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Hodgkin Lymphoma (HL)
Haematological Pathway
for
South Wales Cancer Network
Document Control Sheet
OrganisationSouth Wales Cancer NetworkSpecialty/ProjectHaematological Site Specific GroupDocument TitleHodgkin Lymphoma (HL)Document Number05/016
VersionAuthor/sRatified by1.0Dr Eve Gallop-EvansDr W IngramApproved byApproval dateDate of next reviewSouth Wales Haematology Cancer Network Group17/09/1416/09/15
NSAG Hodgkin Lymphoma Patient Care Pathway
Diagnosis
An excision biopsy is recommended in preference to a core biopsy to ensure adequate tissue for diagnosis.
AWLP confirmation required for diagnosis of:
Classical HL
Nodular lymphocyte predominant HL
All cases should be discussed at a Lymphoma MDT meeting:
At diagnosis and on completion of staging, to confirm management plan and discuss any relevant clinical trials.
At time of response assessment, during and at the end of treatment, to decide on appropriate management.
All patients aged from 15-24 should be referred to the appropriate TYA team and discussed at the TYA MDT.
Patients under the age of 18 must receive care in the principal treatment centre offering age-appropriate facilities and access to the TYA MDT. Patients aged 19 to 24 yrs should be referred to the TYA MDT for support, and should also be offered the choice of being treated at the PTC or locally.
Staging, clinical & prognostic markers and pre-treatment investigations
Documentation of stage, systemic symptoms, International Prognostic Score, co-morbidities.
FBC, ESR, renal, liver & bone profile, LDH, viral screen (HIV, hepatitis B and C).
Contrast-enhanced CT scan of neck, thorax, abdomen, pelvis,
Staging PET-CT scan (if contrast given for this, can omit separate CT).
Bone marrow examination is not mandated except if required as part of clinical trial, or in advanced disease where staging PET-CT has not been performed ADDIN EN.CITE El-Galaly20121340[1]1340134017El-Galaly, Tarec ChristofferdAmore, FrancescoMylam, Karen Juulde Nully Brown, PeterBgsted, MartinBukh, AnneSpecht, LenaLoft, AnnikaIyer, VictorHjorthaug, KarinNielsen, Anne LerbergChristiansen, IlseMadsen, CharlotteJohnsen, Hans-ErikHutchings, MartinRoutine Bone Marrow Biopsy Has Little or No Therapeutic Consequence for Positron Emission Tomography/Computed TomographyStaged Treatment-Naive Patients With Hodgkin LymphomaJournal of Clinical OncologyJournal of Clinical Oncology2012November 13, 2012http://jco.ascopubs.org/content/early/2012/11/13/JCO.2012.42.4036.abstract10.1200/jco.2012.42.4036[HYPERLINK \l "_ENREF_1" \o "El-Galaly, 2012 #1340"1].
Consider baseline lung function for patients receiving bleomycin. The risk of bleomycin toxicity is significantly increased in smokers and patients over the age of 60 years.
Consider baseline cardiac assessment (ECG, echo or MUGA) for all patients receiving anthracyclines and/or mediastinal radiotherapy, and this is mandated in patients with cardiac risk factors or over the age of 70 yrs.
The requirement for irradiated blood products should be registered with the Blood Transfusion Service.
Referral for discussion of fertility preservation options where relevant (see intranet for details including referral form and required pre-referral investigations)
Information Required at MDT
AWLP report (if final report not available at the time of commencing treatment the case should be re-listed when the final report is issued in order to complete registration and ensure no changes to treatment plan are required)
Ann Arbor staging information including PET-CT result
Risk grouping early (stage I-IIA, presence or absence of risk factors) or advanced (stage 2B+)
Performance status/relevant co-morbidities
Clinical trial eligibility
Fertility preservation options offered/completed
Referral to TYA MDT where appropriate
Treatment of Classical HL
Early stage stage I-IIA
The UK convention has been to designate all patients with stage I-IIA disease as early stage, where the German Hodgkin Study Group stratifies patients according to the presence or absence of the following risk factors:
Mediastinal bulk ( e" o n e t h i r d t r a n s v e r s e t h o r a c i c d i a m e t e r )
e"3 n o d a l a r e a s
E S R e"5 0 w i t h o u t B s y m p t o m s , o r E S R e"3 0 w i t h B s y m p t o m s
E x t r a - n o d a l s i t e o f d i s e a s e
C o m b i n e d m o d a l i t y t r e a t m e n t r e m a i n s t h e s t a n d a r d a p p r o a c h , w i t h p r o g r e s s i o n f r e e s u r v i v a l r a n g i n g f r o m 9 0 - 9 5 % .
