Twenty years of MOPP therapy for Hodgkin's disease.

1986 ◽  
Vol 4 (9) ◽  
pp. 1295-1306 ◽  
Author(s):  
D L Longo ◽  
R C Young ◽  
M Wesley ◽  
S M Hubbard ◽  
P L Duffey ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Complete Response ◽  
Results Of Treatment ◽  
End Of Treatment ◽  
Hodgkin's Lymphomas ◽  
Higher Doses ◽  
Disease Free

The results of treatment of 198 patients with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) for Hodgkin's disease were analyzed after a median of 14 years of follow-up. Throughout the period of follow-up, 103 patients have remained continuously free of disease. Review of biopsy specimens of 43 patients originally classified as Hodgkin's disease, lymphocyte-depleted type, revealed that ten of these patients actually had diffuse immunoblastic or large cell non-Hodgkin's lymphomas. Of the 188 patients with Hodgkin's disease, 157 achieved a complete response (CR) (84%), and 66% of them (101 patients) have remained disease-free more than 10 years from the end of treatment. Absence of B symptoms and receiving higher doses of vincristine were factors associated with a higher CR rate and longer survival. Patients entering complete remission in five cycles or less had significantly longer remissions than those requiring six or more cycles. Forty-eight percent of the Hodgkin's disease patients have survived between 9 and 21 years (median, 14 years) from the end of treatment. Nineteen percent of the CRs have died of intercurrent illnesses, free of Hodgkin's disease.

Radiotherapy with curative intent: an option in selected patients relapsing after chemotherapy for advanced Hodgkin's disease.

1987 ◽  
Vol 5 (4) ◽  
pp. 550-555 ◽  
Author(s):  
M Roach ◽  
D S Kapp ◽  
S A Rosenberg ◽  
R T Hoppe
Keyword(s):  
Radiation Therapy ◽  
Combination Chemotherapy ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Complete Response ◽  
Curative Intent ◽  
Major Toxicity ◽  
Disease Free ◽  
Advanced Hodgkin’S Disease

Thirteen patients who had relapsed or failed to obtain a complete remission after combination chemotherapy for the treatment of advanced Hodgkin's disease were treated with subtotal or total lymphoid irradiation with curative intent. Twelve of the 13 patients achieved a complete response (CR). Five of the 12 CRs subsequently relapsed at 3, 9, 9, 12, and 19 months. One patient died of leukemia 11 months following radiotherapy. The actuarial relapse-free survival at 1 year was 60%, and six patients (50%) remain disease-free with a median follow-up of 34 months (range, 10 to 115 months) following the completion of radiotherapy. Patients who failed to obtain a CR to their initial chemotherapy, whose chemotherapy CR was of short duration, or who relapsed initially in extranodal sites, tended to have a worse outcome with radiotherapy. Patients who had long disease-free intervals after initial chemotherapy or relapsed only in nodal sites tended to do relatively well. Radiation therapy was well tolerated with no major toxicity. Potentially curative radiation therapy should be considered an option in the management of selected patients who relapse following combination chemotherapy for advanced Hodgkin's disease.

The pathologic and clinical heterogeneity of lymphocyte-depleted Hodgkin's disease.

1986 ◽  
Vol 4 (3) ◽  
pp. 284-294 ◽  
Author(s):  
J A Kant ◽  
S M Hubbard ◽  
D L Longo ◽  
R M Simon ◽  
V T DeVita ◽  
...  
Keyword(s):  
Clinical Features ◽  
Median Survival ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Histologic Diagnosis ◽  
Abdominal Disease ◽  
Hodgkin's Lymphomas ◽  
Nodular Sclerosing

