Bleomycin-induced pulmonary toxicity in Hodgkin`s lymphoma patients

2020 ◽  
Vol 30 (4) ◽  
pp. 413-420
Author(s):  
S. V. Shakhtarina ◽  
A. A. Danilenko ◽  
N. V. Afanasova ◽  
N. A. Falaleeva ◽  
S. A. Ivanov ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Pulmonary Toxicity ◽  
Clinical Evidence ◽  
Radiation Pneumonitis ◽  
Study Group ◽  
X Rays ◽  
Radiation Fibrosis ◽  
Conventional Film ◽  
Digital Chest

Bleomycin used as part of many chemo-therapeutic programs for treating Hodgkin lymphoma is associated with pulmonary toxicity. Development of complications after mediastinal radiotherapy is also well-known. However, the synergistic effect of the combination of radiotherapy and bleomycin is considered in the literature much less frequently and mainly when using the total focal doses (SOD) of 36 – 40 Gy. Since 1998 the chemo-radiotherapeutic regimens applied to the treatment of Hodgkin lymphoma in the MRRC (Obninsk) has involved subradical TTD of 20 – 30 Gy. The goal of the study is to evaluate pulmonary toxicity in Hodgkin lymphoma patients treated with chemo-radiotherapy involving ABVD and mediastinal treatment with TTD of 20 – 30 Gy.Methods. A series of 142 Hodgkin lymphoma patients received ABVD and mediastinal radiotherapy at the TTD 20 – 30 Gy. Conventional film and digital chest X-rays, linear and digital tomograms taken at different stages of treatment and follow up were analysed.Results. Changes in lungs in the form of a pathologic pulmonary pattern (interstitial pneumonitis) were seen in 39 (27.5%) of 142 patients. In 10 (25.6%) of 39 patients focal or confluent pneumonitis infiltration were found, that was 7% of the whole study group. Clinical evidence of bleomycin-induced pneumonitis was found in 6 (15.4%) of 39 patients. With follow-up terms up to 60 months fibrotic changes in lungs were absent. The occurrence of radiation pneumonitis was 17.6%, radiation fibrosis – 35.9%. Fibrotic changes were mainly grade 1 (94.1%). In HL patients with bleomycin-induced pneumonitis the occurrence of radiation pneumonitis was 43.6% (17 of 39 patients), radiation fibrosis – 58.9% (23 of 39 patients) while the corresponding figures for patients who did not have bleomycin-induced pneumonitis were 8.7% (9 of 103 patients) and 27.2% (28 of 103 patients), respectively (p < 0.001).Conclusion. A statistically significant increase in occurrence of radiation pneumonitis and radiation fibrosis was defined in HL patients who suffered bleomycin-induced pneumonitis.

Long-Term Follow-Up of BEACOPPescalated Chemotherapy in Patients with Advanced-Stage Hodgkin Lymphoma on Behalf of the German Hodgkin Study Group.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 211-211
Author(s):  
Engert Andreas ◽  
Jeremy Franklin ◽  
Volker Diehl
Keyword(s):  
Hodgkin Lymphoma ◽  
Secondary Malignancy ◽  
Tumor Control ◽  
Study Group ◽  
Advanced Stage ◽  
Secondary Aml ◽  
German Hodgkin Study Group ◽  
Long Term Follow Up

