Comorbidity assessment to determine prognosis in older adult patients with classical Hodgkin lymphoma

The clinical management of older adult patients with Hodgkin lymphoma (HL) remains a major challenge. The aim of this study was to evaluate the impact of comorbidity assessment according to a standardized approach, the Cumulative Illness Rating Scale (CIRS), on prognosis in patients with classical HL aged 60 years and older. We studied 76 consecutive older adult patients with HL (median age 69 y, range 60-84) who had been treated in our institution between 1999 and 2018. Comorbidity was assessed at diagnosis according to CIRS. Anthracycline-containing chemotherapy with curative intent was administered in 59 (78%) patients. We identified 41 (54%) patients with at least one severe comorbidity rated on CIRS grade ≥ 3. Patients with severe comorbidity were more likely to have advanced-stage disease (P = .003), to have an International Prognostic Score (IPS) > 3 (P = .03), and to not receive anthracycline-containing chemotherapy (P = .008). The probability of overall survival (OS) at 3 years was 88% (95% CI, 71%-95%) in patients without severe comorbidities, while it was only 46% (95% CI, 29%-62%) in patients with a comorbidity CIRS grade ≥ 3 (P = .0001). The impact of comorbidity on prognosis was also evident when restricting the analysis to patients treated with anthracycline-containing therapy. The 3-year OS was 93% (95% CI, 76%-98%) (P = .004) in patients without severe comorbidity and 72% (95% CI, 47%-87%) in patients with severe comorbidity (P = .004). In a multivariate analysis, presence of comorbidity, but not age, was a significant factor for OS. Therefore, we conclude that a significant proportion of older adult patients with HL has severe comorbidity on the CIRS scale, which impacts more importantly than age on prognosis.     

Initial response to salvage therapy determines prognosis in relapsed pediatric Hodgkin lymphoma patients

BACKGROUND:

Pediatric Hodgkin lymphoma (HL) is a highly curable disease; however, prognostic factors for the survival of patients who develop recurrent disease have not been clearly defined.

METHODS:

This was a retrospective analysis of 50 pediatric patients with HL who relapsed or progressed between 1990 and 2006 and who were retrieved with intense cytoreductive treatment regimens followed by autologous stem cell transplantation and radiation therapy. A Cox proportional hazards model was used to determine risk factors for second treatment failure and death.

RESULTS:

The median patient age was 16.1 years (range, 4.9‐22.1 years) at the time of HL diagnosis. Fifteen patients developed progressive disease during therapy, 14 patients relapsed early, and 21 patients relapsed late. Patients who remained alive at the time of this study had been followed for a median of 4.4 years (range, 1.2‐16.6 years). The 5‐year overall survival rate for patients who had an inadequate response (n = 14) to initial salvage therapy was only 17.9% (95% confidence interval [CI], 3.1%‐42.5%) compared with 97.2% (95% CI, 81.9%‐99.6%) for patients who responded (n = 36; P < .0001). In a multivariate Cox regression analysis of overall survival, an inadequate response to initial salvage therapy was the only significant variable (hazard ratio, 43.6; 95% CI, 5.4‐354; P = .0004).

CONCLUSIONS:

The current results indicated that pediatric patients with relapsed HL who have an inadequate response after initial primary salvage chemotherapy have a very poor prognosis and should be considered for novel therapies directed at biologic or immunologic targets. Cancer 2010. © 2010 American Cancer Society.     