Patients with Hodgkin's disease of the lymphocyte-depleted subtype (LDHD) have been said to have a poor prognosis. However, reports of this subtype are complicated by the fact that the histologic diagnosis of LDHD is often not straightforward, and its distinction from aggressive non-Hodgkin's lymphomas (NHL) can be difficult. We have reviewed our patients with LDHD at the National Cancer Institute (NCI) in light of an additional decade of experience with neoplastic and non-neoplastic conditions mimicking Hodgkin's disease. Of 198 patients who received MOPP (mechlorethamine, vincristine, procarbazine, prednisone) treatment at the NCI for Hodgkin's disease between 1964 and 1976, 43 (22%) were originally classified as LDHD. The initial diagnostic biopsies from 39 of these patients were reviewed and revealed ten with NHL, nine with LDHD, and 13 with nodular sclerosing Hodgkin's disease of the lymphocyte-depleted subtype (NSLD). The other seven patients had Hodgkin's disease without a lymphocyte-depleted component. The NHL patients were further subclassified as diffuse, large-cell (two cases) and large-cell, immunoblastic (eight cases). The pathologic review was done without knowledge of clinical features which were examined after review in the three major subgroups. Of ten patients with NHL, only three had a complete remission (CR), and median survival was 7 months. Nine of the NHL patients presented with features that are unusual for patients with Hodgkin's disease, such as bulky abdominal disease, epitrochlear lymphade-nopathy, or hypercalcemia. CRs were attained by 67% and 85% of patients in the LDHD and NSLD groups, respectively: median survival had not been reached in either group with a median of 14 years of follow-up. Lymphocyte-depleted Hodgkin's disease, adequately treated, is in our limited group of patients no worse than other histopathologic subtypes of Hodgkin's disease. The erroneous inclusion of patients with high-grade NHLs into this subtype of Hodgkin's disease may be one reason for earlier literature reports of its more aggressive nature. The diagnosis of LDHD should be made cautiously, particularly in patients with clinical features that are unusual for Hodgkin's disease at presentation.

scholarly journals Absence of the t(2;5) in Hodgkin's disease [see comments]

Blood ◽  
1995 ◽  
Vol 85 (10) ◽  
pp. 2845-2847 ◽  
Author(s):  
LM Weiss ◽  
JR Lopategui ◽  
LH Sun ◽  
OW Kamel ◽  
CH Koo ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Blot Hybridization ◽  
Southern Blot Hybridization ◽  
Large Cell ◽  
Common Finding ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Hodgkin's Lymphomas

The cytogenetics of Hodgkin's disease (HD) is poorly understood. However, a t(2;5) is a common finding in CD30+ anaplastic large cell lymphoma (ALCL), a neoplasm thought by some to be closely related to HD. Recently, the t(2;5) has been cloned and found to represent fusion of the NPM gene with the ALK gene. Using Southern blot hybridization, one group has reported finding rearrangements of NPM in a proportion of cases of both ALCL and HD. In the current study, we used a highly sensitive reverse transcriptase-polymerase chain reaction methodology to analyze 34 cases of HD for the t(2;5). We were unable to find polymerase chain reaction evidence for the t(2;5) in any of the cases of HD, a result significantly different from our previous study of CD30+ non-Hodgkin's lymphomas (P < .02) including ALCL (P < .04), using identical methods. Our results do not support the hypothesis that the t(2;5) represents a common chromosomal abnormality for both HD and ALCL.

Alternating cycles of combination chemotherapy for patients with recurrent Hodgkin's disease following radiotherapy. A prospectively randomized study by the Cancer and Leukemia Group B.

1986 ◽  
Vol 4 (6) ◽  
pp. 838-846 ◽  
Author(s):  
V Vinciguerra ◽  
K J Propert ◽  
M Coleman ◽  
J R Anderson ◽  
L Stutzman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Combination Chemotherapy ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Disease Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Group B ◽  
Leukemia Group ◽  
Disease Free

