Infection with the human immunodeficiency virus type 1 (HIV-1) requires the presence of a CD4 receptor and a chemokine receptor, principally chemokine receptor 5 (CCR5). Homozygosity for a 32-bp deletion in the CCR5 allele provides resistance against HIV-1 acquisition. We transplanted stem cells from a donor who was homozygous for CCR5 delta32 in a patient with acute myeloid leukemia and HIV-1 infection. The patient remained without viral rebound 20 months after transplantation and discontinuation of antiretroviral therapy. This outcome demonstrates the critical role CCR5 plays in maintaining HIV-1 infection.

Changes of the peripheral blood cell count in patients with AN is a frequent observation but the peripheral blood cell count cannot predict the severity of bone marrow atrophy. All hematological and morphological alterations disappear completely and rapidly after sufficient refeeding.

Human cytomegalovirus (CMV) is a major cause of death after transplantation. The frequency of pp65-specific T cells was examined in 38 HLA-A2 þ stem cell recipients during the first year after transplantation. Patients were divided into four groups based on donor/recipientand dÀ/rÀ (n ¼ 5). Peripheral blood mononuclear cells were stimulated with the CMVpp65 peptide NLVPMVATV, and the specific T-cell frequency was assessed by interferon gamma (IFN-c) ELISPOT assay. Responding T cells were characterized by flow cytometry revealing a terminal differentiated effector phenotype. Surveillance of CMV infection was carried out by realtime polymerase chain reaction (n ¼ 26) or immunofluorescence (n ¼ 12). Infection was present in 7/9 dÀ/r þ high-risk patients, and CMV disease occurred exclusively in this group with delayed or absent virus-specific T-cell recovery. In contrast, 16/24 intermediate-risk patients showed CMV-specific T cells. Our data suggest that CMV infection and disease rates are elevated in high-risk patients with delayed CMV-specific T-cell immune reconstitution and lower in those with early recovery of T-cell immunity. We recommend preferring CMV seropositive donors for CMV seropositive recipients, as this should lead to durable CMV-specific T-cell responses soon after transplantation with consecutive protection from CMV disease.

Today, 30 years after the onset of the HIV pandemic, although treatment strategies have considerably improved, there is still no cure for the disease. Recently, we described a successful hematopoietic stem cell transplantation in an HIV-1–infected patient, transferring donor-derived cells with a natural resistance against HIV infection. These hematopoietic stem cells engrafted, proliferated, and differentiated into mature myeloid and lymphoid cells. To date, the patient has not required any antiretroviral treatment, more than 4 years after allogeneic transplantation. In the analysis of peripheral blood cells and different tissue samples, including gut, liver, and brain, no viral load or proviral DNA could be detected. Our report raises the hope for further targeted treatment strategies against HIV and represents a successful personalized treatment with allogeneic stem cells carrying a beneficial gene. However, this case has ignited a controversy regarding the question of whether this patient has achieved complete eradication of HIV or not. Here we give an update on open questions, unsolved aspects, and clinical consequences concerning this unique case.

We analyzed cytomegalovirus (CMV) infection risk factors and immune reconstitution kinetics in 89 patients after allogeneic stem cell transplantation (allo-SCT). The use of alemtuzumab for in vivo T cell depletion (TCD) had, besides the donor/recipient CMV serostatus, the strongest influence on the CMV infection risk in univariate and multivariate analyses. In comparison to without use of in vivo TCD, the CMV infection risk [hazard ratio (HR)] was 4.82-fold after TCD with alemtuzumab, but only 1.40-fold after TCD with antithymocyte globulin (ATG). Alemtuzumab strongly depressed CD4(+) and CD8(+) T cell reconstitution, whereas ATG only delayed CD4(+) T cell reconstitution. Considering the reconstitution kinetics of CD4(+) and CD8(+) T cells, CMV-specific CD8(+) T cells, NK cells and the IgG concentration, only a low day +60 NK cell count (< or =161 versus >161/microl) was significantly associated with CMV infection development (HR 2.92, p = 0.034). CMV-specific CD8(+) T cells were detected in 57% of patients with a CMV-seropositive donor, but in none of the patients with a CMV-seronegative donor on day +30 (p = 0.01). Our data indicate that the type of in vivo TCD (alemtuzumab or ATG) differentially influences both the CMV infection risk and CD4(+)/CD8(+) T cell reconstitution kinetics in patients after allo-SCT.