A Chinese patient with relapsed and refractory Hodgkin lymphoma treated with brentuximab vedotin

At present,approximately 20%of Hodgkin lymphomas(HL)are relapsed and refractory,and therapeutic methods including chemotherapy,radiotherapy,and even stem cell transplantation are unsatisfactory.Brentuximab vedotin,composed of CD30 antibody and a chemotherapeutic agent,is a new targeted drug that eradicates tumor cells by binding to the CD30 antigen on their surface.In clinical trials,the response rate and complete remission rate of this drug were 73%and 40%,respectively,for relapsed and refractory HL.Here we report a case of CD30-positive relapsed and refractory HL that was treated with brentuximab.Before the treatment with brentuximab,the patient underwent chemotherapy,radiotherapy,and autologous stem cell transplantation.However,the disease continued to progress,affecting multiple organs and prompting symptoms such as persistent fever.After the treatment with brentuximab,the patient′s condition improved.Body temperature returned to normal after 4 days.Lung nodules were reduced in size and number after a single course of treatment,and PET/CT showed partial remission and complete remission after 3 and 6 courses of treatment,respectively.The entire treatment process progressed smoothly,though the patient experienced some symptoms due to chemotherapy,including peripheral neuritis of the limbs,irritating dry cough,and mild increase in aminotransferase.No serious adverse effects were observed.The current general condition of the patient is good;the continuous complete remission has amounted to 6 months.     

Suppressor of cytokine signaling 1 gene mutation status as a prognostic biomarker in classical Hodgkin lymphoma

Suppressor of cytokine signaling 1 (SOCS1) mutations are among the most frequent somatic mutations in classical Hodgkin lymphoma (cHL), yet their prognostic relevance in cHL is unexplored. Here, we performed laser-capture microdissection of Hodgkin/Reed-Sternberg (HRS) cells from tumor samples in a cohort of 105 cHL patients. Full-length SOCS1 gene sequencing showed mutations in 61% of all cases (n = 64/105). Affected DNA-motifs and mutation pattern suggest that many of these SOCS1 mutations are the result of aberrant somatic hypermutation and we confirmed expression of mutant alleles at the RNA level. Contingency analysis showed no significant differences of patient-characteristics with HRS-cells containing mutant vs. wild-type SOCS1. By predicted mutational consequence, mutations can be separated into those with non-truncating point mutations (‘minor’ n = 49/64 = 77%) and those with length alteration (‘major’; n = 15/64 = 23%). Subgroups did not differ in clinicopathological characteristics; however, patients with HRS-cells that contained SOCS1 major mutations suffered from early relapse and significantly shorter overall survival (P = 0.03). The SOCS1 major status retained prognostic significance in uni-(P = 0.016) and multivariate analyses (P = 0.005). Together, our data indicate that the SOCS1 mutation type qualifies as a single-gene prognostic biomarker in cHL.     

Phase 2 study of gemcitabine in combination with rituximab in patients with recurrent or refractory Hodgkin lymphoma

BACKGROUND: The management of recurrent or refractory Hodgkin lymphoma (HL) remains challenging. The objective of this phase 2 trial was to investigate the activity of gemcitabine in combination with rituximab in patients with recurring or refractory HL. METHODS: Patients were considered eligible if they had recurring or refractory HL, had received >or=2 prior chemotherapy regimens, had an Eastern Cooperative Oncology Group (ECOG) performance status 相似文献   

Twenty-year disease and treatment-associated mortality rates of patients with Hodgkin lymphoma of clinical stages IIIB and IV prospectively treated with 3-month anthracycline-based chemotherapy followed by extended high-dose radiation