Abstract The HD9 trial of the German Hodgkin Study Group (GHSG) compared two different doses (baseline and escalated) of the novel chemotherapy regimen BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in patients with advanced-stage Hodgkin lymphoma (HL). The previous analysis with a median follow-up of 5 years showed improved tumor control (FFTF) and overall survival (OS) for BEACOPPescalated. Since BEACOPPescalated had been associated with more toxicity as compared with ABVD we report the results of long-term follow-up of 1196 patients enrolled and randomized in that study. The median follow-up was 112 months; a total of 370 centres contributed. Patients received one of three chemotherapy regimens: 8 cycles of COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) alternating with ABVD (doxorubicin, bleomycin, vinblastin, and dacarbazine), 8 cycles of standard-dose BEACOPP or 8 cycles of escalated-dose BEACOPP. At 10 years, FFTF rates were 64%, 70% and 82%, OS rates were 75%, 80%, and 86 for COPP-ABVD (arm A), BEACOPPbaseline (arm B), and BEACOPPescalated, respectively (p &lt; 0,001). Importantly, BEACOPPescalated was also significantly better than BEACOPPbaseline in terms of FFTF (p &lt; 0.0001) and OS (p = 0.0053). Death due to HL occurred in 11.5%, 8.1% and 2.8% in arms A, B, and C, respectively. 74 second malignancies were documented, including secondary acute myeloid leukaemias (1,7,14), Non-Hodgkin lymphoma (7,8,5), and solid tumors (7,16,9) in arms A, B, and C respectively. The corresponding overall secondary malignancy rates were 6.7%, 8.9% and 6.8%. Importantly, the risk of secondary AML (sAML), although increased in this study after BEACOPPescalated, amounts to 0.9% in our follow-up study with BEACOPPescalated (HD12) in 1502 advanced-stage HL patients randomized and four years median follow-up. Although the higher rate of secondary AML after BEACOPPescalated in HD9 most likely occurred by chance, interestingly, 70% of patients in this group had additional radiotherapy whereas only 39% were radiated in HD12. Taken together, the 10 years follow-up of BEACOPPescalated chemotherapy demonstrates a stabilized significant improvement in long-term FFTF and OS for advanced-stage HL. Although for formal prove the results of ongoing prospective randomized comparisons with 8 cycles of ABVD might be required, these results clearly challenge ABVD as standard of care for this patient population.

High-Dose Cytoxan, Etoposide, and Cisplatin Followed by Autologous Hematopoietic Cell Transplantation for the Treatment of Hodgkin Lymphoma: A 20-Year Single-Institutional Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1913-1913
Author(s):  
Thomas R. Klumpp ◽  
Moshe C. Chasky ◽  
Robert V. Emmons ◽  
Mary E. Martin ◽  
James L. Gajewski ◽  
...  
Keyword(s):  
Complete Remission ◽  
Total Dose ◽  
Hodgkin Lymphoma ◽  
Pulmonary Toxicity ◽  
Median Number ◽  
High Dose ◽  
Post Transplant ◽  
Grade 3 ◽  
Active Disease

Abstract Since 1988 we have treated 66 patients with relapsed, refractory, or high-risk Hodgkin lymphoma (HD) with high-dose CEP consisting of cyclophosphamide 1,500 mg/m2/day × 4 (total dose, 6,000 mg/m2), etoposide 400 mg/m2 twice daily × 6 doses (total dose, 2,400 mg/m2), and cisplatin 50 mg/m2/day × 3 by continuous i.v. infusion (total dose 150 mg/m2) followed by infusion of autologous peripheral blood stem cells (n=49), bone marrow (n=16), or both (n=1). The patient population included 41 males and 25 females. The median age at transplant was 33 years (range, 17–64 years). Twenty-three patients (35%) had never achieved complete remission prior to transplant, 36 (55%) had previously achieved a complete remission but subsequently relapsed, and 3 (5%) were in first complete remission. Information regarding the disease status at transplant was unavailable for 4 patients (6%). Twenty-seven patients (41%) remain alive and free of any post-transplant relapse or progression as of the most recent follow-up, and an additional 10 patients (15%) manifested active disease post-transplant but are currently in remission following additional post-transplant therapy, yielding a total of 37 patients (56%) currently in CR. In addition, 5 patients (8%) remain alive with active disease, 23 patients (35%) died of progressive disease, and only 2 patients (3%) died of treatment-related causes including diffuse alveolar hemorrhage (1 patient) and hepatic veno-occlussive disease (1 patient). With a median follow-up of 4.4 years among surviving patients, the Kaplan-Meier 5-year estimates for event-free survival and overall survival are 34% and 60%, respectively, and five-year survival was superior among patients who had achieved at least one CR prior to transplant versus patients who had never been in CR prior to transplant (71% versus 43%, p = 0.03). Detailed adverse events data is available regarding all patients transplanted since September 1996: Of these, only 3 (7%) suffered grade 3 or greater pulmonary toxicity, 12 (29%) exhibited grade 3 or higher mucositis, and 10 (24%) had grade 3 or higher nausea or vomiting. The median number of days from transplant to neutrophil recovery (500 cells/uL) was 10 days, whereas the median number of days to platelet recovery (20,000 cells/uL) was 12 days. We conclude that high- dose CEP followed by autologous transplant is an active and well-tolerated treatment program in patients with relapsed or refractory HD. The low incidence of pulmonary toxicity is noteworthy given that a high percentage of patients had been exposed to bleomycin and/or thoracic XRT prior to transplant, and appears to be superior to that reported with conventional CBV-conditioned transplants in patients with HD.

