Protocol. Hematopoietic Stem-Cell Transplantation for Hodgkin Lymphoma

Transcription

1 Prtcl Hematpietic Stem-Cell Transplantatin fr Hdgkin Lymphma (80129) Medical Benefit Effective Date: 04/01/13 Next Review Date: 01/15 Preauthrizatin Yes Review Dates: 04/07, 05/08, 01/10, 01/11, 01/12, 01/13, 01/14 The fllwing Prtcl cntains medical necessity criteria that apply fr this service. It is applicable t Medicare Advantage prducts unless separate Medicare Advantage criteria are indicated. If the criteria are nt met, reimbursement will be denied and the patient cannt be billed. Preauthrizatin is required and must be btained thrugh Case Management. Please nte that payment fr cvered services is subject t eligibility and the limitatins nted in the patient s cntract at the time the services are rendered. Descriptin Hematpietic Stem-Cell Transplantatin Hematpietic stem-cell transplantatin (HSCT) refers t a prcedure in which hematpietic stem cells are infused t restre bne marrw functin in cancer patients wh receive bne-marrw-txic dses f cyttxic drugs with r withut whle-bdy radiatin therapy. Hematpietic stem cells may be btained frm the transplant recipient (autlgus HSCT) r frm a dnr (allgeneic HSCT). They can be harvested frm bne marrw, peripheral bld, r umbilical crd bld shrtly after delivery f nenates. Althugh crd bld is an allgeneic surce, the stem cells in it are antigenically naïve and thus are assciated with a lwer incidence f rejectin r graft-versus-hst disease (GVHD). Immunlgic cmpatibility between infused hematpietic stem cells and the recipient is nt an issue in autlgus HSCT. Hwever, immunlgic cmpatibility between dnr and patient is a critical factr fr achieving a gd utcme f allgeneic HSCT. Cmpatibility is established by typing f human leukcyte antigens (HLA) using cellular, serlgic, r mlecular techniques. HLA refers t the tissue type expressed at the Class I and Class II lci n chrmsme 6. Depending n the disease being treated, an acceptable dnr will match the patient at all r mst f the HLA lci (with the exceptin f umbilical crd bld). Cnventinal Preparative Cnditining fr HSCT The success f autlgus HSCT is predicated n the ability f cyttxic chemtherapy with r withut radiatin t eradicate cancerus cells frm the bld and bne marrw. This permits subsequent engraftment and reppulatin f bne marrw space with presumably nrmal hematpietic stem cells btained frm the patient prir t underging bne marrw ablatin. As a cnsequence, autlgus HSCT is typically perfrmed as cnslidatin therapy when the patient s disease is in cmplete remissin (CR). Patients wh underg autlgus HSCT are susceptible t chemtherapy-related txicities and pprtunistic infectins prir t engraftment, but nt GVHD. The cnventinal ( classical ) practice f allgeneic HSCT invlves administratin f cyttxic agents (e.g., cyclphsphamide, busulfan) with r withut ttal-bdy irradiatin at dses sufficient t destry endgenus hematpietic capability in the recipient. The beneficial treatment effect in this prcedure is due t a cmbinatin f initial eradicatin f malignant cells and subsequent graft-versus-malignancy (GVM) effect mediated by nn-self immunlgic effectr cells that develp after engraftment f allgeneic stem cells within the patient s bne marrw space. While the slwer GVM effect is cnsidered t be the ptentially curative cmpnent, it may be verwhelmed by extant disease withut the use f pretransplant cnditining. Hwever, intense cnditining regimens are limited t patients wh are sufficiently fit medically t tlerate substantial Page 1 f 6