E a rly stage I-IIA, no risk factors
2 cycles ABVD and 20 Gy IFRT ADDIN EN.CITE Engert2010675[2]67567517Engert, AndreasPltschow, AnnetteEich, Hans TheodorLohri, AndreasDrken, BerndBorchmann, PeterBerger, BernhardGreil, RichardWillborn, Kay C.Wilhelm, MartinDebus, JrgenEble, Michael J.Skler, MartinHo, AntonyRank, AndreasGanser, ArnoldTrmper, LorenzBokemeyer, CarstenKirchner, HartmutSchubert, JrgKrl, ZdenekFuchs, MichaelMller-Hermelink, Hans-KonradMller, Rolf-PeterDiehl, VolkerReduced Treatment Intensity in Patients with Early-Stage Hodgkin's LymphomaNew England Journal of MedicineNew England Journal of Medicine640-65236372010http://www.nejm.org/doi/full/10.1056/NEJMoa1000067doi:10.1056/NEJMoa1000067[HYPERLINK \l "_ENREF_2" \o "Engert, 2010 #675"2]
Early stage with risk factors
4 cycles ABVD and 30 Gy IFRT ADDIN EN.CITE von Tresckow20121065[3]1065106517von Tresckow, BastianPltschow, AnnetteFuchs, MichaelKlimm, BeateMarkova, JanaLohri, AndreasKral, ZdenekGreil, RichardTopp, Max S.Meissner, JuliaZijlstra, Jose M.Soekler, MartinStein, HaraldEich, Hans T.Mueller, Rolf P.Diehl, VolkerBorchmann, PeterEngert, AndreasDose-Intensification in Early Unfavorable Hodgkin's Lymphoma: Final Analysis of the German Hodgkin Study Group HD14 TrialJournal of Clinical OncologyJournal of Clinical Oncology2012January 23, 2012http://jco.ascopubs.org/content/early/2012/01/23/JCO.2011.38.5807.abstract10.1200/jco.2011.38.5807[HYPERLINK \l "_ENREF_3" \o "von Tresckow, 2012 #1065"3]
For these patients, once the treatment plan is decided, no interim assessment of response is required unless there is clinical concern. Discussion with and referral to a clinical oncologist is recommended prior to starting treatment.
A chemotherapy-only approach is an alternative strategy which may allow omission of RT following discussion of risk/benefit ADDIN EN.CITE Armitage20101849[4]1849184917Armitage, James O.Early-Stage Hodgkin's LymphomaNew England Journal of MedicineNew England Journal of Medicine653-6623637201020818856http://www.nejm.org/doi/full/10.1056/NEJMra1003733doi:10.1056/NEJMra1003733[HYPERLINK \l "_ENREF_4" \o "Armitage, 2010 #1849"4]. This may be because the risk of late effects from radiotherapy are considered to outweigh the increased risk of relapse, and should be decided upfront. Patients must be counselled with respect to the small increase in relapse risk. Interim PET request must state that this is for consideration of de-escalation for responders.
NCRI RAPID study for early stage HL I-IIA, non bulky, reported on results after 3 cycles of ABVD ADDIN EN.CITE Radford20121561[5]1561156117Radford, J AInvolved Field Radiotherapy Versus No Further Treatment in Patients with Clinical Stages IA and IIA Hodgkin Lymphoma and a Negative PET Scan After 3 Cycles ABVD. Results of the UK NCRI RAPID TrialASH Annual Meeting AbstractsASH Annual Meeting Abstracts2012[HYPERLINK \l "_ENREF_5" \o "Radford, 2012 #1561"5]
Interim PET is performed from day 9-13 after cycle 3B
If PET negative (Deauville score 1-2) after 3 cycles of ABVD, patients receiving no further treatment had a 3 yr progression free survival of 91% compared to 97% for pts receiving 30 Gy IFRT.
If PET positive (score 3 or more) for 1 further cycle of ABVD and 30 Gy IFRT. Expected early PFS for this group is 86.2%.
Patients with early relapse in the initially involved site have received successful salvage treatments which include involved field radiotherapy, BEACOPP-based regimes, with a small proportion having high dose chemotherapy.
Await publication and longer term follow up data.
Advanced stage
The standard treatment is considered 6-8 cycles of ABVD, with recent clinical trials using 6 cycles in the standard arm.
There is published evidence that a positive interim PET scan after 2 cycles of ABVD predicts a poor outcome with ABVD alone ADDIN EN.CITE Hutchings2006601[6]60160117Hutchings, MartinLoft, AnnikaHansen, MadsPedersen, Lars MllerBuhl, ThoraJurlander, JesperBuus, SimonKeiding, SusanneD'Amore, FrancescoBoesen, Anne-MarieBerthelsen, Anne KiilSpecht, LenaFDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphomaBloodBlood52-5910712006January 1, 2006http://bloodjournal.hematologylibrary.org/content/107/1/52.abstract10.1182/blood-2005-06-2252[HYPERLINK \l "_ENREF_6" \o "Hutchings, 2006 #601"6], though there is as yet no evidence that changing therapy on this basis is beneficial.
An inadequate response to 2 cycles ABVD may be considered a basis to escalate treatment in fit patients.
If a patient is fit for escalation, an interim PET scan may be requested after 2 cycles of ABVD, and the indication made clear on the request form.
If PET positive (Deauville score 4-5), particularly with an inadequate CT response, consider intensification to escalated BEACOPP. Imaging should be reviewed at the Lymphoma MDT, and management plan discussed.
If PET negative (Deauville score 3 or less), continue with a further 4 cycles of ABVD.