Radiation Pneumonitis Risk after Bleomycin Toxicity in Hodgkin Lymphoma Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1511-1511
Author(s):  
Zeinab A Abou Yehia ◽  
George Mikhaeel ◽  
Grace Smith ◽  
Chelsea C Pinnix ◽  
Sarah A Milgrom ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Respiratory Symptoms ◽  
Cox Regression ◽  
Radiation Pneumonitis ◽  
Radiation Treatment ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
To Receive ◽  
Median Interval

Abstract Introduction: Combined modality treatment with Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) chemotherapy followed by consolidative radiation to start within 3-4 weeks is the current accepted approach in the treatment of patients with early stage Hodgkin lymphoma (HL). Bleomycin pulmonary toxicity (BPT) is a well-known complication of treatment in HL patients. We undertook this study to investigate the risk of radiation pneumonitis (RP) in the setting of BPT and to determine the need for delay or omission of radiation in these patients. Methods: We reviewed the records of all HL patients treated with ABVD followed by radiation therapy (RT) to the chest between January 2009 and December 2014. We defined bleomycin toxicity as: the occurrence of clinical respiratory symptoms leading to discontinuation of bleomycin and/or bilateral opacities noted on computed tomography (CT) imaging and/or drop in diffusing capacity of the lung for carbon monoxide (DLCO) by 25%, in the absence of infection. We identified 129 patients, 100 of which received consolidation RT as part of combined modality and are the subject of this report, 29 patients were excluded because they developed relapse before getting RT. We compared patients with and without bleomycin toxicity for the following outcomes:Frequency of RP using the Pearson chi-square test.Interval between BPT and Radiation using Mann-Whitney U test (MWT)Interval between end of chemotherapy and radiation using MWT. We used univariate Cox regression analysis to assess the risk of RP by looking at the time-interval in weeks from end of bleomycin to start of RT. Results: Median follow up was 23 months (6 - 69), Median age was 31 years (18-77), and 60% were females. Per our criteria, 28 patients developed BPT (25.5%). All patients received intensity modulated radiation therapy, radiation dose median was 30.60 Gy (20-42Gy). Mean lung dose (MLD) was a median of 9.4 Gy (2.6- 13.9 Gy). The median interval between chemotherapy and RT was 3 weeks (1- 8 weeks). Median interval from stopping bleomycin, either as a precaution or because of toxicity, to the start of RT was 5 weeks (1-20 weeks). Interval between documented bleomycin toxicity to start of radiation was a median of 8.5 weeks (2-20 weeks). We had 10 cases of RP (10%), 5 of which were ≥ Grade 2. There was no significant difference in RP risk in patients with or without BPT; 10.7% (3/28) versus 9.6% (7/72) respectively, P= 0.82. Patients with BPT versus those without BPT had no significant difference in baseline characteristics. The interval time from chemotherapy to radiation was a median of 3 weeks in both groups with or without BPT showing no difference; P= 0.83. However, Patients with BPT had a significantly longer interval from last bleomycin cycle to start of radiation compared to those without BPT (median 8.5 vs. 5 weeks, p =0.014). The intervals from chemotherapy to radiation treatment and from bleomycin to radiation treatment showed no significant correlation with RP on univariate Cox regression analysis (P= 0.41 and P= 0.12, respectively). This was maintained when adjusted for the number of bleomycin cycles. Treatment of BPT Of the 28 patients, 17 were managed by stopping bleomycin and observation only; 10 patients required a 2 week course of steroids. One patient went into severe respiratory compromise, was started on continuous oxygen and eventually recovered 48 hours later and went on to receive RT beginning 2 weeks after completing his steroid treatment. This patient did not have pulmonary complications after RT. All 28 BPT patients eventually completed their planned course of radiation. At last follow up, all 28 patients were alive and free of respiratory symptoms. Conclusion: In our cohort of Hodgkin lymphoma patients, those patients with bleomycin toxicity who received standard RT had no excess risk of subsequent RP. Moreover, patients were able to receive complete courses of RT to intended conventional radiation doses. Our findings suggest that RT does not need to be delayed following chemotherapy, except to allow for the completion of steroids or clinical recovery from BPT. Table 1. BPT_clinical BPT _imaging BPT_DLCO≥25% Clinical+(CTorDLCO≥25%) BPT per criteria All patients n=100 25 17 10 13 28 RP No n=90 22 15 9 12 25 Yes n=10 3 2 1 1 3 Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical and Radiographic Outcomes of Tibiotalocalcaneal or Pantalar Arthrodesis Using a Novel Lateral Locking Plate

