M Leithäuser

University of Rostock, Rostock, Mecklenburg-Vorpommern, Germany

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Publications (26)119.35 Total impact

  • Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 04/2013; · 10.16 Impact Factor
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    ABSTRACT: OBJECTIVES: The aims of the presented study were to validate tools evaluating physical functioning (PF) after allogeneic hematopoietic stem cell transplantation (alloHSCT) and to analyze the impact of the clinical course on PF. METHODS: Forty patients undergoing alloHSCT were enrolled in a prospective trial which included evaluation of muscle strength (grip test, CITEC dynamometer), endurance (2-min walk test), anxiety and depression (Hospital Anxiety and Depression Scale), fatigue (Modified Fatigue Impact Scale and Brief Fatigue Inventory), and physical activity (Human Activity Profile-HAP) before (t1) and 1 (t2) and 3 (t3) months after alloHSCT. RESULTS: At t2, all patients showed a 6 % (p = 0.02) loss of muscle strength which was higher in patients with acute graft-versus-host disease (aGVHD) (12 %). While patients without aGVHD recovered at t3, the loss of muscle strength was progressive in patients with aGVHD. The grip test results correlated with the results of detailed measurement of muscle strength by CITEC dynamometer (r = 0.4-0.8, p = 0.05-0.001). Moreover, the HAP scores correlated with physical performance. CONCLUSION: The results demonstrate that loss of PF occurs during the first month followed by a regain during the subsequent 2 months in the absence of aGVHD. The HAP and the grip test may serve as surrogate marker for the strength loss in the course of aGVHD.
    Supportive Care in Cancer 11/2012; · 2.09 Impact Factor
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    ABSTRACT: We evaluated the frequency and prognostic impact of meningeal dissemination (MD) in immunocompetent adult patients with primary central nervous system lymphoma treated in a randomized phase III trial. MD was evaluated at study entry and defined by lymphoma proof in the meningeal compartment detected by at least one of the following methods: cerebrospinal fluid (CSF) cytomorphology, detection of clonal B cells by IgH PCR in CSF or contrast enhancement of the leptomeninges on magnetic resonance imaging (MRI). Data on MD were available in 415 patients, of those, MD was detected in 65 (15.7%): in 44/361 (12.2%) by CSF cytomorphology, in 16/152 (10.5%) by PCR and in 17/415 (4.1%) by MRI. Major patients' characteristics and therapy did not significantly differ between patients with MD (MD+) versus those without MD (MD-). There was a significant correlation of MD with CSF pleocytosis (>5/μl; P < 0.0001), but no correlation with CSF protein elevation (>45 mg/dl). Median progression-free survival was 6.7 months [95% confidence interval (CI) 0-14.5] in MD+ and 8.3 months (5.7-10.8) in MD- patients (P = 0.95); median overall survival was 21.5 months (95% CI 16.8-26.1) and 24.9 months (17.5-32.3), respectively (P = 0.98). MD was detected infrequently and had no impact on outcome in this trial.