If there is clinical or radiological evidence of bleomycin toxicity, consider omission of bleomycin and continue with AVD, or change chemotherapy regime if necessary.
Interim PET scans in patients who did not have a staging PET scan should be interpreted with caution, and the default position would be to give 6 cycles ABVD (if responding) and reassess at the end of treatment.
Interim PET scans should not be undertaken in patients unsuitable for intensification.
For patients presenting with bulky mediastinal masses, consolidation RT (30 Gy) to the residual mass should be considered at the end of planned chemotherapy, prior to PET re-evaluation.
ABVD chemotherapy (cycle repeats every 28 days)
Doxorubicin 25 mg/m2 iv days 1, 15
Bleomycin 10,000 units/m2 iv days 1, 15
Vinblastine 6 mg/m2 iv days 1, 15
Dacarbazine 375 mg/m2 iv days 1, 15
This will be given at full dose and on schedule, regardless of blood count. Growth factors may be used at the discretion of clinicians but are not routinely advised ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_7" \o "Boleti, 2007 #1640"7, HYPERLINK \l "_ENREF_8" \o "Vakkalanka, 2011 #1250"8]
Escalated BEACOPP (Cycle repeats every 21 days)
Doxorubicin 35 mg/m2 iv day 1
Cyclophosphamide 1250 mg/m2 iv day 1
Etoposide 200 mg/m2 iv days 1-3
Procarbazine 100 mg/m2 po days 1-7
Prednisolone 40 mg/m2 po days 1-14
Bleomycin 10,000 units/m2 iv day 8
Vincristine 1.4 mg/m2 iv day 8, maximum 2 mg
G-CSF 263/300mcg s/c day 9 -13 or PEG-filgrastim 6 mg single dose .
Radiotherapy
Published guidelines now recommend the use of involved node radiotherapy (INRT) or involved site radiotherapy (ISRT) instead of involved field radiotherapy (IFRT) ADDIN EN.CITE Girinsky2006598[9]59859817Girinsky, Theodorevan der Maazen, RichardSpecht, LenaAleman, BerthePoortmans, PhilipLievens, YolandeMeijnders, PaulGhalibafian, MithraMeerwaldt, JacobusNoordijk, EvertInvolved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: Concepts and guidelinesRadiotherapy and OncologyRadiotherapy and Oncology270-277793Hodgkin lymphomaInvolved-node radiotherapyInvolved-field radiation treatmentCombined modality treatment20060167-8140http://www.sciencedirect.com/science/article/pii/S016781400600204010.1016/j.radonc.2006.05.015[HYPERLINK \l "_ENREF_9" \o "Girinsky, 2006 #598"9] ADDIN EN.CITE Specht20131665[10]1665166517Specht, L.Yahalom, J.Illidge, T.Berthelsen, A. K.Constine, L. S.Eich, H. T.Girinsky, T.Hoppe, R. T.Mauch, P.Mikhaeel, N. G.Ng, A.Department of Oncology and Hematology, Rigshospitalet, University of Copenhagen, Denmark. Electronic address: lena.specht@regionh.dk.Modern Radiation Therapy for Hodgkin Lymphoma: Field and Dose Guidelines From the International Lymphoma Radiation Oncology Group (ILROG)Int J Radiat Oncol Biol PhysInt J Radiat Oncol Biol Phys2013/06/252013Jun 181879-355X (Electronic)
0360-3016 (Linking)2379051210.1016/j.ijrobp.2013.05.005NLMEng[HYPERLINK \l "_ENREF_10" \o "Specht, 2013 #1665"10]. This allows for treatment of smaller volumes around originally involved lymph nodes and may reduce the risk of late effects. However, if pre-treatment imaging is not available or did not include a PET-CT scan, or there is uncertainty about the extent of involvement, then the default remains IFRT. Ideally patients should have diagnostic scans in the same position as the radiotherapy planning scan, and the latter should be performed with iv contrast.
Please refer to RT protocol for more details.
Older/comorbid patients
If not fit for ABVD, consider AVD, ChlVPP chemotherapy ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_11" \o "Selby, 1990 #1642"11, HYPERLINK \l "_ENREF_12" \o "Group, 1995 #1641"12] or VEPEMB ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_13" \o "Proctor, 2012 #1643"13].
Patients with stage IA non bulky disease may be treated with IFRT alone.
ChlVPP 28 day cycle
Chlorambucil 6 mg/m2 po od days 1-14
Vinblastine 6 mg/m2 capped at 10 mg iv days 1 and 8
Procarbazine 100 mg/m2 od capped at 200 mg po days 1-14
Prednisolone 40 mg/m2 po days 1-14
End of treatment assessment
For patients who have had a negative interim PET scan, this does not need to be repeated, but an end of treatment contrast-enhanced CT scan (4-6 weeks post chemotherapy) should be done as a baseline for follow-up, and to exclude progressive disease.
If a PET scan is required for response assessment on completion of all therapy, this should be done at 6-8 wks post chemotherapy, or 8-12 wks post radiotherapy ADDIN EN.CITE ADDIN EN.CITE.DATA [HYPERLINK \l "_ENREF_14" \o "Cheson, 2007 #1562"14, HYPERLINK \l "_ENREF_15" \o "Meignan, 2012 #1564"15].