2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0041
Author(s):  
Tyler Rutherford ◽  
John Campbell ◽  
Rebecca Cerrato ◽  
Clifford Jeng
Keyword(s):  
Plate Fixation ◽  
Large Diameter ◽  
Lateral Side ◽  
Study Group ◽  
X Rays ◽  
Lateral Plate ◽  
Side Plate ◽  
Tertiary Referral Center ◽  
Number Of Patients

Category: Ankle Introduction/Purpose: For patients suffering from severe ankle and hindfoot arthritis or deformity, tibiotalocalcaneal (TTC) or pantalar arthrodesis may be the best option to achieve a plantigrade and painless foot. These fusions are typically fixed with a retrograde intramedullary nail, a lateral side plate, or screws alone. Theoretically, the advantages of a lateral side plate applied via a trans-fibular approach include the use and the multiple points of fixation available in the tibia, talus, and calcaneus. The results of a novel side plate construct with a unique screw hole that extends underneath the calcaneus are presented in this study. A large diameter screw can be inserted retrograde through this inferior hole to engage the medial tibial cortex and provide axial compression across the ankle and subtalar joints. Methods: This study retrospectively evaluated 39 patients that underwent a tibiotalocalcaneal (TTC) or pantalar arthrodesis using this novel lateral plate fixation technique by one of three fellowship trained surgeons at a tertiary referral center. Patients with less than a one year follow up were excluded. Thirty-nine patients were identified between 2012 and 2016. Two patients were deceased from other causes, 2 had a below the knee amputation due to chronic pain, and 9 were lost to follow up. Pre- and postoperative General Health and Wellness (SF-12) and Revised Foot Function Index scores were obtained. Study subjects were seen for a clinical evaluation and final post-operative x-rays. The Shapiro-Wilk test was used to test for normality. The paired student’s t-test was used to compare pre- and post-surgical outcome measures. Results: Twenty-six patients were included in the study group. Mean follow up time was 34.42 ± 12.94 months. The SF-12 score was 32.2 ± 10.22 (physical) and 54.8 ± 10.7 (mental) before surgery, and 41.35 ± 9.21 (p < 0.01) and 56.5 ± 7.47 (p = 0.73) at final follow-up, respectively. The FFI score was 106 ± 32.69 before surgery and 53.94 ± 24.14 after surgery (p = 0.06). Eighteen patients were satisfied or very satisfied with the outcome of the surgery (70%). CT confirmation of joint fusion was obtained in all 26 patients. Twenty out of the 26 patients demonstrated fusion of all joints (77%). There were 2 ankle, 1 subtalar, and 1 talonavicular nonunions. In total, 44 of 48 total joints were fused (91%). Conclusion: Tibiotalocalcanceal and pantalar arthrodesis using a novel lateral plate for the treatment of complex deformity and severe osteoarthritis demonstrated acceptable fusion rates considering the number of patients with high risk factors for nonunion in this study group. Complications included fractures at the proximal end of the plate construct and persistent neurapraxia which was well tolerated. Patients reported significant improvements in SF-12 clinical scores at final 34 month follow-up.

Rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: long-term follow-up of a phase 2 study from the German Hodgkin Study Group

Leukemia ◽  
2019 ◽  
Vol 34 (3) ◽  
pp. 953-956 ◽  
Author(s):  
Dennis A. Eichenauer ◽  
Annette Plütschow ◽  
Michael Fuchs ◽  
Sylvia Hartmann ◽  
Martin-Leo Hansmann ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Study Group ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
German Hodgkin Study Group ◽  
Phase 2 Study ◽  
Long Term Follow Up ◽  
Stage Ia

Long-Term Follow-Up of Contemporary Treatment in Early-Stage Hodgkin Lymphoma: Updated Analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 Trials

2017 ◽  
Vol 35 (18) ◽  
pp. 1999-2007 ◽  
Author(s):  
Stephanie Sasse ◽  
Paul J. Bröckelmann ◽  
Helen Goergen ◽  
Annette Plütschow ◽  
Horst Müller ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Therapeutic Strategies ◽  
Combined Modality Treatment ◽  
Study Group ◽  
Long Term Follow Up ◽  
Extended Field ◽  
Involved Field

Purpose Combined-modality treatment is widely considered the standard of care in early-stage Hodgkin lymphoma (HL), and treatment intensity has been reduced over the last years. Long-term follow-up is important to judge both efficacy and safety of the different therapies used. Patients and Methods We analyzed updated follow-up data on 4,276 patients treated within the German Hodgkin Study Group trials HD7 and HD10 for early-stage favorable HL and HD8 and HD11 for early-stage unfavorable HL between 1993 and 2003. Results In HD7 (N = 627; median follow-up, 120 months), combined-modality treatment was superior to extended-field radiotherapy (RT), with 15-year progression-free survival (PFS) of 73% versus 52% (hazard ratio [HR], 0.5; 95% CI, 0.3 to 0.6; P < .001), without differences in overall survival (OS). In HD10 (N = 1,190; median follow-up, 98 months), noninferiority of two cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) plus 20 Gy involved-field (IF)–RT to more intensive four cycles of ABVD plus 30 Gy IF-RT was confirmed with 10-year PFS of 87% each (HR, 1.0; 95%, 0.6 to 1.5) and OS of 94% each (HR, 0.9; 95% CI, 0.5 to 1.6), respectively. In both trials, no differences in second neoplasias were observed. In HD8 (N = 1,064; median follow-up, 153 months), noninferiority of involved-field RT to extended-field RT regarding PFS was confirmed (HR, 1.0; 95% CI, 0.8 to 1.2). In HD11 (N = 1,395; median follow-up, 106 months), superiority of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone at baseline over ABVD was not observed. After BEACOPPbaseline, 20 Gy IF-RT was noninferior to 30 Gy (10-year PFS, 84% v 84%; HR, 1.0; 95% CI, 0.7 to 1.5). In contrast, PFS was inferior in ABVD-treated patients receiving 20 Gy instead of 30 Gy IF-RT (10-year PFS, 76% v 84%; HR, 1.5; 95% CI, 1.0 to 2.1). No differences in OS or second neoplasias were observed in in both trials. Conclusion Long-term follow-up data of the four randomized trials largely support the current risk-adapted therapeutic strategies in early-stage HL. Nevertheless, continued follow-up is necessary to assess the long-term safety of currently applied therapeutic strategies.

Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG)

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 109-111 ◽  
Author(s):  
Holger Schulz ◽  
Ute Rehwald ◽  
Franck Morschhauser ◽  
Thomas Elter ◽  
Christoph Driessen ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
B Cell Lymphoma ◽  
Long Term Results ◽  
Study Group ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Reference Pathology ◽  
Lymphoma Study Group

Because nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) express CD20, rituximab may be used as a nonmutagenic treatment option to avoid late toxicities in this rather indolent entity. Between 1999 and 2004, the German Hodgkin Study Group (GHSG) investigated the activity of rituximab (375 mg/m2 in 4 doses) in a phase 2 trial in 21 relapsed or refractory NLPHL patients. The initial diagnosis of NLPHL was confirmed in 15 of the 21 enrolled patients by reference pathology. The remaining cases were reclassified as Hodgkin lymphoma transformed to T-cell rich B-cell lymphoma (TCRBCL; n = 2) or CD20+ classical Hodgkin lymphoma (cHL; n = 4). In NLPHL patients the overall response rate was 94%, including 8 complete remission (CR) and 6 partial remission (PR). With a median follow-up of 63 months (range, 3-84), the median time to progression was 33 months, with the median overall survival (OS) not reached. Thus, rituximab is highly effective in relapsed and refractory NLPHL. This study is registered at http://www.klinisches-studienzentrum.de/trial/285.

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