British Journal of Haematology, 1999, 105, 795–798
SHORT REPORT
Syngeneic stem cell transplantation for HIV-related lymphoma P. C A M P B E L L , H. I L A N D , J. G I B S O N A N D D. J O S H UA Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, N.S.W., Australia Received 7 October 1998; accepted for publication 26 February 1999
Summary. The treatment of human immunodeficiency virus (HIV)-related lymphoma is beset by a number of therapeutic limitations. High-dose chemotherapy followed by peripheral blood stem cell transplantation (PBSCT) for relapsed disease is one option, but may be compromised by unacceptable treatment-related morbidity and mortality. We describe an HIV-positive male with relapsed immunoblastic non-Hodgkin’s lymphoma (NHL) who successfully received salvage chemotherapy followed by a syngeneic PBSCT from his HIV-
negative (hepatitis C positive) brother. At 15 months posttransplant he remains in complete remission with low-level HIV viral load, an improved CD4 lymphocyte count and absent anti-hepatitis C antibodies. We believe selected patients with relapsed HIV-related NHL should be considered for high-dose therapy.
The incidence of non-Hodgkin’s lymphoma (NHL) is markedly increased in HIV-infected individuals and is characterized by aggressive disease histology, high probability of disseminated extranodal disease at presentation, and lower response rates to chemotherapy when compared with a non-HIV population. In addition to HIV-related prognostic factors such as CD4 count, performance status, age and serum LDH level predict for poor prognosis (Sandler & Kaplan, 1996; Vaccher et al, 1996). Administration of effective cytoreductive therapy is often compromised by poor haemopoietic reserve, the risk of intercurrent opportunistic infection and worsening immunosuppression. As a consequence, aggressive chemotherapy approaches have been associated with reduced survival, although recent use of haemopoietic growth factors and modified chemotherapy schedules have the potential to reduce treatment-related morbidity and mortality. High-dose chemotherapy followed by autologous bone marrow transplantation is now considered standard practice for many patients with chemotherapy-sensitive NHL in relapse (Philip et al, 1995). The use of haemopoietic growthfactor-mobilized peripheral blood stem cells (PBSCs) instead of bone marrow has significantly shortened the time to engraftment following high-dose therapy and contributed to dramatic reductions in transplant-related morbidity and mortality (Schmitz et al, 1996). These improvements in
engraftment kinetics may also make such therapies more applicable to patients with HIV-related NHL. We describe an HIV-positive male with relapsed NHL succesfully treated with continuous infusion salvage chemotherapy followed by syngeneic PBSCT from his HIV-negative, hepatitis C positive, identical twin brother. At 15 months following transplantation he remains in complete remission with low-level viraemia on RT-PCR, falling HIV antibodies, a slow decrease in CD4 count, and stable levels of hepatitis C viral RNA on RT-PCR.
Correspondence: Dr H. J. Iland, The Kanematsu Laboratories, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia. e-mail:
[email protected]. q 1999 Blackwell Science Ltd
Keywords: HIV, lymphoma, syngeneic, transplant, antiretrovirals.
CASE REPORT A 33-year-old homosexual male was found to be HIVpositive on routine testing in 1984 with a CD4 count of 497 × 106/l. In 1995 he presented with left ocular pain due to an orbital mass. At that time he was on dual antiretroviral therapy (Lamivudine, Stavudine; CD4 count 200 × 106/l) and had experienced no prior AIDS-defining ilnesses. Physical examination revealed an obvious left orbital swelling at the superior medial angle with no other evidence of palpable disease. Biopsy of the left orbital mass revealed a diffuse large cell immunoblastic non-Hodgkin’s lymphoma (IgGk positive and CD3 negative). All microbiological cultures were sterile. His full blood count was; haemoglogin 15·3 g/dl, white cell count 4·2 × 109/l, platelets 290 × 109/l, mean corpuscular volume 115·5 fl, neutrophils 1·43 × 109/l. His serum calcium was normal, lactate dehydrogenase marginally elevated at 236 U/l (normal range 0–220 U/l) and no
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Fig 1. Whole-body gallium scans demonstrating sites of active lymphoma: (a) at diagnosis; (b) following six cycles of CHOP; (c) at relapse; (d) posttransplant (see text for details).
paraprotein detected on serum protein electrophoresis. Staging investigations including CT and gallium scanning demonstrated multiple areas of bony destruction and associated soft tissue masses involving the left orbit, right occipital bone, bilateral lower ribs and lumbar spine (Fig 1a). Lumbar puncture, bone marrow aspirate and trephine showed no evidence of lymphomatous infiltration. He received six cycles of CHOP chemotherapy (cyclophosphamide 750 mg/m2 day 1 i.v., doxorubicin 50 mg/m2 day 1 i.v., vincristine 1·5 mg day 1 i.v. and prednisone 100 mg orally days 1–5) with intermittent granulocyte-colony stimulating factor (G-CSF) support. Therapy was well tolerated, not associated with infectious complications and his anti-retroviral therapy required only minor modification because of an increase in HIV viral load detected by PCR monitoring (Chiron bDNA assay) (Table I). Restaging investigations performed after six cycles of treatment suggested complete remission. CT scans demonstrated regression of the skeletal lesions with residual lytic lesions surrounded by sclerotic bands on skeletal survey suggestive of healing. Gallium scanning confirmed complete disease resolution. Proximal humoral uptake was thought to represent ‘marrow reaction’ (Fig 1b).
Six months following completion of his chemotherapy he represented with pain and weakness in his right arm due to recurrence in his right posterolateral first rib and brachial plexus involvement. There were no other areas of recurrence on restaging and he was treated with local radiotherapy (40 Gy over 20 fractions). Six weeks following completion of his radiotherapy (14 months following diagnosis) he relapsed at the right iliac bone, angle of the right mandible and the upper left forearm (Fig 1c). Fine-needle aspiration of the right buttock mass confirmed the original histology. There was no evidence of bone marrow involvement on restaging. He received two courses of CDE chemotherapy, a 4 d continuous i.v. infusion schedule of cyclophosphamide (800 mg/m2), doxorubicin (50 mg/m2) and etoposide (240 mg/m2) with G-CSF support (Sparano et al, 1996). The CDE therapy was well tolerated with no infectious complications and only a minor increase in viral load coinciding with a reduction in his anti-retroviral therapy (Table I). Clinically there was complete resolution of the palpable disease in the right buttock and the left forearm. Repeat scanning revealed regression of bony lesions and a previously-described area of persistent gallium uptake in
q 1999 Blackwell Science Ltd, British Journal of Haematology 105: 795–798
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Table I. Results of HIV viral loads and CD4 lymphocyte counts before and after high-dose therapy.
Time to PBSCT (months)
HIV viral load (copies/ml)
CD4 count (×106/l)
Hepatitis C antibodies
HCV RNA (copies/ml)
Chemotherapy and anti-retroviral status
¹18 ¹13 ¹10 ¹6 ¹3 ¹1 þ1·5 þ3 þ5 þ8 þ13
NA NA 63253
