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Autoaggression syndrome resembling acute graft-versus-host disease grade IV after autologous peripheral blood stem cell transplantation for breast cancer.

Acute graft-versus-host disease (aGVHD) after autologous progenitor cell transplantation has been associated with blood transfusion or cyclosporine. Mild aGVHD grades I–II, identified as autoaggression or engraftment syndrome, has recently been described in autologous progenitor transplantation. Here, we report the first case of pathologically documented grade IV aGVHD after autologous peripheral blood progenitor cell transplantation in a patient with breast cancer. The allogeneic origin was excluded by molecular techniques, and no cyclosporine or cytokines were administered.

Administration of post-autologous PBSCT rhG-CSF is associated with long-term low concentrations of bone marrow hematopoietic progenitor cells.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been widely used after autologous peripheral blood stem cell transplant (APBSCT) in an attempt to reduce the duration of neutropenia, but whether this treatment has any influence on long-term engraftment remains unknown. We have retrospectively analyzed data from breast cancer patients to compare post-APBSCT rhG-CSF administration in terms of the short-term benefit and myeloid marrow regeneration after 1 year. Group A included 10 patients not treated with post-APBSCT rhG-CSF, while groups B and C comprised 15 and 13 patients treated with this drug from days +1 and +6, respectively. No differences among the three groups were found in age, diagnosis, previous chemo-radiotherapy, CD34+/CD71− cell concentration in pre-transplant bone marrow (BM), mobilization schedule, CD34+ cell yield, conditioning regimen and post-transplant radiotherapy. Post-APBSCT rhG-CSF was shown to accelerate neutrophil recovery, but there were no significant differences in platelet recovery, transfusion requirements, days of fever, antibiotic administration or inhospital stay. With regard to BM hematopoietic precursors 1 year after APBSCT, significantly lower concentrations of total CD34+cells, committed CD34+/CD33+ subsets, and more immature CD34+/CD71− cells were found in both groups B and C compared with patients not having received the cytokine (group A). Thus, post-APBSCT rhG-CSF administration does not appear to beneficially affect procedure outcome, and might even impair long-term marrow hematopoiesis. Bone Marrow Transplantation (2001) 27, 1287–1292.

Bone marrow steady-state CD34+/CD71- cell content is a predictive value of rG-CSF-mobilized CD34+ cells

Thirty-four patients diagnosed with breast cancer were included in a prospective study evaluating the bone marrow (BM) CD34+/CD71− cell content, as a predictive parameter of the CD34+ cell mobilization after rG-CSF administration. Analysis of the concentration of medullary CD34+/CD71− cells before priming schedules was significantly related with the collection of CD34+ cells in apheresis day 1 (P = 0.03, r = 0.36), apheresis day 1 + day 2 (P = 0.01, r = 0.42) or the total CD34+ cells collected (P = 0.005, r = 0.47). A BM CD34+/CD71− cell concentration greater than or less than a cut-off value of 30/μl was significantly associated with the yield of CD34+ cells collected by cytapheresis procedures (mean values 3.12 × 106/kg, and 2.19 × 106/kg, respectively, P = 0.013). These results suggest that in breast cancer patients undergoing priming with rG-CSF, steady-state BM CD34+/CD71− measurement is a relevant predictive parameter of CD34+ mobilization.

Persistent cytotoxic T lymphocyte expansions after allogeneic haematopoietic stem cell transplantation: kinetics, clinical impact and absence of STAT3 mutations.

Peripheral expansion of cytotoxic T lymphocytes (CTL) derived from the graft in the initial stages of allogeneic haematopoietic stem cell transplantation (alloHSCT) immune recovery is a well‐known physiological event. The description of symptomatic large granular lymphocyte leukaemia in this setting may generate uncertainty, mostly in those cases in which the CTL expansion (CTLe) persists beyond the early transplantation period. We aimed to assess the nature of CTLe during the post‐alloHSCT period in 154 adult patients with a long‐term surveillance. We studied the longitudinal kinetics of those expansions, their relationship to clinical events, and their phenotypic and molecular features, including recently reported CTL leukaemia‐STAT3 mutations. Persistent relative CTLe cases are frequent (49%), related with thymoglobulin prophylaxis (P ≤ 0·001), acute graft‐versus‐host disease (GVHD, P = 0·02), and reduced intensity conditioning (P = 0·04). Absolute CTLe are scarce (9%) and related to chronic GVHD. T cell receptor rearrangement was reported as clonal and oligoclonal in the majority of patients with CTLe. The absence of STAT3 mutations and the CD8/CD4 declining longitudinal kinetics in the late period supports its benign nature, expressed clinically by the null detrimental impact of these expansions on post‐transplant outcome and/or serious infectious events.