    Annals of Oncology 03/2012; 23(9):2374-80. · 7.38 Impact Factor
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    ABSTRACT: Post-transplantation lymphoproliferative disorder (PTLD) develops in 1-10% of transplant recipients and can be Epstein-Barr virus (EBV) associated. To improve long-term efficacy after rituximab monotherapy and to avoid the toxic effects of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy seen in first-line treatment, we initiated a phase 2 trial to test whether the subsequent use of rituximab and CHOP would improve the outcome of patients with PTLD. In this international multicentre open-label phase 2 trial, treatment-naive adult solid-organ transplant recipients diagnosed with CD20-positive PTLD who had failed to respond to upfront immunosuppression reduction received four courses of rituximab (375 mg/m(2) intravenously) once a week followed by 4 weeks without treatment and four cycles of CHOP every 3 weeks. In case of disease progression during rituximab monotherapy, CHOP was started immediately. Supportive therapy with granulocyte-colony stimulating factor after chemotherapy was mandatory and antibiotic prophylaxis was recommended. The primary endpoint was treatment efficacy measured as response rates in all patients who completed treatment with rituximab and CHOP, per protocol, and response duration, in all patients who completed all planned therapy and responded. Secondary endpoints were frequency of infections, treatment-related mortality, and overall survival. This study is registered at ClinicalTrials.gov, number NCT01458548. 74 patients were enrolled between Dec 12, 2002 and May 5, 2008, of whom 70 patients were eligible to receive treatment. PTLD was of late type in 53 (76%) of 70 patients, monomorphic in 67 (96%) of 70, and histologically EBV associated in 29 (44%) of 66 cases. Four of 70 patients did not receive CHOP. 53 of 59 patients had a complete or partial response (90%, 95% CI 79-96), of which 40 (68%, 55-78) were complete responses. At data cutoff (June 1, 2011) median response duration in the 53 patients who had responded to treatment had not yet been reached (>79·1 months). The main adverse events were grade 3-4 leucopenia in 42 of 62 patients (68%, 55-78) and infections of grade 3-4 in 26 of 64 patients (41%, 29-53). Seven of 66 patients (11%, 5-21) had CHOP-associated treatment-related mortality. Median overall survival was 6·6 years (95% CI 2·8-10·4; n=70). Our results support the use of sequential immunochemotherapy with rituximab and CHOP in PTLD. F Hoffmann-La Roche, Amgen Germany, Chugaï France.
    The Lancet Oncology 12/2011; 13(2):196-206. · 25.12 Impact Factor
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    ABSTRACT: HISTORY AND ADMISSION FINDINGs: A 61-year-old woman was found unconscious by her husband. The emergency doctor detected hypoglycemia (blood glucose 1.7 mmol/l). This was the first such event, the patient had not been known to have diabetes mellitus. At admission the physical examination and the laboratory findings revealed no abnormalities. A fasting test was aborted shortly after the start because of the onset of neurological symptoms. An insulinoma was excluded by detecting suppressed levels of insulin and C-peptide. Computed tomography of the abdomen revealed a mesenteric tumour of 9 cm in diameter, which was identified immunhistologically as a grade 1 follicular lymphoma (FL).  After exclusion of endocrinological causes the recurrent hypoglycaemia was diagnozed as part of a paraneoplastic syndrome associated with a non-islet cell tumour hypoglycaemia (NICTH) with a newly diagnosed FL. Specific medication with the CD20 antibody rituximab (375 mg/m2, once per week for a total of four cycles) was initiated. There were no further episodes of hypoglycaemia. After one year the patient remains free of any symptoms. After exclusion of any endocrinological reasons for hypoglycemia, differential diagnosis should include NICTH as paraneoplastic syndrome. In rare cases a hematological malignancy may be the underlying disease. The specific treatment of this disease likewise represents the causal treatment of NICTH.
    DMW - Deutsche Medizinische Wochenschrift 12/2011; 136(49):2542-6. · 0.65 Impact Factor