BACKGROUND: In 1981, the authors developed an original strategy combining 3 cycles of doxorubicin (adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) or ABVD-like chemotherapy and extended high-dose radiation for treating patients with clinical stages IIIB and IV Hodgkin lymphoma (HL). In the current study, the authors analyzed the 20-year results of this treatment as applied to 213 patients according to 2 successive trials. METHODS: All patients who responded to chemotherapy received extended high-dose radiation. The rates of complete remission (CR), freedom from disease progression (FFP), HL-specific survival (HLSS), second tumors and cardiac events, freedom from treatment-associated mortality (FFTM), overall survival (OS), and event-free survival were calculated. RESULTS: In December 2006, the median follow-up of the surviving patients exceeded 13 years; 102 patients (48%) achieved a CR after chemotherapy and 178 patients (84%) did so after radiotherapy. The rates of FFP (61%, quasi-stable after 6 years) and HLSS (81.6%, stable after 12 years) were found to be significantly higher in patients who achieved a CR after chemotherapy. The incidence of hematologic malignancies was 10.9% (with 10 of 12 events occurring within the first 7 years). The rates of solid tumors (32.4%), cardiac events (33.4%), and FFTM (65.6%) did not reach any plateau by 20 years and were found to be significantly associated with patient age. The 20-year OS rate was 48%. CONCLUSIONS: This combined modality treatment gave long-term results similar to those obtained using 6 to 8 cycles of ABVD. Response to the initial brief chemotherapy administration was found to be predictive of the FFP and HLSS rates. The low rate of FFTM was the result of extended high-dose radiation. The results of the current study should help to design future trials for treating patients with advanced stages of HL.     

Pretransplantation [18‐F]fluorodeoxyglucose positron emission tomography scan predicts outcome in patients with recurrent Hodgkin lymphoma or aggressive non‐Hodgkin lymphoma undergoing reduced‐intensity conditioning followed by allogeneic stem cell transplantation

BACKGROUND:

The use of positron emission tomography (PET) scanning in Hodgkin lymphoma (HL) and aggressive non‐Hodgkin lymphoma (HG‐NHL) has recognized prognostic value in patients who are receiving chemotherapy or undergoing autologous stem cell transplantation (SCT). In contrast, the role of PET before reduced‐intensity conditioning (RIC) and followed by allogeneic SCT has not been investigated to date.

METHODS:

PET was used to assess 80 patients who had chemosensitive disease (34 patients with HG‐NHL and 46 patients with HL) before they underwent allogeneic SCT: 42 patients had negative PET studies, and 38 patients had positive PET studies. Patients underwent allograft from matched related siblings (n = 41) or alternative donors (n = 39).

RESULTS:

At the time of the last follow‐up, 48 patients were alive (60%), and 32 had died. The 3‐year cumulative incidence of nonrecurrence mortality and disease recurrence was 17% and 40%, respectively. The cumulative incidence of disease recurrence was significantly lower in the PET‐negative patients (25% vs 56%; P = .007), but there was no significant difference between the patients with or without chronic graft‐versus‐host disease (P = .400). The patients who had negative PET studies before undergoing allogenic SCT also had significantly better outcomes in terms of 3‐year overall survival (76% vs 33%; P = .001) and 3‐year progression‐free survival (73% vs 31%; P = .001). On multivariate analysis, overall survival was influenced by PET status (hazard ratio [HR], 3.35), performance status (HR, 5.15), and type of donor (HR, 6.26 for haploidentical vs sibling; HR, 1.94 for matched unrelated donor vs sibling).

CONCLUSIONS:

The current results indicated that PET scanning appears to be an accurate tool for assessing prognosis in patients who are eligible for RIC allografting. Cancer 2010. © 2010 American Cancer Society.     

晚期经典型霍奇金淋巴瘤的治疗进展

晚期经典型霍奇金淋巴瘤的治疗在过去的50年间有了很大的进步,带来了治愈率的提高.不过,患者大都经历了高强度化疗相关的严重并发症.在一线治疗中组合应用"根据疾病危险分层调整治疗策略"和"根据对初始治疗反应调整策略"可能是一个很好的选择.新药如BV和免疫检查点抑制剂使很多复发难治的霍奇金淋巴瘤患者获得了收益.自体造血干细胞...     

Association between insurance and socioeconomic status and risk of advanced stage Hodgkin lymphoma in adolescents and young adults

BACKGROUND:

Hodgkin lymphoma (HL) is one of the most common types of cancer among adolescents and young adults (AYAs) in the United States. Unfortunately, a greater percentage of AYAs are presenting with an advanced stage of disease at the time of diagnosis compared with their younger counterparts.

