The homeobox (HOX) genes are a highly conserved family of homeodomain-containing transcription factors that specify cell identity in early development and, subsequently, in a number of adult ...processes including hematopoiesis. The dysregulation of HOX genes is associated with a number of malignancies including acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), where they have been shown to support the immortalization of leukemic cells both as chimeric partners in fusion genes and when overexpressed in their wild-type form. This review covers our current understanding of the role of HOX genes in normal hematopoiesis, AML and ALL, with particular emphasis on the similarities and differences of HOX function in these contexts, their hematopoietic downstream gene targets and implications for therapy.
Purpose
Lymphoma survivors experience persisting needs as a consequence of disease and treatment, which have an impact on quality of life (QoL). There is evidence supporting the use of relaxation and ...exercise to improve QoL, but there is no agreement on which is more beneficial. This study aims to compare a relaxation intervention versus an exercise intervention to determine which has a greater impact on QoL post-chemotherapy.
Methods
Eligible participants (
n
= 46) were randomised to a relaxation or exercise intervention for 12 weeks. QoL was assessed at baseline, 6 weeks and post-intervention using the European Organisation for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30) questionnaire, which is a valid and reliable tool. The summary score and all EORTC domains were assessed.
Results
There was a significant difference in QoL post-intervention between groups (
p
= 0.029) while adjusting for baseline QoL, with the exercise group demonstrating a larger improvement. Within-group QoL significantly improved pre- to post-intervention in both the relaxation (
p
= 0.036) and exercise (
p
= 0.004) groups.
Conclusions
A self-management intervention of either exercise or relaxation can help significantly improve QoL in lymphoma survivors following chemotherapy. While exercise is preferred, a relaxation intervention would also have a beneficial impact on QoL.
Implications for Cancer Survivors
Lymphoma survivors should be routinely screened and those with decreased QoL referred for an exercise programme, or relaxation for survivors who are unable to exercise or choose not to. A home-based programme can have a significant positive impact on QoL and is a feasible and effective method in the current climate.
Trial registration number
Clinical Trials ID NCT02272751
Abstract Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing ...severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival. In Europe, prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. The need for generally applicable, European-focused guidelines led to the formation of a European Guidelines Working Party by the European Organisation for Research and Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new systematic literature review has been undertaken to ensure that recommendations are current and provide guidance on clinical practice in Europe. We recommend that patient-related adverse risk factors, such as elderly age (⩾65 years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy. It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles. We provide an expanded list of common chemotherapy regimens considered to have a high (⩾20%) or intermediate (10–20%) risk of FN. Prophylactic G-CSF continues to be recommended in patients receiving a chemotherapy regimen with high risk of FN. When using a chemotherapy regimen associated with FN in 10–20% of patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Clinical evidence shows that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications where indicated. Filgrastim biosimilars are also approved for use in Europe. While other forms of G-CSF, including biosimilars, are administered by a course of daily injections, pegfilgrastim allows once-per-cycle administration. Choice of formulation remains a matter for individual clinical judgement. Evidence from multiple low level studies derived from audit data and clinical practice suggests that some patients receive suboptimal daily G-CSFs; the use of pegfilgrastim may avoid this problem.
Purpose
Further research on patient experience and involvement is recommended in order to develop evidence-based and meaningful care pathways for lymphoma survivors. This study aims to explore the ...experience of a sample of lymphoma survivors participating in a home-based intervention following chemotherapy.
Methods
Eligible participants who completed a 12-week home-based intervention were invited to complete the End of Study Questionnaire designed to explore perceptions, preferences and barriers to participation. Content analysis was used to generate codes, describe frequencies and identify themes.
Results
Participating in a home-based intervention post-treatment was a positive experience overall, and aided recovery in this sample of lymphoma survivors (
n
= 35). Participants felt the programme provided structure, motivation and liked contact with the researcher. Participants highlighted their need for advice on healthy lifestyle, diet in particular.
Conclusions
Lymphoma survivors in this study reported participation in a home-based intervention following treatment beneficial and aided recovery.
Implications for cancer survivors
A large proportion of lymphoma survivors would benefit from a rehabilitation intervention post-chemotherapy. Intervention programmes should include follow-ups to monitor progress and provide support and motivation. Health professionals should recommend healthy lifestyle guidelines to survivors on completion of treatment or refer patients to appropriate services for rehabilitation and advice.
Outcomes for patients with high-risk diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP chemotherapy are suboptimal but, to date, no alternative regimen has been shown to improve survival ...rates. This phase 2 trial aimed to assess the efficacy of a Burkitt-like approach for high-risk DLBCL using the dose-intense R-CODOX-M/R-IVAC regimen.
Eligible patients were aged 18–65 years with stage II–IV untreated DLBCL and an International Prognostic Index (IPI) score of 3–5. Patients received alternating cycles of CODOX-M (cyclophosphamide, vincristine, doxorubicin and high-dose methotrexate) alternating with IVAC chemotherapy (ifosfamide, etoposide and high-dose cytarabine) plus eight doses of rituximab. Response was assessed by computed tomography after completing all four cycles of chemotherapy. The primary end point was 2-year progression-free survival (PFS).
A total of 111 eligible patients were registered; median age was 50 years, IPI score was 3 (60.4%) or 4/5 (39.6%), 54% had a performance status ≥2 and 9% had central nervous system involvement. A total of 85 patients (76.6%) completed all four cycles of chemotherapy. There were five treatment-related deaths (4.3%), all in patients with performance status of 3 and aged >50 years. Two-year PFS for the whole cohort was 67.9% 90% confidence interval (CI) 59.9–74.6 and 2-year overall survival was 76.0% (90% CI 68.5–82.0). The ability to tolerate and complete treatment was lower in patients with performance status ≥2 who were aged >50 years, where 2-year PFS was 43.5% (90% CI 27.9–58.0).
