attributable to PCALCL. Of the deaths 3 were among the 6 patients with extensive regional disease and 2 were among the 8 patients with multifocal disease. Furthermore, 4 multifocal and 2 extensive regional patients have active disease at the time of last follow-up. Further followup will determine their eventual outcome. The 2 patients with unilesional disease who died, both developed rapid progression to extensive regional disease. Although most patients with PCALCL present with local disease and do quite well with local therapy, it appears that some PCALCL patients with multifocal disease, extensive regional disease, and rapidly progressive unilesional disease behave as high grade lymphomas refractory to standard chemotherapy.

The Cryptic inv(2)(p23q35) Defines a New Molecular Genetic Subtype of ALK-Positive Anaplastic Large-Cell Lymphoma

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2688-2695 ◽  
Author(s):  
Iwona Wlodarska ◽  
Chris De Wolf-Peeters ◽  
Brunangelo Falini ◽  
Gregor Verhoef ◽  
Stephan W. Morris ◽  
...  
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Fusion Gene ◽  
Cell Lymphoma ◽  
Young Male ◽  
Large Cell ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma ◽  
Alk Positive ◽  
Hodgkin's Lymphomas ◽  
Alk Protein

Recently, a distinctive entity characterized by expression of the anaplastic lymphoma kinase (ALK) protein [most frequently due to the t(2;5)(p23;q35)-associated NPM-ALK fusion] has emerged within the heterogenous group of non-Hodgkin’s lymphomas (NHL) classified as anaplastic large-cell lymphoma (ALCL). Sporadic variant 2p23/ALK abnormalities identified in ALK-positive ALCL indicate that genes other than NPM may also be involved in the deregulation of ALK and lymphomagenesis. We report here three cases with an inv(2)(p23q35) detected by fluorescence in situ hybridization (FISH) in young male patients with ALK-positive ALCL. In contrast to ALCL cases with the classical t(2;5)(p23;q35) that usually show both cytoplasmic and nuclear or predominantly nuclear alone localization of the NPM-ALK chimeric product, in all three cases with an inv(2)(p23q35) the ALK protein accumulated in the cytoplasm only, supporting the previous assumption that the oncogenic potential of ALK may not be dependent on its nuclear localization. As the first step to identify theALK partner gene involved in the inv(2)(p23q35), we performed extensive FISH studies and demonstrated that the 2q35 breakpoint occurred within the 1,750-kb region contained within the 914E7 YAC. Moreover, a striking association of the inv(2)(p23q35) with a secondary chromosomal change, viz, ider(2)(q10)inv(2)(p23q35), carrying two additional copies of the putative ALK-related fusion gene, was found in all three patients, suggesting that, in contrast to the standard t(2;5)/NPM-ALK fusion, multiple copies of the putative 2q35-ALK chimeric gene may be required for efficient tumor development. In summary, we demonstrate that the inv(2)(p23q35), a variant of the t(2;5)(p23;q35), is a recurrent chromosomal abnormality in ALK-positive ALCL, the further characterization of which should provide new insight into the pathogenesis of these lymphomas. © 1998 by The American Society of Hematology.

scholarly journals Amplification of genomic DNA demonstrates the presence of the t(2;5) (p23;q35) in anaplastic large cell lymphoma, but not in other non- Hodgkin's lymphomas, Hodgkin's disease, or lymphomatoid papulosis

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1771-1779 ◽  
Author(s):  
AH Sarris ◽  
R Luthra ◽  
V Papadimitracopoulou ◽  
M Waasdorp ◽  
MA Dimopoulos ◽  
...  
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Hodgkin's Disease ◽  
Genomic Dna ◽  
Cell Lymphoma ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Lymphomatoid Papulosis ◽  
Large Cell Lymphoma ◽  
Hodgkin's Lymphomas ◽  
Dna Pcr

