Derangements of immunological proteins in HIV-associated diffuse large B-cell lymphoma: the frequency and prognostic impact.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy of B-cells frequently encountered among people living with HIV. Immunological abnormalities are common in immunocompetent individuals with DLBCL, and are often associated with poorer outcomes. Currently, data on derangements of immunological proteins, such as cytokines and acute phase reactants, and their impact on outcomes in HIV-associated DLBCL (HIV-DLBCL) is lacking. This study assessed the levels and prognostic relevance of interleukin (IL)-6, IL-10 and Transforming Growth Factor Beta (TGFß), the acute phase proteins C-reactive protein (CRP) and ferritin; serum free light chains (SFLC) (elevation of which reflects a prolonged pro-inflammatory state); and the activity of the immunosuppressive enzyme Indoleamine 2,3-dioxygenase (IDO)in South African patients with DLBCL. Methods: Seventy-six patients with incident DLBCL were enrolled, and peripheral blood IL-6, IL-10, TGFß, SFLC and IDO-activity measured in selected patients. Additional clinical and laboratory findings (including ferritin and CRP) were recorded from the hospital records. Results: Sixty-one (80.3%) of the included patients were people living with HIV (median CD4-count = 148 cells/ul), and survival rates were poor (12-month survival rate 30.0%). The majority of the immunological proteins, except for TGFß and ferritin, were significantly higher among the people living with HIV. Elevation of IL-6, SFLC and IDO-activity were not associated with survival in HIV-DLBCL, while raised IL-10, CRP, ferritin and TGFß were. On multivariate analysis, immunological proteins associated with survival independently from the International Prognostic Index (IPI) included TGFß, ferritin and IL-10. Conclusion: Derangements of immunological proteins are common in HIV-DLBCL, and have a differential association with survival compared to that reported elsewhere. Elevation of TGFß, IL-10 and ferritin were associated with survival independently from the IPI. In view of the poor survival rates in this cohort, investigation of the directed targeting of these cytokines would be of interest in our setting.

The prognostic impact of monocyte fluorescence, immunosuppressive monocytes and peripheral blood immune cell numbers in HIV-associated Diffuse Large B-cell Lymphoma.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a high grade non-Hodgkin lymphoma which is common among immunodeficient people. Derangements of peripheral blood immune cells have been described to have a prognostic impact in DLBCL in high income countries, including a monocytosis, the ratios of lymphocytes to both monocytes (L:M) and neutrophils (N:L), as well as the numbers of regulatory T-cells (Tregs) and immunosuppressive monocytes (HLA-DRlow monos). To date, the impact of these variables has not been assessed in the setting of HIV-associated DLBCL (HIV-DLBCL), which is among the most common malignancies seen in people living with HIV. In this study, we assessed these factors in a cohort of South African patients with DLBCL and a high HIV-seropositivity-rate. In addition, we evaluated the prognostic value of monocyte activation (as reflected by monocyte fluorescence (MO-Y) on a Sysmex haematology analyser). This parameter has to date not been assessed in the setting of DLBCL. METHODS: A full blood count and differential count as well as flow cytometry for HLA-DRlow monocyte and Treg enumeration were performed in patients with incident DLBCL referred to the Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa between November 2019 and May 2022. Additional clinical and laboratory data were recorded from the patient charts and laboratory information system. RESULTS: Seventy-six patients were included, of whom 81.3% were people living with HIV with a median CD4 count of 148 cells/ul. Most patients had advanced stage disease (74.8%) and were predominantly treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy (without Rituximab). At a median follow-up period of 19 months, the median survival time was 3.5 months, with a 12-month survival rate of 27.0%. All of the immune-cell-related variables (with the exception of the CD4 count) were similar between the people living with HIV and the HIV-negative individuals. In contrast to previous studies, a high monocyte count, the L:M and increased numbers of HLA-DRlow monocytes were not significantly associated with survival in HIV-DLBCL, while a neutrophilia (>8 x 109/L), the N:L (>6:1), high numbers of Tregs (≥5.17% of CD4s) and lymphopenia (<1.3 x 109/L) were. In addition, increased monocyte fluorescence (MO-Y >115.5) was associated with superior outcomes, which we speculate to reflect a more robust antitumour immune response among individuals with high levels of monocyte activation. On Cox Proportional hazard analysis, immune-cell factors independently associated with survival included a CD4 count <150 cells/ul and a neutrophilia. CONCLUSION: The monocyte count, L:M and the number of HLA-DRlow monos are not strong prognostic indicators in HIV-DLBCL, while a low CD4 count and neutrophilia are. Elevation of the MO-Y shows some promise as a potential biomarker of antitumour immunity; further study in this regard would be of interest.