A randomized clinical trial of combination chemotherapy for patients who relapsed following primary radiation therapy for Hodgkin's disease was conducted from 1975 to 1981 by the Cancer and Leukemia Group B (CALGB). One hundred thirteen patients were prospectively randomized to receive 12 cycles of either CVPP (CCNU, vinblastine, procarbazine, and prednisone), ABOS (bleomycin, vincristine [Oncovin; Lilly, Indianapolis], doxorubicin [Adriamycin, Adria Laboratories, Columbus, Ohio], and streptozotocin), or alternating cycles of CVPP and ABOS. The median length of observation for patients in this report is 4 years. Toxicities of the three treatment programs were primarily hematologic. Frequencies of complete response were 72% for CVPP, 70% for ABOS, and 82% for CVPP/ABOS (P = .37). Females and patients who had nodular sclerosing disease at initial diagnosis had significantly higher complete response rates. The 5-year disease-free survival for the complete responders was 55%; the 5-year overall survival was 60%. There were no significant differences among the treatments on disease-free survival (P = .78) or overall survival (P = .18). Age under 40 years was the only significant positive prognostic factor for disease-free survival (P = .095) and overall survival (P = .003). This study demonstrates no statistically significant advantage for alternating cycles of combination chemotherapy in affecting complete response frequency, disease-free survival, or overall survival as compared with therapy with CVPP or ABOS alone. However, the power to detect differences in these outcome parameters is somewhat limited by the sample sizes.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Expression of functional CD40 antigen on Reed-Sternberg cells and Hodgkin's disease cell lines

Blood ◽  
1995 ◽  
Vol 85 (3) ◽  
pp. 780-789 ◽  
Author(s):  
A Carbone ◽  
A Gloghini ◽  
V Gattei ◽  
D Aldinucci ◽  
M Degan ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Lines ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Growth Factor Receptor ◽  
Large Cell ◽  
Distinct Pattern ◽  
Histologic Subtype ◽  
Hodgkin's Lymphomas

CD40 is a member of the nerve growth factor receptor family, showing a significant homology to the Hodgkin's disease (HD)-associated antigen CD30 and is capable of transduce growth signals in a number of cell types. A series of 312 lymphoma samples, including 139 cases of HD, 32 cases of CD30+ anaplastic large cell (ALC) lymphomas, 141 cases of other non-Hodgkin's lymphomas (NHLs), and a panel of HD- or NHL-derived cell lines, were evaluated for CD40 expression by immunostaining of paraffin embedded sections, cell smears and flow cytometry. CD40 was strongly expressed with a highly distinct pattern of staining on Reed- Sternberg (RS) cells and variants in 100% (139/139) of HD cases, irrespective of their antigenic phenotype (T, B, non T-non B) and histologic subtype of HD. Conversely, CD40 was immunodetected on only one third (12/32; 37%) of ALC lymphoma cases and on 105 of 127 B-cell NHLs. The relative cell density of CD40 on HD cell lines (L-428, KM-H2, HDLM-2) as assessed by flow cytometry was significantly higher than on all other lymphoma cells analyzed. Engagement of CD40 by its soluble ligand (CD40L) enhanced both clonogenic capacity and colony cell survival of HD cell lines. Such effect was potentiated by interleukin-9 costimulation in KM-H2 cells. Finally, we have shown that in vitro rosetting of activated CD4+ T cells to HD cells (L-428) is mediated in part by the CD40/CD40L adhesion pathway. Our data indicate that CD40 is a useful antigen for immunodetection and identification of tumor cells in all subtypes of HD, and suggest that it may play a role in the regulation of RS cell expansion and the contact-dependent interactions of these cells with cytokine-producing T lymphocytes.

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).

Result of Paediatric Non Hodgkin’s Lymphoma with Intensified Short Duration Chemotherapy : A Result from Eastern India

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4952-4952
Author(s):  
Ashis Mukhopadhyay ◽  
Melissa Adde ◽  
Ian Magrath ◽  
Soma Mukhopadhyay
Keyword(s):  
Short Duration ◽  
Burkitt Lymphoma ◽  
Progressive Disease ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Complete Response ◽  
Cancer Research Institute ◽  
Hodgkin's Lymphomas ◽  
Age Range

