Intermediate-dose cytarabine plus mitoxantrone versus standard-dose cytarabine plus daunorubicin for acute myeloid leukemia in elderly patients.

Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous infusion cytarabine plus daunorubicin (DA). Patients and methods: Patients with newly diagnosed AML >60 years were randomized to receive either intermediate-dose cytarabine (1000 mg/m2 twice daily on days 1, 3, 5, 7) plus mitoxantrone (10 mg/m2 days 1-3) (IMA) or standard induction therapy with cytarabine (100 mg/m2 continuously days 1-7) plus daunorubicin (45 mg/m2 days 3-5) (DA). Patients in complete remission after DA received intermediate-dose cytarabine plus amsacrine as consolidation treatment, whereas patients after IMA were consolidated with standard-dose cytarabine plus mitoxantrone. Results: Between February 2005 and October 2009, 485 patients were randomized; 241 for treatment arm DA and 244 for IMA; 76% of patients were >65 years. The complete response rate after DA was 39% [95% confidence interval (95% CI): 33-45] versus 55% (95% CI: 49-61) after IMA (odds ratio 1.89, P = 0.001). The 6-week early-death rate was 14% in both arms. Relapse-free survival curves were superimposable in the first year, but separated afterwards, resulting in 3-year relapse-free survival rates of 29% versus 14% in the DA versus IMA arms, respectively (P = 0.042). The median overall survival was 10 months in both arms (P = 0.513). Conclusion: The dose escalation of cytarabine in induction therapy lead to improved remission rates in the elderly AML patients. This did not translate into a survival advantage, most likely due to differences in consolidation treatment. Thus, effective consolidation strategies need to be further explored. In combination with an effective consolidation strategy, the use of intermediate-dose cytarabine in induction may improve curative treatment for elderly AML patients.

Plerixafor with and without chemotherapy in poor mobilizers: results from the German compassionate use program.

The CXCR4-inhibitor plerixafor mobilizes hematopoietic stem cells amplifying the effects of granulocyte-CSF (G-CSF). Before approval plerixafor was used in a compassionate use program (CUP) for patients who failed a previous mobilization. In the German CUP 60 patients from 23 centers (median age 56.5 years (2-75)) were given 240 µg/kg plerixafor SC 9-11 h before apheresis. A total of 78.3% (47/60) received G-CSF for 4 days before plerixafor administration; 76.6% of those (36/47) yielded at least 2.0 × 10(6) CD34(+) cells/µL. The median cell yield was 3.35 × 10(6) CD34+ cells/kg (0-29.53). Nine patients received plerixafor alone or with G-CSF for less than 4 days mobilizing a median of 3.30 × 10(6) CD34+ cells/kg (1.6-5.6). There was no significant difference between G-CSF application for 4 days and for a shorter period of time (P=0.157). A total of 47 patients received plerixafor plus G-CSF combined with chemotherapy yielding a median of 3.28 × 10(6) CD34+ cells/kg (0-24.79). In all, 40 of 60 patients (66.7%) proceeded to transplantation, and achieved a timely and stable engraftment. Side effects were rare and manageable. In conclusion, mobilization with plerixafor in poor mobilizers is safe and results in a sufficient stem cell harvest in the majority of patients.

[Severe leukopenia and bone marrow hypoplasia with gelatinous transformation in anorexia nervosa]. / Schwere Leukopenie und Knochenmarkhypoplasie mit gelatinöser Transformation bei Anorexia nervosa.

HISTORY AND ADMISSION FINDINGS: A 26-year-old woman was admitted because of excessive weight loss: her body mass index was 11.3 kg/m (2). She reported an adequate food intake and denied fear of gaining weight. INVESTIGATIONS: The leukocyte count on admission was 2.0/nl. Bone marrow biopsy showed gelatinous bone marrow transformation with hypocellularity. Psychiatric examination and observation of the patient's eating behavior revealed symptoms typical of anorexia nervosa. DIAGNOSIS, TREATMENT AND COURSE: Because of the diagnosis of anorexia nervosa behaviour therapy was started. During the following months the patient continually gained weight. But it took nine months for leukocyte count to be normal, by which time her body mass index had risen to 17.8 kg/m (2). CONCLUSION: Severe weight loss in anorexia nervosa may lead to leukopenia and gelatinous bone marrow transformation. The abnormal leukocyte count can become normal by maintaining body weight within the normal range.

Elevated serum thrombopoietin and interleukin-6 concentrations in thrombocytosis associated with inflammatory bowel disease.