Prevalence of Monoclonal Gammopathy of Undetermined Significance in Black South African Men.

BACKGROUND: Both multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance (MGUS), occur twice as often within Black compared with White populations, suggesting that racial disparities lie within the development of MGUS. Nonetheless, MGUS has been studied mainly in White cohorts; the study that first described the natural history of MGUS was conducted in 97.3% White Olmsted County, Minnesota. METHODS: We determined the prevalence of MGUS among 386 Black South African (SA) men >30 years at Chris Hani Baragwanath Hospital in Johannesburg. We conducted serum protein electrophoresis and free light chain quantification to define MGUS by the same criteria as the Olmsted County studies. We also investigated the association between MGUS and various clinical factors, including human immunodeficiency virus (HIV) infection and smoking. RESULTS: We found the prevalence of MGUS to be 8.03% [95% confidence interval (CI), 5.32-10.74], nearly 1.6-fold higher than in the White Olmsted County male population. In a univariable logistic regression model, MGUS was associated with HIV status (OR, 2.39; 95% CI, 0.95-5.49), but in an adjusted model that included body mass index and cigarette use, the association was not statistically significant. Those who were current (vs. never) cigarette smokers were more likely to have MGUS in both univariable (OR, 5.60; 95% CI, 2.16-17.42) and multivariable models (OR, 4.49; 95% CI, 1.63-14.56). CONCLUSIONS: The prevalence of MGUS in Black SA men is substantially higher than in White populations and may be associated with HIV status and cigarette use. IMPACT: Racial disparities in MGUS exist and may be associated with potentially modifiable risk factors.

Significance of lymph node fine needle aspiration for the diagnosis of HIV-associated lymphoma in a low-resource setting.

OBJECTIVE: Fine needle aspiration (FNA) is an early step in the work-up of lymphadenopathy in people with HIV (PWH). We set out to characterize the FNA cytology in PWH and report on the time to lymphoma diagnosis through the FNA clinics in the public healthcare system in Johannesburg, South Africa. DESIGN: Retrospective review of laboratory database. METHODS: A retrospective chart review of patients undergoing FNA through the department of cytopathology at the National Health Laboratory Service (NHLS) was undertaken. Results of FNAs performed between March and May 2018 were reviewed. Medical record chart abstraction included general demographics, HIV status, site and results of FNA, prior history of malignancy and other laboratory data. RESULTS: Five hundred and thirty-nine lymph node FNAs were performed on PWH. Pathological findings included tuberculosis 47% (252), inadequate sampling 14% (75), reactive adenopathy 13% (71), benign disease 12% (63), suspicious for lymphoproliferative neoplasm 8% (45), other malignancy 4% (21) and inflammation 2% ( n  = 12). Only 53% (24) of lymphomas were confirmed by biopsy. Those not confirmed had a high mortality (57%) and loss to follow-up rate (29%) over the following year. The median diagnostic interval exceeded 8 weeks from time of FNA to lymphoma diagnosis. CONCLUSION: FNA is an important screening modality in this high HIV and tuberculosis (TB) burden region. Patients with cytology suggestive for lymphoma, but without biopsy confirmation, have a high mortality rate suggesting undiagnosed lymphoma. A better understanding of the barriers to appropriate diagnostic triage for lymphoma is needed.