Patients with refractory/progressive/relapsed disease ADDIN EN.CITE Collins20131854[16]1854185417Collins, Graham P.Parker, Anne N.Pocock, ChristopherKayani, IrfanSureda, AnnaIllidge, TimArdeshna, KiritLinch, David C.Peggs, Karl S.On behalf of the British Committee for Standards in, Haematologythe British Society of, BloodMarrow, TransplantationGuideline on the management of primary resistant and relapsed classical Hodgkin lymphomaBritish Journal of HaematologyBritish Journal of Haematologyn/a-n/aHodgkin lymphomarelapsechemotherapytransplantation20131365-2141http://dx.doi.org/10.1111/bjh.1258210.1111/bjh.12582[HYPERLINK \l "_ENREF_16" \o "Collins, 2013 #1854"16]
Strong consideration should be given for biopsy to confirm refractory/progressive/relapsed disease.
Prognostic factors
Does the patient have primary progressive/refractory disease, early relapse (within 12 months of complete remission) or late relapse (more than 12 months since complete remission)? Has the patient already had escalation of therapy as part of first line treatment?
Primary consideration:
Is patient fit for high dose chemotherapy and autograft?
Discuss at MDT meeting with transplant team.
The aim of salvage chemotherapy is to debulk and confirm chemo-sensitive disease suitable for high dose therapy.
Baseline and response assessment PET scans are required.
Metabolic remission on PET prior to autograft is associated with an improved outcome and should be the aim of salvage treatment ADDIN EN.CITE Moskowitz20121088[17]1088108817Moskowitz, Craig H.Matasar, Matt J.Zelenetz, Andrew D.Nimer, Stephen D.Gerecitano, JohnHamlin, PaulHorwitz, StevenMoskowitz, Alison J.Noy, ArielaPalomba, LiaPerales, Miguel-AngelPortlock, CarolStraus, DavidMaragulia, Jocelyn C.Schoder, HeikoYahalom, JoachimNormalization of pre-ASCT, FDG-PET imaging with second-line, noncross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphomaBloodBlood1665-167011972012February 16, 2012http://bloodjournal.hematologylibrary.org/content/119/7/1665.abstract10.1182/blood-2011-10-388058[HYPERLINK \l "_ENREF_17" \o "Moskowitz, 2012 #1088"17].
Arrangements should be made for stem cell collection.
Salvage therapy
The choice of salvage therapy including a clinical trial option may depend on any existing comorbidities eg renal impairment.
Recommended regimes include:
IGEV
ESHAP
ICE
miniBEAM
GemP
Suggested treatment protocol:
Cycle 1
Cycle 2
Stem cell collection
CT evaluation if good PR:
Cycle 3
PET-CT if metabolic CR, then transplant work up and admission for HDC/ASCT
Avoid doing PET at time of G-CSF use for stem cell mobilisation, or make sure that this information is detailed on request form.
Poor responders:
If PET positive depending on degree of response (PR, SD or PD) and fitness of patient:
discuss with transplant team
consider potential for allograft (sibling/MUD).
Patients who have previously received intensification as part of first line therapy may be considered to have failed 2 lines of treatment by this stage, and brentuximab should be considered.
Brentuximab
1.8 mg/kg, capped at a weight of 100 kg, iv day 1 on a 21 day cycle
2nd line salvage
As listed above
For progressive disease following 2nd line salvage, consider best supportive care, palliative radiotherapy or chemotherapy or brentuximab to achieve stable disease if allograft is still a potential option.
Consideration of allograft over autograft if:
Chemo-refractory HL and stable or slowly progressive disease after at least 1 line of salvage therapy
Adequate performance status/no significant co-morbidities
Suitable donor options
Relapse post-autograft
Prognostic factors include duration of remission, age and extent of relapse.
Consider allograft if donor options available,.
Treatment options include brentuximab as a bridge to transplant.
Relapse post-allograft
PET-directed DLI +/- brentuximab may be considered.
Palliative treatment
For patients not suitable for curative options due to progressive disease or poor performance status.
Best supportive care (BSC) with early involvement of community cancer teams and palliative care services is recommended.
Patients may have active surveillance and BSC, and treatment offered at time of symptomatic progression.