Reactive thrombocytosis is a typical feature in inflammatory bowel disease (IBD). The question arose as to whether the normal negative feedback regulation of the concentration of thrombopoietin (TPO) in blood was altered in IBD patients. We measured serum immunoreactive TPO in 30 patients with active IBD, 29 patients with inactive IBD, and 56 healthy controls. The results were related to platelet and leukocyte counts and to the serum concentration of interleukin 6 (IL-6). Patients with active IBD exhibited significantly increased TPO levels (medians 112 pg/ml vs. 90 pg/ml in controls, p < 0.05) in association with thrombocytosis (428 platelets/nl blood vs. 241 platelets/nl blood in controls), leukocytosis, and increased IL-6 levels (12.9 pg/ml vs. 2.5 pg/nl in controls). In patients with inactive IBD, only platelets (322/nl) and leukocytes were above normal. Although the observation of increased TPO and IL-6 levels provides an explanation for the occurrence of thrombocytosis in IBD, the pathogenetic mechanisms underlying the elevated TPO level still need to be identified.

Systemic infection of an immunocompromised patient with Methylobacterium zatmanii.

We describe the identification of Methylobacterium zatmanii as the causative agent of bacteremia and fever in an immunocompromised patient. The patient, a 60-year-old man, had a 5-month history of acute myeloid leukemia and had been on chemotherapy throughout this period. Seven days after the onset of neutropenia, the patient developed fever. The combination of ciprofloxacin, co-trimoxazole, imipenem, amikacin, and vancomycin led to a complete defervescence. On subculture from six positive blood cultures, the organism grew only on buffered charcoal yeast extract agar and not on standard agars. Identification by universal PCR and subsequent sequence analysis of the amplified 16S rRNA gene segment was achieved. This identification by molecular biology techniques was confirmed by conventional biochemical tests. To our knowledge, this is the first description of M. zatmanii isolated from patient material.

Serum thrombopoietin and interleukin 6 concentrations in tumour patients and response to chemotherapy-induced thrombocytopenia.

The relation between the number of platelets in blood and the concentrations of immunoreactive thrombopoietin (TPO), interleukin 6 and interleukin 11 (IL-6, IL-11) was studied in the sera of 32 normal subjects, of 29 untreated tumour patients and of 6 tumour patients following chemotherapy with ifosfamide, carboplatin and etoposide (ICE). Platelet counts, TPO and IL-6 concentrations were higher than normal in blood of tumour patients before chemotherapy. However, no statistical relation existed between these variables. Following chemotherapy, the number of circulating platelets decreased reaching a nadir at d 10-13, while the serum concentration of TPO increased concomitantly. Circulating IL-6 did not increase during chemotherapy-induced thrombocytopenia. IL-11 was not detectable in any serum. Thus, the reactive thrombocytosis in tumour patients could be related to elevated TPO and IL-6 levels. In contrast to circulating TPO, however, neither serum IL-6 nor IL-11 levels increase significantly in thrombocytopenia following myelosuppressive. chemotherapy.

Serum vascular endothelial growth factor (VEGF), a prognostic indicator in sarcoma and carcinoma patients.

Tumor growth and the development of metastases are dependent on the local formation of new blood vessels. A major role in the induction of angiogenesis has been assigned to vascular endothelial growth factor (VEGF), a tumor cell-derived endothelium-specific mitogen. We studied whether blood levels of VEGF are increased in sarcoma and carcinoma patients. In addition, we tested whether data from measurements of serum VEGF are of prognostic value with respect to tumor remission during chemotherapy courses of sarcoma patients. First, we measured the concentration of VEGF in the sera of 60 normal volunteers and of 25 untreated patients suffering from solid tumors (13 sarcomas, 12 carcinomas). Second, we studied the level of serum VEGF in 9 tumor patients during 4 courses of ICE-chemotherapy (ifosfamide, carboplatin, etoposide). VEGF was measured by enzyme-linked immunoassay. The concentrations of serum VEGF were significantly higher (P <0.0001) in untreated sarcoma (933+/-132 pg/ml) and carcinoma (1,257+/-169 pg/ml) patients compared to those of normal subjects (239+/-21 pg/ml). The concentration of VEGF was roughly proportional to the tumor mass. A significant fall in serum VEGF occurred in the 6 patients who responded to chemotherapy with tumor remission but not in the patient who were resistant. The concentration of serum VEGF is an indicator of tumor growth in sarcoma and carcinoma patients and thus of prognostic value. Serum VEGF measurements may be clinically useful for monitoring tumor regression in sarcoma patients undergoing chemotherapy.