HIV-associated DLBCL: Clinicopathological factors including dual-colour chromogenic in situ hybridisation to assess MYC gene copies.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) comprises up to 43% of non-Hodgkin lymphomas in South Africa due to the high seroprevalence of human immunodeficiency virus (HIV) infection in the southern African region. We explored the prognostic influence of an array of clinicopathological factors, including MYC gene copy numbers, within HIV-associated DLBCL. METHODS: The retrospective inclusion of 123 tumours was followed by c-MYC immunohistochemistry and dual-colour MYC and centromere 8 (CEN8) chromogenic in situ hybridisation on formalin-fixed paraffin-embedded sections. Clinicopathological data were collected, interpreted and analysed. RESULTS: HIV seropositive patients comprised 81% (93/115), mean age 42 (SD 10.8) years, with 55% males, HIV negative patients comprised 19% (22/115), mean age 57 (SD 16.7) years (p = 0.001), with 59% males and the HIV status was unknown for 8 patients. The median CD4 count was 162 (IQR 215) cells/mm3, 33% of patients presented with CD4 counts <100 cells/mm3 and the median viral load was 217 (IQR 182 981) copies/mL. There was advanced stage at presentation (i.e., III-IV, 87%), with Ki-67 proliferation indices ≥90% in 85%- and c-MYC expression (i.e., ≥40%) in 58% of tumours. Double expression of c-MYC and BCL2 was associated with a non-germinal center immunophenotype (p < 0.01). Low-level increase of MYC gene copy numbers and MYC rearrangements occurred in 57% and 12%, respectively. C8 polysomy, MYC gene clusters and concurrent MYC rearrangement/increased MYC gene copies were also detected. Inferior median overall survival (OS) occurred when the CD4 counts were <100 cells/mm3 (149 days 95% CI 44-254, p 0,04) and when IPI scores were 3-5 [155 days (95% CI 37-273), p = 0.01]. Concomitant infections negatively impacted the survival outcome, multivariate regression analysis (HR 4.01, 95% CI 1.86-12.20, p = 0.02). CONCLUSION: c-MYC protein expression, low-level increase in MYC gene copy numbers, rearrangement, C8 polysomy, MYC gene clusters and concurrent MYC rearrangement/low-level gains are present in HIV+ DLBCL. CD4 counts < 100 cells/mm3, IPI scores 3-5 and concomitant infections negatively impact the survival outcome.

Hyperlipidemic myeloma, a rare form of acquired dysbetalipoproteinemia, in an HIV seropositive African female.

Dysbetalipoproteinemia (DBL) is an uncommon condition characterized by a mixed hyperlipidemia due to accumulation of remnant lipoproteins and is highly atherogenic. Typically, DBL is an autosomal recessive condition requiring an additional metabolic stress with reduced apolipoprotein E (apoE) function. However, DBL is also described in patients with multiple myeloma without the characteristic apoE2/E2 mutation seen in familial DBL. Although the underlying pathogenesis in these cases is not fully characterized, it is thought to occur due to interference with apoE function by antibodies produced from clonal plasma cells. Such cases are referred to as hyperlipidemic myeloma (HLM) and have rarely been described in the literature. To our knowledge there is no prior description of HLM in HIV positive patients in Africa. We describe a case of HLM in an African woman with underlying HIV infection who presented with phenotypic and biochemical features of DBL that responded poorly to lipid lowering therapy.

Feasibility of Cell-Free DNA Collection and Clonal Immunoglobulin Sequencing in South African Patients With HIV-Associated Lymphoma.

PURPOSE: Diagnosis of AIDS lymphoma in low-resource settings, like South Africa, is often delayed, leaving patients with limited treatment options. In tuberculosis (TB) endemic regions, overlapping signs and symptoms often lead to diagnostic delays. Assessment of plasma cell-free DNA (cfDNA) by next-generation sequencing (NGS) may expedite the diagnosis of lymphoma but requires high-quality cfDNA. METHODS: People living with HIV with newly diagnosed aggressive B-cell lymphoma and those with newly diagnosed TB seeking care at Chris Hani Baragwanath Academic Hospital and its surrounding clinics, in Soweto, South Africa, were enrolled in this study. Each participant provided a whole blood specimen collected in cell-stabilizing tubes. Quantity and quality of plasma cfDNA were assessed. NGS of the immunoglobulin heavy chain was performed. RESULTS: Nine HIV+ patients with untreated lymphoma and eight HIV+ patients with TB, but without lymphoma, were enrolled. All cfDNA quantity and quality metrics were similar between the two groups, except that cfDNA accounted for a larger fraction of recovered plasma DNA in patients with lymphoma. The concentration of cfDNA in plasma also trended higher in patients with lymphoma. NGS of immunoglobulin heavy chain showed robust amplification of DNA, with large amplicons (> 250 bp) being more readily detected in patients with lymphoma. Clonal sequences were detected in five of nine patients with lymphoma, and none of the patients with TB. CONCLUSION: This proof-of-principle study demonstrates that whole blood collected for cfDNA in a low-resource setting is suitable for sophisticated sequencing analyses, including clonal immunoglobulin NGS. The detection of clonal sequences in more than half of patients with lymphoma shows promise as a diagnostic marker that may be explored in future studies.

