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The Leukemia/Bone Marrow Transplant Program of BC

Healthcare Professionals
Cancer Management Guidelines

Indolent and Transformed Lymphoma

Updated: April 2011 - currently under review

The protocols and policies for staging, management and therapy for the indolent lymphoma, including follicular lymphoma, lymphoplasmacytic and marginal zone are outlined on the BC Cancer Agency website. The scope of this management guideline will focus on the role of stem cell transplantation in the management of relapsed and refractory indolent lymphoma. 

Indolent Lymphoma

Patients who have had suboptimal response to conventional therapy (<PR) or short period of disease control (less than 1-2 years) may be considered for referral to the Leukemia/BMT Program of BC.

Patients with a good HSCT specific comorbidity score (less than 3) indicating good organ function are most likely to benefit from allo SCT.

Although much study has been done for autografting in indolent lymphoma, there has yet to be a clear survival advantage demonstrated for these patients following autografting in the modern chemoimmunotherapy regimens. Autografting is not curative for indolent lymphoma.

Therefore at the L/BMT Program of BC allografting is considered for suitable patients with these diagnoses.

The data on dose intensity in allografting for indolent lymphoma is somewhat conflicting. Selected patients may be considered for the reduced dose or non-myeloablative regimens in particular if they retain some evidence of responsiveness to standard therapies.

For lymphoplasmacytic lymphoma in particular the data would support use of the reduced intensity regimens over the myeloablative protocols.

Ideally allografting would be performed for high risk patients prior to disease transformation, as results of allo SCT post transformation are suboptimal when compared to pre-transformation. 

Transformed Lymphoma

Patients with indolent lymphoma who have transformed to higher grade disease can be referred to the Leukemia/BMT Program of BC for consideration of autografting. Prior studies by our group and others have shown that allografting has suboptimal results due to both high TRM and high relapse rates. Autografting in this group yields improved overall survival compared to allografting. There are no good studies comparing use of standard therapy to autografting in the transformed setting, however it is known that results are poor with conventional therapy, and observational studies suggest better results with high dose therapy and autografting.

For Richter’s or other transformation of CLL please see the L/BMT Program's CLL algorithm. It should be noted that allografting for transformed CLL appears to have reasonable outcomes and will be considered for suitable patientss with good risk comorbidity scores.

For lymphoma transformation involving ‘double-hit’ with both bcl-2 and c-myc translocations, i.e., Burkitt type, see the Burkitt lymphoma algorithms. These lymphomas require specialized therapy including Burkitt-type management.  They are a medical emergency and should be referred to the L/BMT Program as soon as possible.

Treatment

Algorithms

Click image to enlarge.

Indolent Lymphoma Treatment Algorithm 1 Indolent Lymphoma Treatment Algorithm 2 Transformed Lymphoma Treatment Algorithm 1