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    ABSTRACT: High-dose methotrexate is the standard of care for patients with newly diagnosed primary CNS lymphoma. The role of whole brain radiotherapy is controversial because delayed neurotoxicity limits its acceptance as a standard of care. We aimed to investigate whether first-line chemotherapy based on high-dose methotrexate was non-inferior to the same chemotherapy regimen followed by whole brain radiotherapy for overall survival. Immunocompetent patients with newly diagnosed primary CNS lymphoma were enrolled from 75 centres and treated between May, 2000, and May, 2009. Patients were allocated by computer-generated block randomisation to receive first-line chemotherapy based on high-dose methotrexate with or without subsequent whole brain radiotherapy, with stratification by age (<60 vs ≥60 years) and institution (Berlin vs Tübingen vs all other sites). The biostatistics centre assigned patients to treatment groups and informed local centres by fax; physicians and patients were not masked to treatment group after assignment. Patients enrolled between May, 2000, and August, 2006, received high-dose methotrexate (4 g/m(2)) on day 1 of six 14-day cycles; thereafter, patients received high-dose methotrexate plus ifosfamide (1·5 g/m(2)) on days 3-5 of six 14-day cycles. In those assigned to receive first-line chemotherapy followed by radiotherapy, whole brain radiotherapy was given to a total dose of 45 Gy, in 30 fractions of 1·5 Gy given daily on weekdays. Patients allocated to first-line chemotherapy without whole brain radiotherapy who had not achieved complete response were given high-dose cytarabine. The primary endpoint was overall survival, and analysis was per protocol. Our hypothesis was that the omission of whole brain radiotherapy does not compromise overall survival, with a non-inferiority margin of 0·9. This trial is registered with ClinicalTrials.gov, number NCT00153530. 551 patients (median age 63 years, IQR 55-69) were enrolled and randomised, of whom 318 were treated per protocol. In the per-protocol population, median overall survival was 32·4 months (95% CI 25·8-39·0) in patients receiving whole brain radiotherapy (n=154), and 37·1 months (27·5-46·7) in those not receiving whole brain radiotherapy (n=164), hazard ratio 1·06 (95% CI 0·80-1·40; p=0·71). Thus our primary hypothesis was not proven. Median progression-free survival was 18·3 months (95% CI 11·6-25·0) in patients receiving whole brain radiotherapy, and 11·9 months (7·3-16·5; p=0·14) in those not receiving whole brain radiotherapy. Treatment-related neurotoxicity in patients with sustained complete response was more common in patients receiving whole brain radiotherapy (22/45, 49% by clinical assessment; 35/49, 71% by neuroradiology) than in those who did not (9/34, 26%; 16/35, 46%). No significant difference in overall survival was recorded when whole brain radiotherapy was omitted from first-line chemotherapy in patients with newly diagnosed primary CNS lymphoma, but our primary hypothesis was not proven. The progression-free survival benefit afforded by whole brain radiotherapy has to be weighed against the increased risk of neurotoxicity in long-term survivors.
    The Lancet Oncology 10/2010; 11(11):1036-47. · 25.12 Impact Factor
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    ABSTRACT: Myelopathy due to epidural spinal cord compression is rare in patients with malignant lymphoma and most of these patients are diagnosed with high-grade lymphoma. An epidural growth of low-grade lymphoma is even more unusual. Due to this low incidence, therapeutic experience for this entity is limited. We report the outcome of 3 consecutive patients with primary spinal epidural follicular lymphoma (FL). Due to the clinical disorders of the patients and despite the localized disease, we used an intensive multimodal therapy concept consisting of spinal decompression, systemic (immuno)chemotherapy and local irradiation. All patients improved in their medical condition; 2 achieved a complete remission, 1 of these with long-term remission. In contrast to the established irradiation therapy for early-stage FL, an intensive multimodal therapy concept should be initiated in patients with primary spinal epidural FL. With this approach, a fast improvement of the symptoms and long-term disease-free survival is possible.
    Onkologie 01/2010; 33(7):381-4. · 1.00 Impact Factor
  • C Kahl, M Leithäuser, C Junghanss, F Prall, M Freund
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    ABSTRACT: A 47-year-old woman was admitted to our emergency room because of anemia and acute tonsillitis. She reported recurrent fever and a sore throat. Clinical examination and CT scans showed general lymph node swelling and liver enlargement. In the course of the disease she developed pancytopenia with neutropenic fever, pleuropneumonia, and deep vein thrombosis. The histological examination of a lymph node showed a reactive, EBV-associated lymphadenitis. The examination of the bone marrow showed an activated marrow. The diagnosis of an active EBV infection was established with 2 x 10(6)/ml EBV gene copies in the blood. In addition, systemic lupus erythematosus was diagnosed because of the typical autoantibody constellation and clinical findings. The immunohematological examination showed autoantibodies against the three blood cell compartments. Because of the severe pancytopenia as a result of the EBV- and SLE-associated autoantibodies and despite recurrent infections, we initiated immunosuppressive therapy with low-dose corticosteroids. This therapy resulted in normalization of the blood counts. Anitibody levels and the EBV genome levels became negative.