METHODS:

The objective of the current study was to examine the association between possible barriers and characteristics (including gender, race, birthplace, marital status, socioeconomic status [SES], and insurance status) that may increase the risk of advanced stage HL at the time of diagnosis in a large cohort of AYA patients with HL from the California Cancer Registry (7343 incident cases of HL diagnosed from 1988‐2006, between ages 15 years‐40 years).

RESULTS:

AYAs with advanced stage HL were more likely to be male, of Hispanic or black race/ethnicity, foreign born, single, of lower SES, and uninsured or to have only public health insurance (P < .05). Multivariate logistic regression analysis demonstrated that there was a significant increase in the odds of having advanced HL in males (odds ratio [OR], 1.57; 95% confidence interval [95% CI], 1.42‐1.74 [P < .0001]), those with the lowest SES (OR, 1.47; 95% CI, 1.23‐1.75 [P = .0003]), those without health insurance (OR, 1.76; 95% CI, 1.34‐2.31 [P < .0001]), and those with public health insurance (OR, 1.45; 95% CI, 1.23‐1.71 [P < .0001]).

CONCLUSIONS:

A strong association was found between male gender, lower SES, and lack of health insurance and advanced stage HL at the time of diagnosis in AYAs (See editorial on pages 000–000, this issue.) Cancer 2012. © 2012 American Cancer Society.     

Resection alone in 58 children with limited stage, lymphocyte-predominant Hodgkin lymphoma-experience from the European network group on pediatric Hodgkin lymphoma

BACKGROUND: Lymphocyte-predominant Hodgkin lymphoma (LPHL) is a rare, CD20-positive, good prognostic lymphoma in children. Patients with early-stage LPHL who underwent successful surgical lymph node resection alone have been reported. To clarify the optimum treatment strategy in children, European study groups were asked to report their experience of surgery alone used in the treatment of pediatric LPHL. METHODS: Data from 58 patients were collected by the French Society for Pediatric Cancers, the German-Austrian Pediatric Study Group/German Society of Pediatric Oncology and Hematology (Germany), and the Children's Cancer and Leukaemia Group (United Kingdom). In total, there were 50 boys and 8 girls, and the median age was 11 years (age range, 4-17 years). Fifty-four patients had stage IA disease, 2 patients had stage IIA disease, and 2 patients had stage IIIA disease. RESULTS: With a median follow-up of 43 months (range, 2-202 months), the overall survival rate was 100%, and the progression-free survival (PFS) rate was 57%. Fifty-one of 58 patients achieved complete remission (CR) after surgery. In the CR group, the overall PFS rate was 67% (95% confidence interval, 51-82%). All seven patients who had residual disease after initial surgery developed recurrences (P = .003). Among 18 patients with stage IA LPHL who developed recurrent disease, 11 patients had local recurrences, and 7 patients recurred in stage IIA. One patient with stage IIIA disease presented with high-grade B-cell non-Hodgkin lymphoma at 10 years of follow-up. CONCLUSIONS: When complete resection was achieved, a substantial proportion of patients with surgically treated, early-stage LPHL experienced long-term remission and actually may have been cured.     

预后好的早期霍奇金淋巴瘤的综合治疗

目的 探讨预后好的早期霍奇金淋巴瘤(HL)的治疗方法,分析其预后因素.方法 对137例预后好的早期HL进行回顾性分析,其中84例(61.3%)接受单纯放疗,53例(38.7%)接受联合放化疗.研究指标包括近期疗效,5年、10年总生存(OS)率,无瘤生存(DFS)率,复发和死亡原因.结果 单纯放疗组和联合化放组的完全缓解(CR)率分别为71.4%和86.8%(x2=4.381,P=0.036),5年、10年OS率分别为84.4%、78.2%和81.1%、81.1%(P=0.556),5年、10年DFS率分别为85.4%、66.7%和94.1%、94.1%(P=0.047).全组22例复发,中位复发时间为16.5个月;23例(16.8%)死亡,其中9例(39.1%)死于HL.结论与单纯放疗相比,联合化放疗能提高预后好的早期HL的CR率和DFS率,但不提高OS率.     