Treatment options:
ChlVPP
CCEP
Bendamustine 120 mg/m2 days1,2 on a 28 day cycle ADDIN EN.CITE Moskowitz20131531[18]1531153117Moskowitz, Alison J.Hamlin, Paul A.Perales, Miguel-AngelGerecitano, JohnHorwitz, Steven M.Matasar, Matthew J.Noy, ArielaPalomba, Maria LiaPortlock, Carol S.Straus, David J.Graustein, TriciaZelenetz, Andrew D.Moskowitz, Craig H.Phase II Study of Bendamustine in Relapsed and Refractory Hodgkin LymphomaJournal of Clinical OncologyJournal of Clinical Oncology456-4603142013February 1, 2013http://jco.ascopubs.org/content/31/4/456.abstract10.1200/jco.2012.45.3308[HYPERLINK \l "_ENREF_18" \o "Moskowitz, 2013 #1531"18]
Radiotherapy
Clinical trial
Response assessment should be performed according to published criteria:
International Working Group response criteria - Cheson ADDIN EN.CITE Cheson20071562[14]1562156217Cheson, Bruce D.Pfistner, BeateJuweid, Malik E.Gascoyne, Randy D.Specht, LenaHorning, Sandra J.Coiffier, BertrandFisher, Richard I.Hagenbeek, AntonZucca, EmanueleRosen, Steven T.Stroobants, SigridLister, T. AndrewHoppe, Richard T.Dreyling, MartinTobinai, KenseiVose, Julie M.Connors, Joseph M.Federico, MassimoDiehl, VolkerRevised Response Criteria for Malignant LymphomaJournal of Clinical OncologyJournal of Clinical Oncology579-5862552007February 10, 2007http://jco.ascopubs.org/content/25/5/579.abstract10.1200/jco.2006.09.2403[HYPERLINK \l "_ENREF_14" \o "Cheson, 2007 #1562"14]
Deauville scoring for PET reporting ADDIN EN.CITE Meignan20121564[15]1564156417Meignan, MichelGallamini, AndreaItti, EmmanuelBarrington, SallyHaioun, CorinnePolliack, AaronReport on the Third International Workshop on Interim Positron Emission Tomography in Lymphoma held in Menton, France, 2627 September 2011 and Menton 2011 consensusLeukemia & LymphomaLeukemia & Lymphoma1876-18815310201222432519http://informahealthcare.com/doi/abs/10.3109/10428194.2012.677535doi:10.3109/10428194.2012.677535[HYPERLINK \l "_ENREF_15" \o "Meignan, 2012 #1564"15]
Radiotherapy to the mediastinum
In 2003, the Department of Health launched a notification and management programme for women treated for HL with supradiaphragmatic radiotherapy under the age of 36 years ADDIN EN.CITE DOH20031563[19]1563156317DOHIncreased Risk of Breast Cancer after Radiotherapy for Hodgkins Disease: Patient Notification Exercise & Updated Toolkit2003[HYPERLINK \l "_ENREF_19" \o "DOH, 2003 #1563"19]. Women were informed that if treated in childhood or young adulthood, they had a 1 in 3 to 1 in 7 risk of developing breast cancer by age 40-50, against a general population risk of 1 in 50 by age 50.
Annual breast screening is offered 8 years post-radiotherapy, or starting at age 25; by MRI if aged under 30 years and by mammography if aged 30-50. Standard 3-yearly mammography is performed after age 50.
All patients eligible for screening should be referred to the lead clinical oncologist in the Network for registration on the Breast Test Wales database. Patients treated for NHL with curative intent who are also considered at risk will be included.
At the time of initiation of screening, patients are offered a consultation and will be required to sign a consent form.
South East Eve Gallop-Evans
South West Roger Taylor
North Wales Angel Garcia
Radiotherapy to superior mediastinum/neck
This confers a late risk of hypothyroidism, and lifelong annual monitoring of TFTs is recommended.
Follow up on completion of treatment
Early stage
1st year 3 monthly
2nd year 6 monthly
3rd year annually until 5 yrs then discharge
Advanced stage
1st year 3 monthly
2nd year 4 monthly
3rd year 6 monthly
4th year annually for 5 yrs then discharge
There is no evidence for routine surveillance imaging during clinical remission. ADDIN EN.CITE Radford1997331[20]33133117Radford, J AEardley, AWoodman, CCrowther, DFollow up policy after treatment for Hodgkin's disease: too many clinic visits and routine tests? A review of hospital recordsBMJBMJ34331470771997February 1, 1997http://www.bmj.com/content/314/7077/343.2.abstract[HYPERLINK \l "_ENREF_20" \o "Radford, 1997 #331"20]
Nodular lymphocyte predominant Hodgkin lymphoma
NLPHL may present as slowly progressive lymphadenopathy at a peripheral site such as the neck, axilla or groin, and rarely involves mediastinal nodes. It is more common in men in the 3rd or 4th decade. Expert haematopathology review is essential, as it can transform to T-cell rich B cell lymphoma. A retrospective analysis of 131 patients with early stage low-risk disease treated within clinical studies of the GHSG showed no difference in outcome between extended- or involved-field RT, or combined-modality treatment (Nogov et al., 2005). Local RT gives durable control, and given the predominantly peripheral sites involved, late effects are rare ADDIN EN.CITE Chen2010243[21]24324317Chen, Ronald C.Chin, Michael S.Ng, Andrea K.Feng, YangNeuberg, DonnaSilver, BarbaraPinkus, Geraldine S.Stevenson, Mary AnnMauch, Peter M.Early-Stage, Lymphocyte-Predominant Hodgkin's Lymphoma: Patient Outcomes From a Large, Single-Institution Series With Long Follow-UpJournal of Clinical OncologyJournal of Clinical Oncology136-1412812010January 1, 2010http://jco.ascopubs.org/content/28/1/136.abstract10.1200/jco.2009.24.0945[HYPERLINK \l "_ENREF_21" \o "Chen, 2010 #243"21]. Although the clinical behavior of NLPHL resembles that of a low grade B cell lymphoma, higher stages have traditionally been treated as for classical HL. The role of rituximab remains unclear but an alternative approach would be R-ABVD.