This trial demonstrates that R-CODOX-M/R-IVAC is a feasible and effective regimen for the treatment of younger and/or fit patients with high-risk DLBCL. These encouraging survival rates demonstrate that this regimen warrants further investigation against standard of care.
ClinicalTrials.gov (NCT00974792) and EudraCT (2005-003479-19).
•R-CODOX-M/R-IVAC is an effective regimen for treatment of high-risk DLBCL and high-grade B-cell lymphoma (IPI score 3–5).•Treatment was well tolerated in patients aged <50 years, or aged 50–65 with performance status 0 or 1.•The 2-year PFS was 67.9% (90% CI: 59.9–74.6) for the whole cohort.•This regimen warrants further evaluation against standard of care in high-risk DLBCL.
The aim of this subgroup analysis of the Mabthera International Trial Group study was to evaluate the impact of chemotherapy and rituximab in primary mediastinal B-cell lymphoma (PMBCL) in comparison ...to other diffuse large B-cell lymphoma (DLBCL).
Patients were randomly assigned to six cycles of CHOP-like regimens with or without rituximab.
Of 824 patients enrolled, 87 had PMBCL and 627 other types of DLBCL. Rituximab increased the rates of complete remission (unconfirmed) in both PMBCL (from 54% to 80%, P = 0.015) and DLBCL (from 72% to 87%, P < 0.001). In PMBCL, rituximab virtually eliminated progressive disease (PD) (2.5% versus 24%, P < 0.001), whereas without rituximab, PD was more frequent in PMBCL than in DLBCL (24% versus 10%, P = 0.010). With a median observation time of 34 months, 3-year event-free survival (EFS) was improved by rituximab for PMBCL (78% versus 52%, P = 0.012) and for DLBCL (81% versus 61%, P < 0.001). Overall survival benefit was similar for DLBCL (93% versus 85%, P < 0.001) and PMBCL (89% versus 78%, P = 0.158).
In young patients with PMBCL (age-adjusted International Prognostic Index 0–1), rituximab added to six cycles of CHOP-like chemotherapy increases response rate and EFS to the same extent as other DLBCL. The combination of rituximab with CHOP chemotherapy is an effective treatment in PMBCL with good prognosis features.
Chemotherapy-induced neutropenia is not only a major risk factor for infection-related morbidity and mortality, but is also a significant dose-limiting toxicity in cancer treatment. Patients ...developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact on the success of treatment, particularly when treatment intent is either curative or to prolong survival. The incidence of severe or FN can be reduced by prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim, lenograstim or pegfilgrastim. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. While several academic groups have produced evidence-based clinical practice guidelines in an effort to standardise and optimise the management of FN, there remains a need for generally applicable, European-focused guidelines. To this end, we undertook a systematic literature review and formulated recommendations for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. We recommend that patient-related adverse risk factors such as elderly age (⩾65 years), be evaluated in the overall assessment of FN risk prior to administering each cycle of chemotherapy. In addition, when using a chemotherapy regimen associated with FN in >20% patients, prophylactic G-CSF is recommended. When using a chemotherapy regimen associated with FN in 10–20% patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Finally, studies have shown that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications, where indicated.
We report the 12-year follow-up of the prospective randomized EBMT LYM1 trial to determine whether the benefit of brief duration rituximab maintenance (RM) on progression-free survival (PFS) in ...patients with relapsed follicular lymphoma (FL) receiving an autologous stem cell transplant (ASCT) is sustained. One hundred and thirty-eight patients received RM with or without purging. The median follow-up after random assignment is 12 years (range 10-13) for the whole series. The 10-year PFS after ASCT is 47% (95% CI 40-54) with only 4 patients relapsing after 7.5 years. RM continues to significantly improve 10-year PFS after ASCT in comparison with NM P = 0.002; HR 0.548 (95% CI 0.38-0.80). Ten-year non-relapse mortality (NRM) was not significantly different between treatment groups (7% overall). 10-year overall survival (OS) after ASCT was 75% (69-81) for the whole series, with no significant differences according to treatment sub-groups. 10-year OS for patients who progressed within 24 months (POD24T) was 60%, in comparison with 85% for patients without progression. Thus the benefit of rituximab maintenance after ASCT on relapse prevention is sustained at 12 years, suggesting that RM adds to ASCT-mediated disease eradication and may enhance the curative potential of ASCT.
This study compares outcome of reduced-intensity conditioned transplant (RIT) with outcome of conventional non-transplant therapy in patients with Hodgkin's lymphoma relapsing following autograft. ...There were 72 patients in two groups who had relapsed, and received salvage therapy with chemotherapy+/-radiotherapy. One group (n=38) then underwent alemtuzumab-containing RIT. The second group-historical controls (n=34), relapsing before the advent of RIT-had no further high-dose therapy. This group was required to respond to salvage therapy and live for over 12 months post-relapse, demonstrating potential eligibility for RIT, had this been available. Overall survival (OS) from diagnosis was superior following RIT (48% at 10 years versus 15%; P=0.0014), as was survival from autograft (65% at 5 years versus 15%; P< or =0.0001). For the RIT group, OS at 5 years from allograft was 51%, and in chemoresponsive patients was 58%, with current progression-free survival of 42%. Responses were seen in 8 of 15 patients receiving donor lymphocyte infusions (DLI) for relapse/progression, with durable remission in five patients at median follow-up from DLI of 45 months (28-55). These data demonstrate the potential efficacy of RIT in heavily pre-treated patients whose outlook with conventional therapy is dismal, and provide evidence of a clinically relevant graft-versus-lymphoma effect.
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