2 adverse effects that include pre-engraftment pprtunistic infectins secndary t lss f endgenus bne marrw functin and rgan damage and failure caused by the cyttxic drugs. Furthermre, in any allgeneic HSCT, immunsuppressant drugs are required t minimize graft rejectin and GVHD, which als increases susceptibility f the patient t pprtunistic infectins. Reduced-Intensity Cnditining fr Allgeneic HSCT Reduced-intensity cnditining (RIC) refers t the pretransplant use f lwer dses r less intense regimens f cyttxic drugs r radiatin than are used in traditinal full-dse myelablative cnditining treatments. The gal f RIC is t reduce disease burden but als t minimize as much as pssible assciated treatment-related mrbidity and nn-relapse mrtality (NRM) in the perid during which the beneficial GVM effect f allgeneic transplantatin develps. Althugh the definitin f RIC remains arbitrary, with numerus versins emplyed, all seek t balance the cmpeting effects f NRM and relapse due t residual disease. RIC regimens can be viewed as a cntinuum in effects, frm nearly ttally myelablative t minimally myelablative with lymphablatin, with intensity tailred t specific diseases and patient cnditin. Patients wh underg RIC with allgeneic HSCT initially demnstrate dnr-cell engraftment and bne-marrw mixed chimerism. Mst will subsequently cnvert t full-dnr chimerism, which may be supplemented with dnr lymphcyte infusins t eradicate residual malignant cells. Fr the purpses f this Prtcl, the term reduced-intensity cnditining (RIC) will refer t all cnditining regimens intended t be nn-myelablative, as ppsed t fully myelablative (traditinal) regimens. Hdgkin Lymphma Hdgkin Lymphma (HL) is a relatively uncmmn B cell lymphma. In 2011, the estimated number f cases in the U.S. was apprximately 8,830 new diagnses and 1,300 deaths. (1) The disease has a bimdal distributin, with mst patients diagnsed between the ages f 15 and 30 years, with a secnd peak in adults aged 55 years and lder. The 2008 Wrld Health Organizatin (WHO) classificatin divides HL int tw main types (2): 1. Classical HL (CHL) Ndular sclersis Mixed cellularity Lymphcyte depleted Lymphcyte rich 2. Ndular Lymphcyte-Predminant HL (NLPHL) In Western cuntries, CHL accunts fr 95% f cases f HL and NLPHL nly 5%. (3) Classic HL is characterized by the presence f neplastic Reed-Sternberg cells in a backgrund f numerus nn-neplastic inflammatry cells. NLPHL lacks Reed-Sternberg cells but is characterized by the presence f lymphcytic and histicytic cells termed ppcrn cells. (3) The fllwing staging system fr HL recgnizes that the disease is thught t typically arise in a single lymph nde and spread t cntiguus lymph ndes with eventual invlvement f extrandal sites. The staging system attempts t distinguish patients with lcalized HL wh can be treated with extended field radiatin frm thse wh require systemic chemtherapy. Staging fr Hdgkin Lymphma Staging fr HL is based n the Ann Arbr staging system. Each stage is subdivided int A and B categries. A indicates n systemic symptms are present, and B indicates the presence f systemic symptms, including unexplained weight lss f mre than 10% f bdy weight, unexplained fevers, r drenching night sweats. (3) Page 2 f 6

3 Stage I Invlvement f a single lymph nde regin (I) r lcalized invlvement f a single extralymphatic rgan r site (IE) Stage II Invlvement f tw r mre lymph nde regins n the same side f the diaphragm (II) r lcalized invlvement f a single assciated extralymphatic rgan r site and its reginal lymph nde(s) with r withut invlvement f ther lymph nde regins n the same side f the diaphragm (IIE). The number f lymph nde regins invlved shuld be indicated by a subscript (e.g., II 2 ). Stage III Invlvement f lymph nde regins r structures n bth sides f the diaphragm. These patients are further subdivided as fllws: III-1: disease limited t spleen r upper abdmen III-2: periartic r pelvic