Paediatric treatment guidelines recommend a watch-and-wait strategy in patients who are PET-negative after surgical excision, and the current EuroNet-L1 study is also testing the use of a non-anthracycline based chemotherapy regime for early stage patients below the age of 18 years.
Recommendation
Stage IA on PET-CT, non-bulky If no residual disease, observation alone may be considered; otherwise IFRT/ISRT 30 Gy in 15 fractions.
Stage IIA non-bulky 2 cycles ABVD and 20 Gy IFRT/ISRT
Stage I-IIA bulky 4 cycles ABVD and 30 Gy IFRT/ISRT
Stage III-IV 6 cycles ABVD with/without rituximab
References
Published standards:
National standards for teenagers and young adults with cancer aged 16-24 years.
BCSH Guidelines
ADDIN EN.REFLIST 1. El-Galaly, T.C., et al., Routine Bone Marrow Biopsy Has Little or No Therapeutic Consequence for Positron Emission Tomography/Computed TomographyStaged Treatment-Naive Patients With Hodgkin Lymphoma. Journal of Clinical Oncology, 2012.
2. Engert, A., et al., Reduced Treatment Intensity in Patients with Early-Stage Hodgkin's Lymphoma. New England Journal of Medicine, 2010. 363(7): p. 640-652.
3. von Tresckow, B., et al., Dose-Intensification in Early Unfavorable Hodgkin's Lymphoma: Final Analysis of the German Hodgkin Study Group HD14 Trial. Journal of Clinical Oncology, 2012.
4. Armitage, J.O., Early-Stage Hodgkin's Lymphoma. New England Journal of Medicine, 2010. 363(7): p. 653-662.
5. Radford, J.A., Involved Field Radiotherapy Versus No Further Treatment in Patients with Clinical Stages IA and IIA Hodgkin Lymphoma and a Negative PET Scan After 3 Cycles ABVD. Results of the UK NCRI RAPID Trial. ASH Annual Meeting Abstracts, 2012.
6. Hutchings, M., et al., FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood, 2006. 107(1): p. 52-59.
7. Boleti, E. and G.M. Mead, ABVD for Hodgkin's lymphoma: full-dose chemotherapy without dose reductions or growth factors. ANN ONCOL, 2007. 18(2): p. 376-80.
8. Vakkalanka, B. and B.K. Link, Neutropenia and Neutropenic Complications in ABVD Chemotherapy for Hodgkin Lymphoma. Adv Hematol, 2011. 2011.
9. Girinsky, T., et al., Involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: Concepts and guidelines. Radiotherapy and Oncology, 2006. 79(3): p. 270-277.
10. Specht, L., et al., Modern Radiation Therapy for Hodgkin Lymphoma: Field and Dose Guidelines From the International Lymphoma Radiation Oncology Group (ILROG). Int J Radiat Oncol Biol Phys, 2013.
11. Selby, P., et al., ChlVPP combination chemotherapy for Hodgkin's disease: long-term results. Br J Cancer, 1990. 62(2): p. 279-85.
12. Group, T.I.C.T., ChlVPP therapy for Hodgkin's disease: Experience of 960 patients. Annals of Oncology, 1995. 6(2): p. 167-172.
13. Proctor, S.J., et al., Evaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD study. Blood, 2012. 119(25): p. 6005-15.
14. Cheson, B.D., et al., Revised Response Criteria for Malignant Lymphoma. Journal of Clinical Oncology, 2007. 25(5): p. 579-586.
15. Meignan, M., et al., Report on the Third International Workshop on Interim Positron Emission Tomography in Lymphoma held in Menton, France, 2627 September 2011 and Menton 2011 consensus. Leukemia & Lymphoma, 2012. 53(10): p. 1876-1881.
16. Collins, G.P., et al., Guideline on the management of primary resistant and relapsed classical Hodgkin lymphoma. British Journal of Haematology, 2013: p. n/a-n/a.
17. Moskowitz, C.H., et al., Normalization of pre-ASCT, FDG-PET imaging with second-line, noncross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma. Blood, 2012. 119(7): p. 1665-1670.
18. Moskowitz, A.J., et al., Phase II Study of Bendamustine in Relapsed and Refractory Hodgkin Lymphoma. Journal of Clinical Oncology, 2013. 31(4): p. 456-460.
19. DOH, Increased Risk of Breast Cancer after Radiotherapy for Hodgkins Disease: Patient Notification Exercise & Updated Toolkit. 2003.
20. Radford, J.A., et al., Follow up policy after treatment for Hodgkin's disease: too many clinic visits and routine tests? A review of hospital records. BMJ, 1997. 314(7077): p. 343.