Faggot cells in an HIV-positive patient with inv(16)/therapy-related acute myeloid leukaemia.

A 32-year-old human immunodeficiency virus (HIV)-positive male presented with fever and some haemorrhagic vesicles on the soft palate. Three years previously, he had been diagnosed with stage IVB, nodular sclerosis Hodgkin lymphoma, treated with six cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD), and achieved complete remission. On admission, a full blood count showed: white cell count 67AE4 · 10/l, haemoglobin concentration 85 g/l and platelet count 10 · 10/l. Peripheral blood films showed 10% blasts (some with granules), 25% promonocytes and 6% eosinophils. A variable number of Auer rods were observed in some neutrophils and band forms, occasionally being numerous (top). A bone marrow aspirate showed blast cells, promonocytes, monocytes, eosinophils and eosinophil precursors. In addition there were faggot cells – maturing cells of neutrophil lineage containing bundles of Auer rods (bottom). Cytochemical studies showed a proportion of cells positive for myeloperoxidase, chloroacetate esterase and butyrate esterase. Periodic acid–Schiff (PAS) positivity was observed in some atypical eosinophils. Immunophenotypic analysis showed two abnormal populations: the first of these accounted for 15% of the events and showed a CD34+, CD117+, CD33+, CD13++, CD15±, HLA)DR+, CD45+, cMPO+ and lysozyme–phenotype; the second accounted for 60% and showed a CD34), CD117±, CD13+, CD15+, HLA-DR+, CD11b+, CD14+, CD64+, CD36+, CD45++, cMPO± and lysozyme+ phenotype. Interphase fluorescence in situ hybridization analysis revealed inv(16) and excluded t(15;17). Cytogenetic analysis showed 47,XY,+8,inv(16)(p13q22)[20]. Molecular analysis confirmed inv(16) (MYH11-CBFB/ABL1 ratio:12AE47). The final diagnosis was therapy related-acute myeloid leukaemia (AML) with +8 and inv(16). He received two cycles of induction chemotherapy without attaining complete remission. Faggot cells are very characteristic of acute promyelocytic leukaemia but, as illustrated by this patient, they cannot be regarded as specific. They are a very uncommon feature of AML associated with inv(16).

Bone-marrow immunophenotypic analysis allows the identification of high risk of progression and immune condition-related monoclonal gammopathy of undetermined significance

Background. Monoclonal gammopathy of undetermined significance (MGUS) progresses to plasma cell dyscrasia at a rate of 1% per year. A high prevalence of MGUS has been noted in series of patients with immune disorders or chronic infections. Methods. Retrospective cohort and a cross-sectional study to analyze the prognostic value of aberrant (CD38+ +CD138+ CD19-CD45weak) to normal phenotype (CD38+ +CD138+ CD19+CD45+) bone-marrow plasma cells ratio (A/N ratio) for the development of a plasma cell dyscrasia and the association with the presence of a chronic immune disorder. Results. A total of 322 patients were included with a median follow-up of 46 months. Analysis for progression revealed an increased A/N ratio as the main independent prognostic variable. A significant association between a reduced A/N ratio and the diagnosis of a chronic immune condition was found. Using receiver-operating characteristic analysis we created an A/N ratio range from 4 to 0.20. Values of 4 or higher define a group at high risk of progression (OR 10.7). A/N values of 0.20 or lower are associated with immune disorders or chronic infections (OR 20.9). Conclusions. Extreme values of the A/N ratio seem to be related with two different conditions: high risk of progression, and immune condition-related MGUS.