Anaplastic large cell lymphoma (ALCL) is a distinct clinicopathologic variant of intermediate grade non-Hodgkin's lymphomas (NHL) composed of large pleomorphic cells that usually express the CD30 antigen and interleukin (IL)-2 receptors, and is characterized by frequent cutaneous and extranodal involvement. With variable frequency ALCL bear the t(2;5)(p23;q35) chromosomal translocation that fuses the nucleophosmin (NPM) gene on chromosome 5q35 to a novel protein kinase gene, Anaplastic Lymphoma Kinase (ALK), on chromosome 2p23. We determined the frequency of this translocation with a novel DNA polymerase chain reaction (PCR) technique using 0.5 microgram of genomic DNA, 5′-primers derived from the NPM gene and 3′-primers derived from the ALK gene and hybridization with internal probes. The presence of amplifiable DNA in the samples was tested with the inclusion in the PCR reaction of oligonucleotide primers designed to amplify a 3016-bp fragment from the beta-globin locus. NMP-ALK fusion amplicons were detected using DNA isolated either from all three ALCL cell lines tested, or from all four primary ALCL tumors known to contain the t(2;5)(p23;q35) translocation. Nested amplicons were detected by hybridization in 100% of specimens diluted 10(4)-fold and in 20% of those diluted 10(5)-fold. We subsequently examined archival genomic DNA from 20 patients with ALCL, 39 with diffuse large cell, 2 with mantle cell, 20 with peripheral T cell, 13 with low-grade NHL, 31 with Hodgkin's disease (HD), and 6 with lymphomatoid papulosis. Fusion of the NPM and ALK genes was detected in three of 18 patients with ALCL who had amplifiable DNA (17%, 95% confidence intervals 4% to 41%), but not in any patients with other NHL, HD, or lymphomatoid papulosis. The amplicon sizes were different in all cell lines and patients reflecting unique genomic DNA breakpoints. We conclude that with genomic DNA-PCR the rearrangement of the NPM and ALK loci is restricted to patients with ALCL. Further studies are needed to determine the prognostic significance of the NPM-ALK rearrangement, to determine whether its detection can aid in the differential diagnosis between ALCL. Hodgkin's disease, and lymphomatoid papulosis, and to establish the usefulness of the genomic DNA PCR in the monitoring of minimal residual disease in those patients whose tumors bear the t(2;5).

The Cryptic inv(2)(p23q35) Defines a New Molecular Genetic Subtype of ALK-Positive Anaplastic Large-Cell Lymphoma

Blood ◽  
1998 ◽  
Vol 92 (8) ◽  
pp. 2688-2695 ◽  
Author(s):  
Iwona Wlodarska ◽  
Chris De Wolf-Peeters ◽  
Brunangelo Falini ◽  
Gregor Verhoef ◽  
Stephan W. Morris ◽  
...  
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Fusion Gene ◽  
Cell Lymphoma ◽  
Young Male ◽  
Large Cell ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma ◽  
Alk Positive ◽  
Hodgkin's Lymphomas ◽  
Alk Protein

Abstract Recently, a distinctive entity characterized by expression of the anaplastic lymphoma kinase (ALK) protein [most frequently due to the t(2;5)(p23;q35)-associated NPM-ALK fusion] has emerged within the heterogenous group of non-Hodgkin’s lymphomas (NHL) classified as anaplastic large-cell lymphoma (ALCL). Sporadic variant 2p23/ALK abnormalities identified in ALK-positive ALCL indicate that genes other than NPM may also be involved in the deregulation of ALK and lymphomagenesis. We report here three cases with an inv(2)(p23q35) detected by fluorescence in situ hybridization (FISH) in young male patients with ALK-positive ALCL. In contrast to ALCL cases with the classical t(2;5)(p23;q35) that usually show both cytoplasmic and nuclear or predominantly nuclear alone localization of the NPM-ALK chimeric product, in all three cases with an inv(2)(p23q35) the ALK protein accumulated in the cytoplasm only, supporting the previous assumption that the oncogenic potential of ALK may not be dependent on its nuclear localization. As the first step to identify theALK partner gene involved in the inv(2)(p23q35), we performed extensive FISH studies and demonstrated that the 2q35 breakpoint occurred within the 1,750-kb region contained within the 914E7 YAC. Moreover, a striking association of the inv(2)(p23q35) with a secondary chromosomal change, viz, ider(2)(q10)inv(2)(p23q35), carrying two additional copies of the putative ALK-related fusion gene, was found in all three patients, suggesting that, in contrast to the standard t(2;5)/NPM-ALK fusion, multiple copies of the putative 2q35-ALK chimeric gene may be required for efficient tumor development. In summary, we demonstrate that the inv(2)(p23q35), a variant of the t(2;5)(p23;q35), is a recurrent chromosomal abnormality in ALK-positive ALCL, the further characterization of which should provide new insight into the pathogenesis of these lymphomas. © 1998 by The American Society of Hematology.

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