Abstract Background: The Non-Hodgkin’s Lymphomas (NHL) in childhood are usually high grade and diffuse histology. They require intensified short duration chemotherapy in contrast to adult NHL. The aim of our study was to observe the result of aggressive short duration chemotherapy in paediatric NHL. Materials & Methods: We included consecutive 160 paediatric NHL patients in paediatric haemato-oncology department of Netaji Subhash Chandra Bose Cancer Research Institute during period from June 1996 to December 2007. The inclusion criteria were patients less than 25 yrs of age with a diagnosis of NHL and Patients are clinically staged according to the St. Jude’s (Murphy’s) classification. Patients with &gt; 25% blasts in the bone marrow were treated as leukemia and excluded from the study. Each patient received 3 cycles A and 3 cycles B of MCP842 protocol of INCTR. Response was assessed at the completion of 2cycles of chemotherapy (1 each of A and B). Result: A total of 160 previously untreated patients were entered in this study. The age range was 1 to 25 yrs (median 13.5). Fourty Eight (48) patients had Lymphoblastic Lymphoma (LL), 64 patients (40%) had Burkitt Lymphoma, 40 (25%) diffuse Large B Cell Lymphoma (DLCL) and 8 (5%) had Anaplastic Large Cell. The abdomen was the most common site (56%) of involvement followed by the mediastinum (15.62%). One hundred and Thirty four (134)(83.75%) patients achieved complete response after 2 cycles of therapy, 14 patients (8.75%) achieved partial response and 6 (3.75%) had no response, 6 (3.75%) were not evaluable. With median follow up of 4 & 1/2 yaers (range 7 months – 10 years) a total of 38 (23.75%)patients (19 LL, 13 Burkitt Lymphoma, 5 DLCL and 1 ALCL) have died. The causes of death were progressive disease in 26 (16.25%), infection in 6 (3.75%), tumour lysis in 4 (2.5%), hepatitis in 1 (0.63%), and unknown 1 (0.63%). One hundred and twenty two (122) patients (76.25%) are alive and in complete remission. The patients tolerated chemotherapy well. Grade IV febrile Neutropenia was seen in 34 patients (21.25%). Conclusion: Result of MCP 842 was promising and we will continue the protocol in future.

Treatment of advanced-stage Hodgkin's disease: alternating noncrossresistant MOPP/CABS is not superior to MOPP.

1991 ◽  
Vol 9 (8) ◽  
pp. 1409-1420 ◽  
Author(s):  
D L Longo ◽  
P L Duffey ◽  
V T DeVita ◽  
P H Wiernik ◽  
S M Hubbard ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Survival Curve ◽  
Disease Free Survival ◽  
Dose Intensity ◽  
Advanced Stage ◽  
Free Survival ◽  
Disease Free

One hundred twenty-five assessable patients with advanced-stage Hodgkin's disease were randomized to receive mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or MOPP alternating with lomustine (CCNU), doxorubicin, bleomycin, and streptozocin (CABS). The median follow-up is 7.7 years. The complete response rate was 60 of 66 MOPP-treated patients (91%) and 54 of 59 MOPP/CABS-treated patients (92%) (difference not significant). The level of the disease-free survival curve at longest follow-up is 65% for MOPP-treated patients and 72% for MOPP/CABS-treated patients (difference not significant). The overall survival at 12 years is projected at 68% for MOPP-treated patients and 54% for MOPP/CABS-treated patients (difference not significant). Thus, there were no significant differences in efficacy between MOPP and MOPP/CABS. However, MOPP/CABS was more emetogenic than MOPP, and four MOPP/CABS-treated patients went on to develop secondary acute leukemia. No MOPP-treated patients developed leukemia. High initial erythrocyte sedimentation rate (ESR) and high platelet counts adversely affected treatment outcome. MOPP-treated patients who received greater than 81% of the projected dose intensity of vincristine over the first three cycles had significantly improved disease-free survival rates over those receiving less than 81%. MOPP/CABS-treated patients who received greater than 82% of the projected dose intensity of vincristine had significantly better overall survival than those who received less than 82%. Disease-free survival on both arms was significantly better in patients who received greater than 84% of the projected dose intensity of all agents. The effect of dose intensity was particularly apparent in patients with poor prognostic factors where those who received greater than 84% of the projected dose intensity of all agents had significantly improved disease-free and overall survival.

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