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5 5 / ytr&# T D Boleti20071640[7, 8]1640164017Boleti, E.Mead, G. M.Department of Medical Oncology, Southampton General Hospital, CRUK Clinical Centre, Southampton, Hampshire, UK. ekaterini.boleti@suht.swest.nhs.ukABVD for Hodgkin's lymphoma: full-dose chemotherapy without dose reductions or growth factorsANN ONCOLANN ONCOL376-801822006/10/31AdolescentAdultAgedAntineoplastic Combined Chemotherapy Protocols/ administration & dosageBleomycin/administration & dosageDacarbazine/administration & dosageDisease-Free SurvivalDose-Response Relationship, DrugDoxorubicin/administration & dosageFemaleGranulocytesHodgkin Disease/ drug therapy/metabolism/pathologyHumansIntercellular Signaling Peptides and Proteins/ metabolismMaleMiddle AgedRetrospective StudiesTreatment OutcomeVinblastine/administration & dosage2007Feb0923-7534 (Print)
0923-7534 (Linking)1707193810.1093/annonc/mdl397NLMengVakkalanka201112501250125017Vakkalanka, B.Link, B. K.Department of Internal Medicine, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USANeutropenia and Neutropenic Complications in ABVD Chemotherapy for Hodgkin LymphomaAdv HematolAdv Hematol201120111687-9104 (Print)
1687-9112 (Electronic)21687649288863310.1155/2011/656013NLMeng D Boleti20071640[7, 8]1640164017Boleti, E.Mead, G. M.Department of Medical Oncology, Southampton General Hospital, CRUK Clinical Centre, Southampton, Hampshire, UK. ekaterini.boleti@suht.swest.nhs.ukABVD for Hodgkin's lymphoma: full-dose chemotherapy without dose reductions or growth factorsANN ONCOLANN ONCOL376-801822006/10/31AdolescentAdultAgedAntineoplastic Combined Chemotherapy Protocols/ administration & dosageBleomycin/administration & dosageDacarbazine/administration & dosageDisease-Free SurvivalDose-Response Relationship, DrugDoxorubicin/administration & dosageFemaleGranulocytesHodgkin Disease/ drug therapy/metabolism/pathologyHumansIntercellular Signaling Peptides and Proteins/ metabolismMaleMiddle AgedRetrospective StudiesTreatment OutcomeVinblastine/administration & dosage2007Feb0923-7534 (Print)
0923-7534 (Linking)1707193810.1093/annonc/mdl397NLMengVakkalanka201112501250125017Vakkalanka, B.Link, B. K.Department of Internal Medicine, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USANeutropenia and Neutropenic Complications in ABVD Chemotherapy for Hodgkin LymphomaAdv HematolAdv Hematol201120111687-9104 (Print)
1687-9112 (Electronic)21687649288863310.1155/2011/656013NLMeng D Selby19901642[11, 12]1642164217Selby, P.Patel, P.Milan, S.Meldrum, M.Mansi, J.Mbidde, E.Brada, M.Perren, T.Forgeson, G.Gore, M.et al.,Section of Medicine, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, UK.ChlVPP combination chemotherapy for Hodgkin's disease: long-term resultsBr J CancerBr J Cancer279-856221990/08/01AdolescentAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy Protocols/ therapeutic use/toxicityBone Marrow Diseases/ drug therapy/pathologyChlorambucil/administration & dosage/toxicityDeathFemaleHodgkin Disease/ drug therapy/pathologyHumansLeukemia, Myeloid/chemically inducedLiver Neoplasms/ drug therapy/pathologyLung Neoplasms/ drug therapy/pathologyMaleMiddle AgedMultivariate AnalysisNeoplasm StagingPrednisolone/administration & dosage/toxicityProcarbazine/administration & dosage/toxicityVinblastine/administration & dosage/toxicity1990Aug0007-0920 (Print)
0007-0920 (Linking)23867441971832NLMengGroup199516411641164117The International ChlVPP Treatment GroupChlVPP therapy for Hodgkin's disease: Experience of 960 patientsAnnals of OncologyAnnals of Oncology167-172621995February 1, 1995http://annonc.oxfordjournals.org/content/6/2/167.abstract D Selby19901642[11, 12]1642164217Selby, P.Patel, P.Milan, S.Meldrum, M.Mansi, J.Mbidde, E.Brada, M.Perren, T.Forgeson, G.Gore, M.et al.,Section of Medicine, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, UK.ChlVPP combination chemotherapy for Hodgkin's disease: long-term resultsBr J CancerBr J Cancer279-856221990/08/01AdolescentAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy Protocols/ therapeutic use/toxicityBone Marrow Diseases/ drug therapy/pathologyChlorambucil/administration & dosage/toxicityDeathFemaleHodgkin Disease/ drug therapy/pathologyHumansLeukemia, Myeloid/chemically inducedLiver Neoplasms/ drug therapy/pathologyLung Neoplasms/ drug therapy/pathologyMaleMiddle AgedMultivariate AnalysisNeoplasm StagingPrednisolone/administration & dosage/toxicityProcarbazine/administration & dosage/toxicityVinblastine/administration & dosage/toxicity1990Aug0007-0920 (Print)