Treatment outcomes and relative dose intensity of chemotherapy in patients with advanced Hodgkin lymphoma

The present retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of patients with advanced stage Hodgkin lymphoma (HL) receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimens (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 patients with HL treated between 2004 and 2013 were enrolled for evaluation. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, and the majority were male and had stage IV disease. A total of 54 patients received ABVD and 60 received BEACOPP chemotherapy with 24 and four deaths, respectively. Patients in the BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) and better performance status in comparison with the ABVD group, making the comparison of groups not possible. In the ABVD group, RDI was not significantly associated with OS (P=0.590) or PFS (P=0.354) in a multivariate model where age was controlled. The low number of events prevented this analysis in the BEACOPP group. The age of patients was strongly associated with both OS and PFS; all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI, performance status) lost their effect in multivariate analyses where age was controlled. Based on these observations, it was concluded that RDI was not associated with OS or PFS after age is controlled, neither in all patients combined nor in the ABVD group.     

非霍奇金淋巴瘤血清VEGF水平与疗效及预后的相关性研究

目的 研究非霍奇金淋巴瘤（NHL）患者血管内皮生长因子（VEGF）的表达及其与化疗疗效和预后的相关性,探讨VEGF作为NHL疗效预测和预后评估标志物的可能性.方法 采用酶联免疫吸附技术检测60例NHL患者治疗前后血清VEGF水平,并观察VEGF水平与疗效和生存的关系,同时检测20例正常对照者血清VEGF水平.结果 NHL患者血清VEGF为（338.64±259.31） pg/ml,明显高于正常对照者的（72.57±26.16） pg/ml（t=7.829,P=0.000）.NHL患者血清VEGF水平与国际预后指数（IPI）及结外侵犯相关（t=-3.747,P=0.002;t=-3.000,P=0.005）,而与年龄、性别、分期、美国东部肿瘤协作组体力状态（ECOG PS）评分无明显相关性.治疗后部分和完全缓解（PR和CR）患者血清VEGF水平较治疗前明显降低（t=2.729,P=0.010）.血清VEGF水平与患者生存期无明显相关性（t=-0.563,P=0.577）.结论 初治NHL患者血清VEGF水平高于正常对照者,尤其与IPI和结外侵犯数量相关;血清VEGF水平变化与化疗疗效相关,但与生存期无明显相关性.     

Surveillance imaging of Hodgkin lymphoma patients in first remission

BACKGROUND:

The majority of patients with Hodgkin lymphoma (HL) achieve disease remission after primary therapy. To the best of the authors' knowledge, no consensus exists for postremission surveillance imaging.

METHODS:

Retrospectively analyzed were 192 adult patients with classic HL in first remission. Events were defined as recurrent HL or secondary malignancies. Primary outcome was positive predictive value (PPV) of surveillance positron emission tomography/computed tomography (PET/CT) and CT scans in event detection. Secondary outcomes were costs and radiation exposures of surveillance scans.

RESULTS:

Sixteen events (12 recurrent HL cases and 4 secondary malignancies) were detected during a median follow‐up of 31 months. The PPV of surveillance PET/CT was 22.9% compared with 28.6% for CT (P = .73). Factors that were found to significantly improve the PPV of scans in detecting recurrent HL included PET and CT concordance, involvement of a prior disease site, or the occurrence of a radiographic abnormality within 12 months. There were too few events to determine whether event detection by PET/CT versus CT or the presence of symptoms at the time of event detection affected overall outcomes. The cost to detect a single event was approximately $100,000. Radiation exposure to detect a single event was 146.6 millisieverts per patient for each of 9 patients.

CONCLUSIONS:

For patients with HL in first disease remission, surveillance radiography appears to be expensive, with limited clinical impact. Surveillance CT is generally adequate. Cancer 2010. © 2010 American Cancer Society.