Transient bone marrow lymphoproliferation after umbilical cord blood transplantation: Exacerbated reconstitution of B-cell ontogeny in adults†

We describe a transient bone marrow heterogeneous B-cell lymphoproliferation with a complex spectrum of cytological, phenotypic, molecular, and immune features in the setting of adult patients with acute myeloid leukemia following umbilical cord blood transplantation procedure. In our view, the lymphoproliferation described herein could add another element to the differential diagnosis of post-transplant lymphoproliferative disorders.

Transient massive peripheral blood blastosis in patient with renal clear-cell carcinoma after treatment with high-dose recombinant interleuklin-2

A 35-year-old woman presented at the Orthopaedic Department with pain in the right hip. Pelvic CT showed a lytic lesion in the sacrum with an associated soft-tissue mass. CT-guided needle biopsy of the bone lesion disclosed clear-cell carcinoma metastasis. Further more, abdominal CT revealed a well-defi ned mass in the left kidney measuring 8×9 cm; thoracic CT showed other abnormalities. A nephrectomy was done for diagnostic and therapeutic purposes. As a result of the diagnosis of stage IV clear-cell renal carcinoma, which had a Fuhrman grade IV, an Eastern Cooperative Oncology Group grade 1, bone dissemination, and a high-risk level according to the University of California Los Angeles integrated staging system, high-dose recombinant interleukin-2 (HD-IL2) was started after recovery from surgery. The patient received 600 000 U/kg of intravenous IL-2 every 8 h for 5 days in two courses, the fi rst course beginning on day 1 and the second beginning on day 15. Throughout HD-IL2 administration, the patient also received commonly used concomitant medication. Baseline blood count before the second course of HD-IL2 was 11·1×10/L of leucocytes (44% neutrophils, 42% lymphocytes, 7% monocytes, 6% eosinophils, and 1% basophils), 114 g/L of haemoglobin, and 391×10/L of platelets. After the fourth dose of the second course of HD-IL2, the patient presented tachycardia (130 bpm), hypotension (70/30 mmHg), and oligoanuria with impairment of renal function (creatinine level 176·8 μmol/L). Metabolic acidosis (pH 7·2; HCO3 14·8 mEq/L) was also recorded. Finally, hypoxaemia (sO2 92%) and radiological bilateral interstitial infi ltrates, shown by chest radiography, revealed pulmonary oedema. The patient was subsequently admitted to the intensivecare unit where supplemental oxygen (3 L/min) and HCO3 were then initiated. Additionally, hypotension was treated with both crystalloids and norepinephrine administration (0·2 μg/kg per min). HD-IL2 was discontinued after the 12th dose of the second course because of its toxic eff ects. Symptoms resolved 2 days after the last dose of HD-IL2 was given; however, blood count showed leucocytosis (22×10/L) with mild anaemia (Haemoglobin 104 g/L) and thrombocytopenia (113×10/L). Diff erential blood count showed 53% undiff erentiated blast cells; 53% erythroblasts were also counted (fi gure). Acute leukaemia was ruled out by means of a bone marrow aspirate done 16 h later. Bone marrow smears showed a hypercellular marrow with a normal myeloid and erythroid ratio, a leftward shift of myeloid series with 2% undiff erentiated blast cells and 11% myeloid blast cells, and predominance (48%) of semimature and, to a lesser extent, mature granulopoietic cells with no dysplastic features. Megakaryocytic hyperplasia was also noted. No metastases were seen. Cytogenetic analysis done on 30 metaphases from unstimulated culture of the bone-marrow sample showed a 46XX karyotype with no structural chromosome anomaly. Blood count returned to baseline levels within the following 2 days. 6 weeks after the last dose of HD-IL2 had been given, an enlargement (35% increase in the larger diameter) of the bone mass was noted. Because the disease was refractory to immunotherapy, the patient has started treatment with sunitinib (SU11248) within a clinical trial. Clear-cell renal carcinoma is the most common adult renal neoplasm. HD-IL2 received approval from the Food and Drug Administration in 1992 for the treatment of patients with stage IV renal-cell carcinoma, on the basis of results of 255 patients who were included in seven phase II trials. In selected patients, the complete response rate was 7% (median follow up of 54 months, range 3–131 months) with actuarial curves predicting that 60% would be free Lancet Oncol 2007; 8: 275–76