0007-0920 (Linking)23867441971832NLMengGroup199516411641164117The International ChlVPP Treatment GroupChlVPP therapy for Hodgkin's disease: Experience of 960 patientsAnnals of OncologyAnnals of Oncology167-172621995February 1, 1995http://annonc.oxfordjournals.org/content/6/2/167.abstract D Proctor20121643[13]1643164317Proctor, S. J.Wilkinson, J.Jones, G.Watson, G. C.Lucraft, H. H.Mainou-Fowler, T.Culligan, D.Galloway, M. J.Wood, K. M.McNally, R. J.James, P. W.Goodlad, J. R.Academic Haematology, Northern Institute of Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom. s.j.proctor@newcastle.ac.ukEvaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD studyBloodBlood6005-15119252012/05/12Age FactorsAgedAged, 80 and overClinical Trials, Phase II as Topic/statistics & numerical dataCohort StudiesComorbidityFemaleHodgkin Disease/ diagnosis/epidemiology/mortality/ therapyHumansMaleMiddle AgedPrognosisRandomized Controlled Trials as Topic/statistics & numerical dataSurvival AnalysisTreatment Outcome2012Jun 211528-0020 (Electronic)
0006-4971 (Linking)2257717710.1182/blood-2011-12-396556NLMeng D Proctor20121643[13]1643164317Proctor, S. J.Wilkinson, J.Jones, G.Watson, G. C.Lucraft, H. H.Mainou-Fowler, T.Culligan, D.Galloway, M. J.Wood, K. M.McNally, R. J.James, P. W.Goodlad, J. R.Academic Haematology, Northern Institute of Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom. s.j.proctor@newcastle.ac.ukEvaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD studyBloodBlood6005-15119252012/05/12Age FactorsAgedAged, 80 and overClinical Trials, Phase II as Topic/statistics & numerical dataCohort StudiesComorbidityFemaleHodgkin Disease/ diagnosis/epidemiology/mortality/ therapyHumansMaleMiddle AgedPrognosisRandomized Controlled Trials as Topic/statistics & numerical dataSurvival AnalysisTreatment Outcome2012Jun 211528-0020 (Electronic)
0006-4971 (Linking)2257717710.1182/blood-2011-12-396556NLMeng D Cheson20071562[14, 15]1562156217Cheson, Bruce D.Pfistner, BeateJuweid, Malik E.Gascoyne, Randy D.Specht, LenaHorning, Sandra J.Coiffier, BertrandFisher, Richard I.Hagenbeek, AntonZucca, EmanueleRosen, Steven T.Stroobants, SigridLister, T. AndrewHoppe, Richard T.Dreyling, MartinTobinai, KenseiVose, Julie M.Connors, Joseph M.Federico, MassimoDiehl, VolkerRevised Response Criteria for Malignant LymphomaJournal of Clinical OncologyJournal of Clinical Oncology579-5862552007February 10, 2007http://jco.ascopubs.org/content/25/5/579.abstract10.1200/jco.2006.09.2403Meignan201215641564156417Meignan, MichelGallamini, AndreaItti, EmmanuelBarrington, SallyHaioun, CorinnePolliack, AaronReport on the Third International Workshop on Interim Positron Emission Tomography in Lymphoma held in Menton, France, 26–27 September 2011 and Menton 2011 consensusLeukemia & LymphomaLeukemia & Lymphoma1876-18815310201222432519http://informahealthcare.com/doi/abs/10.3109/10428194.2012.677535doi:10.3109/10428194.2012.677535 D Cheson20071562[14, 15]1562156217Cheson, Bruce D.Pfistner, BeateJuweid, Malik E.Gascoyne, Randy D.Specht, LenaHorning, Sandra J.Coiffier, BertrandFisher, Richard I.Hagenbeek, AntonZucca, EmanueleRosen, Steven T.Stroobants, SigridLister, T. AndrewHoppe, Richard T.Dreyling, MartinTobinai, KenseiVose, Julie M.Connors, Joseph M.Federico, MassimoDiehl, VolkerRevised Response Criteria for Malignant LymphomaJournal of Clinical OncologyJournal of Clinical Oncology579-5862552007February 10, 2007http://jco.ascopubs.org/content/25/5/579.abstract10.1200/jco.2006.09.2403Meignan201215641564156417Meignan, MichelGallamini, AndreaItti, EmmanuelBarrington, SallyHaioun, CorinnePolliack, AaronReport on the Third International Workshop on Interim Positron Emission Tomography in Lymphoma held in Menton, France, 26–27 September 2011 and Menton 2011 consensusLeukemia & LymphomaLeukemia & Lymphoma1876-18815310201222432519http://informahealthcare.com/doi/abs/10.3109/10428194.2012.677535doi:10.3109/10428194.2012.677535 ^$ 6 6 6 6 6 6 6 6 6 v v v v v v v v v 6 6 6 6 6 6 > 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 h H 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 2 0 @ P ` p 2 ( 0 @ P ` p 0 @ P ` p 0 @ P ` p 0 @ P ` p 0 @ P ` p 0 @ P ` p 8 X V ~ _HmH nH sH tH @ ` @ vc" N o r m a l CJ _HaJ mH sH tH B 2 B y9 0 H e a d i n g 3 $@& 5CJ" \aJ" D A` D
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