MYC status in HIV-associated plasmablastic lymphoma: dual-colour CISH, FISH and immunohistochemistry.

AIMS: We utilised chromogenic and fluorescence in-situ hybridisation (CISH and FISH) to evaluate MYC gene copy numbers and rearrangements within HIV-associated plasmablastic lymphomas (PBLs). Thereafter, clinicopathological features were explored retrospectively. METHODS AND RESULTS: Sixty-seven (n = 67) patients were included and the HIV seropositive status was confirmed in 98% (63 of 64) with a median viral load of 55 587 (IQR 273 582) copies/ml and median CD4 count of 170 (IQR 249) cells/µl. The mean age was 41 ± 10.1 years and females comprised 54%. PBL was documented predominantly at extra-oronasal topographic regions. Starry-sky (SS) appearance was evident in 33% in association with monomorphic morphology (P-value 0.02). c-MYC protein was expressed in 81% and latent EBV infection was detected in 90%. EBER ISH-positive status and MYC rearrangement occurred in 67% of HIV PBL. MYC aberrations included MYC rearrangement (70%), low-level increase in MYC gene copy numbers (43%), concurrent MYC rearrangement and increased MYC gene copy numbers (49%) as well as low-level chromosome 8 polysomy (6%). MYC aberrations in HIV PBLs were significantly associated with SS appearance (P -0.01), monomorphic morphology (P - 0.03), c-MYC protein expression ≥40% (P - 0.03) and mortality (P - 0.03). There was advanced stage (Ann Arbor III/IV) at presentation (77%) and the median overall survival for HIV PBL was 75 days (95% CI 14-136). CONCLUSION: Majority of the HIV-associated PBL tumours harbour MYC aberrations. Due to the persistently inferior survival outcome of HIV-associated PBL in the era of antiviral treatment, targeted and/or intensified therapy of oncogenic MYC may need to be explored in future.

Rituximab biosimilar RTXM83 versus reference rituximab in combination with CHOP as first-line treatment for diffuse large B-cell lymphoma: a randomized, double-blind study.

This multicenter, double-blind, randomized study compared the efficacy, pharmacokinetics (PKs)/pharmacodynamics (PDs), safety and immunogenicity profile of RTXM83 vs. reference rituximab (R-rituximab), both with CHOP, as first-line treatment of diffuse large B-cell lymphoma (DLBCL). A total of 272 patients <65 years of age, with good prognosis (136 per arm) were randomized (1:1) to receive six cycles of either RTXM83 or R-rituximab. The primary efficacy endpoint was achieved (overall response rate of 83.6% for RTXM83 and 82.9% for R-rituximab) with a difference 0.7% between arms (95%CI: [-8.77% to 10.17%]) fulfilling the predefined non-inferiority margin (-13%). Similar number of patients reported at least one adverse event (AE) (131 per arm) or one serious AE (47 with RTXM83 and 45 with R-rituximab). Anti-drug antibody development was comparable between the arms. PK/PD secondary endpoint results support similarity between the compounds. RTXM83 exhibits non-inferior efficacy and similar safety/immunogenicity to R-rituximab, being an accessible alternative for the treatment of patients with previously untreated DLBCL.

Worldwide Network for Blood and Marrow Transplantation Recommendations for Establishing a Hematopoietic Stem Cell Transplantation Program in Countries with Limited Resources, Part II: Clinical, Technical, and Socioeconomic Considerations.