nde invlvement Stage IV Disseminated (multifcal) invlvement f ne r mre extralymphatic rgans, with r withut assciated lymph nde invlvement, r islated extralymphatic rgan invlvement with distant (nnreginal) ndal invlvement. Patients with HL are generally classified int three grups: early-stage favrable (stage I II with n B symptms r large mediastinal lymphadenpathy), early-stage unfavrable (stage I II with large mediastinal mass, with r withut B symptms; stage IB IIB with bulky disease), and advanced-stage disease (stage III IV). (3) Patients with nnbulky stage IA r IIA disease are cnsidered t have clinical early-stage disease. These patients are candidates fr chemtherapy, cmbined mdality therapy, r radiatin therapy alne. (1) Patients with bvius stage III r IV disease, bulky disease (defined as a 10-cm mass r mediastinal disease with a transverse diameter exceeding 33% f the transthracic diameter), r the presence f B symptms will require cmbinatin chemtherapy with r withut additinal radiatin therapy. (1) HL is highly respnsive t cnventinal chemtherapy, and up t 80% f newly diagnsed patients can be cured with cmbinatin chemtherapy and/r radiatin therapy. Patients wh prve refractry r wh relapse after first-line therapy have a significantly wrse prgnsis. Primary refractry HL is defined as disease regressin f less than 50% after fur t six cycles f anthracycline-cntaining chemtherapy, disease prgressin during inductin therapy, r prgressin within 90 days after the cmpletin f first-line treatment. (4) In patients with relapse, the results f salvage therapy vary depending upn a number f prgnstic factrs, as fllws: the length f the initial remissin, stage at recurrence, and the severity f anemia at the time f relapse. (5) Early and late relapse are defined as less r mre than 12 mnths frm the time f remissin, respectively. Apprximately 70% f patients with late first relapse can be salvaged by autlgus HSCT but nt mre than 40% with early first relapse. (6) Only apprximately 25-35% f patients with primary prgressive r pr-risk recurrent HL achieve durable remissin after autlgus HSCT, with mst failures being due t disease prgressin after transplant. Mst relapses after transplant ccur within ne t tw years, and nce relapse ccurs pst-transplant, median survival is less than 12 mnths. Plicy (Frmerly Crprate Medical Guideline) Autlgus r myelablative allgeneic hematpietic stem-cell transplantatin (HSCT) may be cnsidered Page 3 f 6

4 medically necessary in patients with primary refractry r relapsed Hdgkin lymphma (HL). Tandem autlgus HSCT may be cnsidered medically necessary: in patients with primary refractry HL r in patients with relapsed disease with pr risk features wh d nt attain a cmplete remissin t cytreductive chemtherapy prir t transplantatin (see Plicy Guidelines). Reduced-intensity allgeneic HSCT may be cnsidered medically necessary t treat HL in patients: wh have failed a prir autlgus HSCT used t treat primary refractry r relapsed disease r in patients wh wuld therwise qualify fr a myelablative allgeneic transplant, but wuld be unable t tlerate a standard myelablative cnditining regimen (see Plicy Guidelines) r when insufficient stem cells are cllected fr an autlgus HSCT. Secnd autlgus stem-cell transplantatin fr relapsed lymphma after a prir autlgus HSCT is cnsidered investigatinal. Other uses f HSCT in patients with HL are cnsidered investigatinal, including, but nt limited t, initial therapy fr newly diagnsed disease t cnslidate a first cmplete remissin. Plicy Guideline In the Mrschhauser et al study f risk-adapted salvage treatment with single r tandem autlgus hematpietic stem-cell transplantatin (HSCT) fr first relapse r refractry Hdgkin lymphma (HL), (7) prrisk relapsed HL was defined as tw r mre f the fllwing risk factrs at first relapse: time t relapse less than 12 mnths, stage III r IV at relapse, and relapse within previusly irradiated sites. Primary refractry disease was defined as disease regressin less than 50% after fur t six cycles f dxrubicin-cntaining chemtherapy r disease prgressin during inductin r within 90 days after the end f first-line treatment. Sme patients fr whm a cnventinal myelablative alltransplant culd be curative may be cnsidered candidates fr reduced-intensity cnditining (RIC) allgeneic HSCT. These include thse with malignancies that are effectively treated with myelablative allgeneic transplantatin, but whse age (typically lder than 55 years) r cmrbidities (e.g., liver r kidney dysfunctin, generalized debilitatin, prir intensive chemtherapy, lw Karnfsky Perfrmance Status) preclude use f a standard myelablative cnditining regimen. The ideal allgeneic dnrs are human leukcyte antigen (HLA)-identical matched siblings. Related dnrs mismatched at ne lcus are als cnsidered suitable dnrs. A matched, unrelated dnr identified thrugh the Natinal Marrw Dnr Registry is typically the next ptin cnsidered. Recently, there has been interest in haplidentical dnrs, typically a parent r a child f the patient, with whm usually there is sharing f nly three f the six majr histcmpatibility antigens. The majrity f patients will have such a dnr; hwever, the risk f GVHD and verall mrbidity f the prcedure may be severe, and experience with these dnrs is nt as extensive as that with matched dnrs. Benefit Applicatin Individual transplant facilities may have their wn additinal requirements r prtcls that must be met in rder fr the patient t be eligible fr a transplant at their facility. Page 4 f 6

5 Medicare Advantage If a transplant is needed, we arrange t have the transplant center review and decide whether the patient is an apprpriate candidate fr the transplant. Services that are the subject f a clinical trial d nt meet ur Technlgy Assessment Prtcl criteria and are cnsidered investigatinal. Fr explanatin f experimental and investigatinal, please refer t the Technlgy Assessment Prtcl. It is expected that nly apprpriate and medically necessary services will be rendered. We reserve the right t cnduct prepayment and pstpayment reviews t assess the medical apprpriateness f the abve-referenced prcedures. Sme f this Prtcl may nt pertain t the patients yu prvide care t, as it may relate t prducts that are nt available in yur gegraphic area. References We are nt respnsible fr the cntinuing viability f web site addresses that may be listed in any references belw. 1. Physician Data Query. Adult Hdgkin lymphma treatment Available nline at: Last accessed Octber, Swerdlw S, Camp E, Harris N et al. WHO classificatin f tumurs f haematpietic and lymphid tissues. 4 ed. Lyn France: IARC; Isidri A, Piccaluga PP, Lsccc F et al. High-dse therapy fllwed by stem cell transplantatin in Hdgkin s lymphma: past and future. Expert Rev Hematl 2013; 6(4): Brice P. Managing relapsed and refractry Hdgkin lymphma. Br J Haematl 2008; 141(1): Schmitz N, Sureda A, Rbinsn S. Allgeneic transplantatin f hematpietic stem cells after nnmyelablative cnditining fr Hdgkin s disease: indicatins and results. Semin Oncl 2004; 31(1): Schmitz N, Dreger P, Glass B et al. Allgeneic transplantatin in lymphma: current status. Haematlgica 2007; 92(11): Mrschhauser F, Brice P, Ferme C et al. Risk-adapted salvage treatment with single r tandem autlgus stem-cell transplantatin fr first relapse/refractry Hdgkin s lymphma: results f the prspective multicenter H96 trial by the GELA/SFGM study grup. J Clin Oncl 2008; 26(36): Federic M, Bellei M, Brice