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 Zambia HIV National Guidelines
 


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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS
 

 

 

Diagnosis>Malignancies>
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Lymphoma, Non-Hodgkins (NHL)

Mark Levis, M.D., Ph.D. and Nina Wagner, M.D.
08-17-2009

Zambia Specific Information

  • Little specific information available regarding risk of lymphoma in HIV+ patients in sub-Saharan Africa. Recent review from University Teaching Hospital in Lusaka found that NHL ranked #5 (accounting for 6.3% of malignancies) with the top 4 in order being KS, ocular cancer, soft tissue sarcoma and prostate cancer.
  • African data demonstrate increased risk for NHL but not Hodgkin's lymphoma
  • Burkitt's lymphoma due to EBV remains a common childhood tumor regardless of HIV status.

REFERENCES

Zambia Information Author: Paul Auwaerter, M.D.

PATHOGENS

CLINICAL

  • Late manifestation of disease, most often associated with CD4 <100, though can occur at any CD4 count.
  • No obvious environmental factors, but possible genetic predisposition: more common in men and in those with SDF-1 mutations.
  • Incidence of all AIDS-related lymphomas (ARL) has declined since HAART, but decline less dramatic for lymphoma than for OIs, making it a common AIDS-defining illness.
  • Several different variants of ARL: diffuse large B-cell lymphoma (DLBCL), PCNSL, immunoblastic/plasmablastic lymphoma, Burkitt's or Burkitt's-like lymphoma, and primary effusion lymphoma (PEL,body cavity lymphoma).
  • 2 subtypes almost uniquely associated with HIV are primary effusion lymphoma and plasmablastic lymphoma of the oropharynx.
  • EBV infection of the tumor (and EBV DNA in CSF) predictive of CNS metastasis.
  • ARLs typically present at advanced stage, often with extranodal and CNS involvement.

DIAGNOSIS

  • When possible, obtain Bx of node or affected organ. FNA is NOT desired mode of Dx, although it can often be used when Bx is not feasible.
  • Immunophenotyping of paraffin block or flow cytometric analysis of cell surface markers (CD3, CD5, CD10, CD15, CD20, CD30, Ki-67) in combination with molecular studies (EBV or HHV-8, cytogenetics, FISH).
  • Staging workup should include chest/abdomen/pelvic CT, bone marrow biopsy and aspirate, LP, CBC, LDH and complete chemistries. Brain MRI with gadolinium should be considered in most cases, and stool guaiac in any patient with abdominal involvement.
  • Role of PET in AIDS-related lymphoma remains unclear, though frequently obtained.

TREATMENT

Prognosis

  • International Prognostic Index (IPI) scores useful in predicting outcome. Poor risk features: age > 60, reduced performance status, elevated LDH, advanced stage (common in ARL), and more than one site of extra-nodal involvement.
General Considerations

  • Most chemotherapy regimens safe to give with HAART, but overlapping toxicity is a problem for some agents. Etoposide, vincristine, cyclophosphamide, and prednisone serum levels may be increased with PI co-administration. Withholding HAART during dose-adjusted EPOCH was not detrimental (VL did not increase). No standard of care established.
  • AZT can prolong or exacerbate chemotherapy-induced neutropenia. ddI and/or d4T can increase risk of neuropathy
  • G-CSF routinely used during chemotherapy to shorten duration of neutropenia.
  • Gastric or intestinal DLBCL is well-described presentation of ARL associated with an increased risk GI bleeding or perforation during chemotherapy (compared with GI DLBCL in non-AIDS population). Such pts often made NPO and placed on parenteral nutrition during 1st cycle of chemotherapy.
  • Rituximab (anti-CD20 monoclonal antibody) routinely used in ARL despite initial concerns of increased infectious complications.
  • In post-HAART era, survival following treatment for ARL approaching that for lymphoma in the non-AIDS population.
Regimens

  • Effective regimens include R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-EPOCH (rituximab, etoposide, vincristine, cyclophosphamide, doxorubicin given by continuous infusion with prednisone). Reported complete remission rates are 80% or more, with 2 year survival of >50%.
  • Intrathecal chemotherapy with methotrexate or cytarabine recommended if BM involvement, Burkitt's histology, or EBV +.
  • Burkitt lymphoma generally requires more intensive regimens, such as hyper-CVAD.
  • High-dose therapy with autologous stem cell transplantation is increasingly being used for relapsed or refractory disease.

REFERENCES

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