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. Although this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state-of-the-art treatments, including transplantation, by providing financial, technological, legal, ethical, and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population and potentially provide long-term cost savings by circumventing the need for their citizens to seek care abroad. The costs of establishing an HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. In addition, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT, and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation for establishing HSCT programs, with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in resource-constrained settings.

An Expanded Spectrum of High-Grade B-Cell Non-Hodgkin Lymphomas Involving the Cervicovaginal Region.

The uterine cervix and vaginal regions are infrequently infiltrated by lymphoma. Involvement of these topographic regions may constitute primary disease or more commonly represent a manifestation of systemic lymphomatous disease. Herein, we report an expanded spectrum of high-grade B-cell non-Hodgkin lymphomas comprising plasmablastic lymphoma (with and without plasmacytic differentiation), ALK-positive large B-cell lymphoma, and diffuse large B-cell lymphoma which involved the uterine cervix and/or vagina of 6 patients at initial diagnosis. These tumors clinically mimicked carcinoma and developed predominantly, but not exclusively, in the setting of human immunodeficiency virus infection.

Hepatosplenic T-cell lymphoma: A case series.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of Non-Hodgkin Lymphoma (NHL), grouped under the mature or peripheral T-cell lymphomas. It is characterised by extranodal infiltration and proliferation of malignant T-cells within the sinusoids of the liver, sinuses and red pulp of the spleen, and the bone marrow. The tumour cells express CD2 and CD3, but are CD4, CD5 and CD8 negative and express a clonally restricted gamma-delta (or less commonly alpha-beta) T-cell receptor. The disease has an aggressive clinical course associated with a poor prognosis. We highlight and report three patients from South Africa with HSTCL, all of whom had hepatosplenomegaly and cytopaenias, and despite being HIV seronegative and immunocompetent, had a poor outcome, with a mean survival of 7.5 months in the two evaluable patients. This rare entity has not previously been reported from South Africa and as yet needs to be adequately characterised in a population where lymphoma is the most common haematological malignancy in adults, and where approximately two thirds of the adult lymphoma population are HIV seropositive.

Classical Hodgkin Lymphoma involving the central nervous system (brain) - an unusual presentation.

KEY CLINICAL MESSAGE: Intracranial Hodgkin lymphoma (HL) is considered so atypical that an intracranial space-occupying lesion in a patient with known HL should be thoroughly investigated to rule out a second disease process.

Human immunodeficiency virus infection and chronic myeloid leukemia.

CML (chronic myeloid leukaemia) in association with HIV (human immunodeficiency virus) infection (HIV-CML) is rarely described and is likely to be coincidental. The natural history and behaviour of HIV-CML is different, being more atypical and aggressive. Both conditions, and their respective treatments may cause myelosuppression. Concurrent treatment with cART (combination antiretroviral therapy) and the tyrosine kinase inhibitors (TKI's) can result in appropriate control of CML and HIV infection, as well as long term survival. However, drug interactions between ARV's and TKI's may require adjustment of treatment.

A review of the use of blood and blood products in HIV-infected patients.

Despite numerous publications on the appropriate use of blood and blood products, few specifically consider the role of transfusion in the management of HIV. This review is a synthesis of conditions encountered in the management of HIV-infected patients where the transfusion of blood or blood products may be indicated. A consistent message emerging from the review is that the principles of transfusion medicine do not differ between HIV-negative and -positive patients. The aim of the review is to provide clinicians with a practical and succinct overview of the haematological abnormalities and clinical circumstances most commonly encountered in the HIV setting, while focusing on the rational and appropriate use of blood and blood products for HIV patients. Important ethical considerations in dealing with both the collection and transfusion blood and blood products in the HIV era have also been addressed.

Human Immunodeficiency Virus Infection and Hodgkin's Lymphoma in South Africa: An Emerging Problem.