P et al. High-dse therapy and autlgus stem-cell transplantatin versus cnventinal therapy fr patients with advanced Hdgkin's lymphma respnding t frnt-line therapy. J Clin Oncl 2003; 21(12): Carella AM, Bellei M, Brice P et al. High-dse therapy and autlgus stem cell transplantatin versus cnventinal therapy fr patients with advanced Hdgkin s lymphma respnding t frnt-line therapy: lng-term results. Haematlgica 2009; 94(1): Seftel M, Rubinger M. The rle f hematpietic stem cell transplantatin in advanced Hdgkin lymphma. Transfus Apher Sci 2007; 37(1): Page 5 f 6

6 11. Linch DC, Winfield D, Gldstne AH et al. Dse intensificatin with autlgus bne-marrw transplantatin in relapsed and resistant Hdgkin s disease: results f a BNLI randmized trial. Lancet 1993; 341(8852): Schmitz N, Pfistner B, Sextr M et al. Aggressive cnventinal chemtherapy cmpared with high-dse chemtherapy with autlgus haempietic stem-cell transplantatin fr relapsed chemsensitive Hdgkin s disease: a randmized trial. Lancet 2002; 359(9323): Murphy F, Sirhi B, Cunningham D. Stem cell transplantatin in Hdgkin lymphma. Expert Rev Anticancer Ther 2007; 7(3): Tdisc E, Castagna L, Sarina B et al. Reduced-intensity allgeneic transplantatin in patients with refractry r prgressive Hdgkin s disease after high-dse chemtherapy and autlgus stem cell infusin. Eur J Haematl 2007; 78(4): Smith SM, van BK, Carreras J et al. Secnd autlgus stem cell transplantatin fr relapsed lymphma after a prir autlgus transplant. Bil Bld Marrw Transplant 2008; 14(8): Sarina B, Castagna L, Farina L et al. Allgeneic transplantatin imprves the verall and prgressin-free survival f Hdgkin lymphma patients relapsing after autlgus transplantatin: a retrspective study based n the time f HLA typing and dnr availability. Bld 2010; 115(18): Peggs KS, Hunter A, Chpra R et al. Clinical evidence f a graft-versus-hdgkin s-lymphma effect after reduced-intensity allgeneic transplantatin. Lancet 2005; 365(9475): Alvarez I, Sureda A, Caballer MD et al. Nn-myelablative stem cell transplantatin is an effective therapy fr refractry r relapsed Hdgkin s lymphma: results f a Spanish prspective cperative prtcl. Bil Bld Marrw Transplant 2006; 12(2): Laprt GG. Allgeneic hematpietic cell transplantatin fr Hdgkin lymphma: a cncise review. Leuk Lymphma 2008; 49(10): Sureda A, Rbinsn S, Canals C et al. Reduced-intensity cnditining cmpared with cnventinal allgeneic stem-cell transplantatin in relapsed r refractry Hdgkin s lymphma: an analysis frm the Lymphma Wrking Party f the Eurpean Grup fr Bld and Marrw Transplantatin. J Clin Oncl 2008; 26(3): Anderlini P, Saliba R, Achlnu S et al. Fludarabine-melphalan as a preparative regimen fr reduced-intensity cnditining allgeneic stem cell transplantatin in relapsed and refractry Hdgkin's lymphma: the updated M.D. Andersn Cancer Center experience. Haematlgica 2008; 93(2): Sureda A, Canals C, Arranz R et al. Allgeneic stem cell transplantatin after reduced intensity cnditining in patients with relapsed r refractry Hdgkin's lymphma. Results f the HDR-ALLO study - a prspective clinical trial by the Grup Espanl de Linfmas/Trasplante de Medula Osea (GEL/TAMO) and the Lymphma Wrking Party f the Eurpean Grup fr Bld and Marrw Transplantatin. Haematlgica 2012; 97(2): Fung HC, Stiff P, Schriber J et al. Tandem autlgus stem cell transplantatin fr patients with primary refractry r pr risk recurrent Hdgkin lymphma. Bil Bld Marrw Transplant 2007; 13(5): Ferme C, Munier N, Divine M et al. Intensive salvage therapy with high-dse chemtherapy fr patients with advanced Hdgkin s disease in relapse r failure after initial chemtherapy: results f the Grupe d Etudes des Lymphmes de l Adulte H89 Trial. J Clin Oncl 2002; 20(2): Page 6 f 6