Protocols

BCCA Chemotherapy Protocols and PPOs

Publications

  1. Garnier A, Robin M, Larosa F, Golmard J-L, Gouill SL, Coiteux V, Tabrizi R, Bulabois C-E, Cacheux V, Kuentz M, Dreyfus B, Dreger P, Rio B, Moles-Moreau M-P, Bilger K, Bay J-O, Leblond V, Blaise D, Tournilhac O, Dhédin. Allogeneic hematopoietic stem cell transplantation allows long-term complete remission and curability in high-risk Waldenström’s macroglobulinemia. Results of a retrospective analysis of the Société Française de Greffe de Moelle et de Thérapie Cellulaire. Haematologica 95:950-955, 2010.
  2. Piñana JL, Martino R, Gayoso J, Sureda A, de la Serna J, Diez-Martin JL, Vazquez L, Arranz R, Tomas JF, Sampol A, Solano C, Delgado J, Sierra J, Caballero D for the GELTAMO Group. Reduced intensity conditioning HLA identical sibling donor allogeneic stem cell transplantation for patients with follicular lymphoma: long-term follow-up from two prospective multicenter trials. Haematologica 95:1176-1182, 2010.
  3. Al-Tourah A, Gill KK, Chhanabhai M, Hoskins PJ, Klasa RJ, Savage KJ, Sehn LH, Shenkier TN, Gascoyne RD, and Connors JM. Population-Based Analysis of Incidence and Outcome of Transformed Non-Hodgkin’s Lymphoma. J Clin Oncol 26:5165-5169, 2008.
  4. Armand P, Kim HT, Ho VT, ;Cutler CS, Koreth J, Antin JH, LaCasce AS, Jacobsen ED, Fisher DC, Brown JR. Canellos GP, Freedman AS, Soiffer RJ, Alyea EP. Allogeneic Transplantation with Reduced-Intensity Conditioning for Hodgkin and non-Hodgkin Lymphoma: Importance of Histology for Outcome. Biology of Blood and Marrow Transplantation 14:418-425, 2008.
  5. Ramadan KM, Connors JM, ;Al-Tourah AJ, Song KW, ;Gascoyne RD, Barnett MJ, Nevill TJ, Shepherd JD, Nantel SH, Sutherland HJ, Forrest DL, ;Hogge DE, Lavoie JC, Abou-Mourad YR, Chhanabhai M, Voss NJ, Brinkman RB, Smith CA and Toze CL. Allogeneic SCT for relapsed composite and transformed lymphoma using related and unrelated donors: long-term results. Bone Marrow Transplantation 42:601-608, 2008.
  6. Rezvani AR, Storer B, Maris M, Sorror ML, Agura E, Maziarz RT, Wade JC, Chauncey T, Forman SJ, Lange T, Shizuru J, Langston A, Pulsipher MA, Sandmaier BM, Storb R, and Maloney DG. Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation in Relapsed, Refractory, and Transformed Indolent Non-Hodgkin’s Lymphoma. J Clin Oncol 26:211-217, 2008.
  7. Ramadan KM, Connors JM, Al-Tourah A, Gascoyne RD, Song KW, Barnett MJ, Nantel SH, Nevill TJ, Shepherd JD, Sutherland HJ, Lavoie J, Forrest DL, Hogge DE, Voss NJ, Brinkman R, Abou Mourad YR, Power MM, Narayanan S, Smith CA and Toze CL. Salvage Therapy with Allogeneic Stem Cell Transplantation Results in Better Outcome for Patients with Relapsed/Refractory Follicular Lymphoma Compared to Those with Transformed Non-Hodgkin Lymphoma: A Population-Based Comparative Study. Poster Session. Blood (ASH Annual Meeting Abstracts) 112: Abstract 975, 2008.
  8. Ramadan KM, Song KW, Connors JM, Al-Tourah A, Gascoyne RD,  Barnett MJ, Nantel SH, Nevill TJ, Shepherd JD, Sutherland HJ, Lavoie J, Forrest DL, Hogge DE, Voss NJ, Brinkman R, Abou Mourad YR, Power MM, Narayanan S, Smith CA and Toze CL. Comparison of Outcome Between Refractory/Relapsed De Novo Diffuse Large B-Cell and Transformed Lymphoma Using Related and Unrelated Allogeneic Hematopoietic SCT. Poster Session. Blood (ASH Annual Meeting Abstracts) 112: Abstract 2173, 2008.
  9. Montoto S, Davies AJ, Matthews J, Calaminici M, Norton AJ, Amess J, Vinnicombe S, Waters R, Rohatiner AZS, and Lister TA. Risk and Clinical Implications of Transformation of Follicular Lymphoma to Diffuse Large B-Cell Lymphoma. J Clin Oncol 25:2426-2433, 2007.
  10. Toze CL, Barnett MJ, Connors JM, Gascoyne RD, Voss NJ, Nantel SH, Nevill TJ, Shepherd JD, Sutherland HJ, Lavoie JC, Forrest DL, Song KW and Hogge DE. Long-term disease-free survival of patients with advanced follicular lymphoma after allogeneic bone marrow transplantation. British Journal of Haematology 127: 311-321, 2004.
  11. Hosing C, Saliba RM, McLaughlin P, Andersson B, Rodriguez MA, Fayad L, Cabanillas F, Champlin ;RE & Khouri IF. Long-term results favor allogeneic over autologous hematopoietic stem cell transplantation in patients with refractory or recurrent indolent non-Hodgkin’s lymphoma. Annals of Oncology 14: 737-744, 2003.

 

The information contained in these guidelines is a statement of consensus of Leukemia/BMT Program of BC professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patientís care or treatment. Use of these guidelines and documents is at your own risk and is subject to the Leukemia/BMT Program of BCís terms of use available at Terms of Use.

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