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Although thymoglobulin and alemtuzumab are frequently used in hematopoietic stem cell transplantation (HSCT), little is known of their effects on NK cells, which mediate important functions in post-transplantation immunology. In the present study, we determined NK cell death in vitro using propidium iodide and Annexin V. The NK cell activity in 34 patients at day þ 30 after allogeneic HSCT was assessed using the CD107a assay. Alemtuzumab and thymoglobulin were similarly very potent in inducing NK cell death in vitro. Even in low concentrations (o1 lg/ml) the antibodies induced apoptosis and necrosis in a relevant percentage of NK cells (430%). However, the number of tumor reactive (CD107a þ ) NK cells was 13.16 per ll and 1.15 per ll (mean) in patients receiving T-cell depletion with 6 mg/kg thymoglobulin and in patients receiving 100 mg alemtuzumab, respectively (P ¼ 0.02). Although thymoglobulin and alemtuzumab are equally NK cell toxic in vitro, the recovery of NK cell frequency and anti-tumor reactivity is reduced in recipients of alemtuzumab. Our findings can be explained by a longer half-life of alemtuzumab as compared to active thymoglobulin under therapeutic conditions. Prolonged immunosuppression with increased risk of infections and tumor relapse are a potential threat to patients undergoing HCST and receiving alemtuzumab as T-cell depletion.

Short-term treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF) followed by leukapheresis (LPH) is the common procedure for obtaining CD34+ peripheral blood progenitor cells from allogeneic donors. Bone pain, headache and flu-like symptoms are well-known G-CSFassociated side effects that occur for a short duration. In addition, fatigue and gastrointestinal or cardiovascular symptoms may also be observed, but these are rare complications.D 'Souza et al. (2008) reported on the different adverse events experienced by healthy donors after stimulation with rhG-CSF, of which pulmonary toxicity was a prominent finding. Here, we report two cases of healthy donors with lung injury and interstitial pneumonia, respectively, and haemoptysis.A 31-year-old woman, who was an unrelated donor, received G-CSF (lenograstim, 8·5 μg kg −1 day −1 ) over 5 days, without unexpected adverse events, for peripheral blood stem cell mobilisation. The white blood cell (WBC) count at the time of LPH (day 0) was 39·9 × 10 9 L −1 . Three days after LPH (day 3), she experienced symptoms of common cold. Unilateral otitis media was diagnosed, and she was treated with oral amoxicillin for 2 days. Forty-eight hours later (day 5), she was admitted to the hospital because of fever (38·3 • C), thoracic pain and dyspnoea. Massively increased levels of C-reactive protein (CRP; maximum 290 mg L −1 ) and procalcitonin (17 μg L −1 ) were detected. At this time, the WBC count was 41·0 × 10 9 L −1 . Computed tomography (CT) of the chest indicated patchy consolidations in the middle and lower lung fields of both lungs. In addition, papular skin lesions, muscle pain and impairment of renal function (creatinine 1·7 mg dL −1 ) was noted. Due to worsened respiratory distress (SO 2 92% on 8 L O 2 min −1 ) and bilateral pleural effusions, the donor was temporarily monitored in the intensive care unit (days 7 and 8).As the symptoms likely appeared to be associated with a disseminated overwhelming inflammatory reaction after G-CSF administration, high-dose steroid treatment (prednisone, 3·5 mg kg −1 ) was initiated. Bronchoscopy on day 7 demonstrated normal respiratory mucosa. Transbronchial biopsy of lung tissue and open biopsy of skin lesions showed infiltration by neutrophils. Microbiologic analyses failed to detect any microbes. All tests for autoantibodies and virus-specific polymerase chain reactions (PCRs) remained negative (rheumatoid factor; antinuclear antibodies; extractable nuclear antigen Correspondence: Katrin Wetzko, Universitätsklinikum Carl Gustrav Carus,