Hodgkin's lymphoma (HL) occurs with increasing frequency in human-immunodeficiency-virus-(HIV-) infected individuals. The natural history and behaviour of HIV-HL is different, being more atypical and aggressive. The association between HIV and HL appears to be primarily EBV driven. HAART use does not significantly impact on the incidence of HL. Indeed, the risk of HL has increased in the post-HAART era. However, the advent of HAART has brought renewed hope, allowing standard therapeutic options to be used more optimally, with better treatment outcomes. Despite the renewed optimism, the overall survival of HIV-HL patients remains less favourable than that in HIV-seronegative patients. This is particularly true in sub-Saharan Africa, where there is a significant burden of HIV/AIDS and where more than half the patients are HAART naive at diagnosis of HL. The similarities and differences of a South African cohort of HIV-HL are presented in this paper.

Fludarabine-based conditioning chemotherapy for allogeneic hematopoietic stem cell transplantation in acquired severe aplastic anemia.

Thirty-eight patients who met the diagnostic criteria for severe aplastic anemia underwent allogeneic hematopoietic stem cell transplantation (HSCT). The median patient age was 20 years (range, 14-36 years). Twenty-four patients were treatment-naïve, 11 had failed one or more previous courses of immunosuppressive therapy, and 3 had failed a previous HSCT. The conditioning regimen included fludarabine 30 mg/m(2)/day for 3 days (days -9, -8, and -7) and cyclophosphamide 50 mg/kg/day for 4 days (days -5, -4, -3, and -2). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-course methotrexate. All patients underwent transplantation with unmanipulated bone marrow as the stem cell source. The median total nucleated cell (TNC) dose was 2.43 × 10(8)/kg (range, 0.60-6.7 × 10(8)/ kg). The conditioning regimen was well tolerated, with minimal treatment-related mortality. Engraftment was observed in all patients after transplantation; the median time to engraftment of neutrophils and platelets was 18 and 23 days, respectively. Twenty-five of the 27 patients with available chimeric studies at day 180 maintained donor chimerism. Acute GVHD grade ≥II was diagnosed in 4 patients (11%). Extensive chronic GVHD was observed in 8 patients (25%) who survived beyond day +100, at a median observation time of 43 months. Graft rejection with relapse of aplais was observed in one patient. The overall survival (OS) for the whole group was 79%. A trend toward improved OS was observed in the treatment-naïve patients (83% vs 71%), but this was statistically insignificant (P = .384). The fludarabine-based conditioning regimen used in this study with relatively young cohort of patients was well tolerated, with a low rate of rejection and treatment outcomes comparable to those seen in other, more intense and potentially more toxic conditioning regimens. Our results await validation in a larger study, optimally in a randomized controlled manner.

High efficacy and low toxicity of short-course oral valganciclovir as pre-emptive therapy for hematopoietic stem cell transplant cytomegalovirus infection.

BACKGROUND: Cytomegalovirus (CMV) infection is a major infectious complication post-allogeneic hematopoietic stem cell transplantation (HSCT). CMV seropositivity in Eastern Mediterranean and certain Asian countries is reported to be close to 100%; hence, the need for effective pre-emptive treatment strategy that has low toxicity. Valganciclovir (VGC) is a prodrug of ganciclovir with high bioavailability. PATIENTS AND METHODS: HSCT patients with documented CMV infection (as defined by positive CMV antigenemia) were treated as outpatients with VGC at a starting dose of 900 mg twice daily for 1 week. Those who were antigenemia negative after one week received 900 mg once daily for another week and treatment was subsequently discontinued. Those who were positive after one week of therapy continued on the twice-daily treatment schedule for another week and changed to a daily schedule once they converted to antigenemia negativity. RESULTS: From January 2004 to December 2007, 47 HSCT patients received preemptive treatment with VGC for 61 episodes of CMV infection. The antigenemia range was 1 to 700 infected cells/slide. Complete responses were observed in 92% and 97% after the 1st and 2nd week of treatment, respectively. Three percent of the episodes were considered refractory, requiring alternative therapy. No CMV disease was observed in this cohort. CONCLUSION: Neutropenia was the main observed toxicity, requiring granulocyte-colony stimulating factor in 8 episodes. Outpatient treatment of CMV infection with "short-course oral VGC" given as a one-week twice-daily treatment and one week once daily maintenance is a highly effective therapy with minimal toxicity. These results require validation in a larger, randomized study.