    Der Internist 03/2009; 50(6):734-9. · 0.33 Impact Factor
  • C. Kahl, M. Leithäuser, C. Junghanss, F. Prall, M. Freund
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    ABSTRACT: Eine 47-jährige Patientin stellte sich mit ausgeprägter Anämie und Tonsillitis in der Notaufnahme unserer Klinik vor. Sie berichtete über rezidivierendes Fieber und Halsschmerzen. In der Diagnostik fielen eine generalisierte Lymphknotenschwellung und eine Hepatomegalie auf. Im weiteren Verlauf entwickelte die Patientin eine Panzytopenie mit rezidivierendem neutropenem Fieber, eine Pleuropneumonie und eine tiefe Beinvenenthrombose. Die histologische Untersuchung eines Lymphknotens ergab eine reaktive Epstein-Barr-Virus- (EBV-) getriggerte Lymphadenitis. In der Knochenmarkzytologie war eine reaktive Markveränderung nachweisbar. Mit dem Nachweis von 2×106/ml Genkopien wurde eine aktive EBV-Infektion gesichert. Die Bestimmung der Autoantikörper und der Nachweis typischer klinischer Symptome ergab zusätzlich den Befund eines systemischen Lupus erythematodes. In der immunhämatologischen Untersuchung waren Autoantikörper gegen alle 3Zellreihen nachweisbar. Trotz rezidivierender Infektionen initiierten wir wegen der lang anhaltenden, antikörpervermittelten Panzytopenie eine niedrig dosierte immunsuppressive Therapie mit Kortikosteroiden. Darunter kam es zu einer Normalisierung des Blutbilds, der Antikörpertiter und der EBV-Genombestimmung. A 47-year-old woman was admitted to our emergency room because of anemia and acute tonsillitis. She reported recurrent fever and a sore throat. Clinical examination and CT scans showed general lymph node swelling and liver enlargement. In the course of the disease she developed pancytopenia with neutropenic fever, pleuropneumonia, and deep vein thrombosis. The histological examination of a lymph node showed a reactive, EBV-associated lymphadenitis. The examination of the bone marrow showed an activated marrow. The diagnosis of an active EBV infection was established with 2x106/ml EBV gene copies in the blood. In addition, systemic lupus erythematosus was diagnosed because of the typical autoantibody constellation and clinical findings. The immunohematological examination showed autoantibodies against the three blood cell compartments. Because of the severe pancytopenia as a result of the EBV- and SLE-associated autoantibodies and despite recurrent infections, we initiated immunosuppressive therapy with low-dose corticosteroids. This therapy resulted in normalization of the blood counts. Anitibody levels and the EBV genome levels became negative.
    Der Internist 01/2009; 50(6):734-739. · 0.33 Impact Factor
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    ABSTRACT: Budesonide (BUD) is a steroid with a low bioavailability, which has been used for the treatment of oral manifestations of chronic GVHD (cGVHD). We retrospectively evaluated the efficacy of BUD in the treatment of gastrointestinal cGVHD. Thirteen patients (median age 47 years) receiving BUD for the treatment of cGVHD after allogeneic hematopoietic SCT for hematological malignancies were evaluated for response. Five patients had isolated gastrointestinal cGVHD and 8 patients had mild multiorgan involvement including gastrointestinal manifestations. Six patients received CYA at the time of onset of cGVHD, which was continued during treatment with BUD. Treatment consisted of BUD, with an initial daily dose of 3 x 3 mg orally. Complete resolution of cGVHD was achieved in seven patients, and one patient achieved partial remission of cGVHD. One patient achieved complete resolution of gastrointestinal cGVHD, while systemic manifestations of cGVHD remained stable. Four patients progressed on BUD. Owing to the predominantly local effect, relapse of symptoms of cGVHD after withdrawal of immunosuppression (n=3) as well as progression of GVHD at other sites (n=3) has been observed. BUD represents a treatment option in mild-to-moderate cGVHD, which is well tolerated and associated with a high response rate in gastrointestinal cGVHD.
    Bone marrow transplantation 10/2008; 42(8):541-6. · 3.00 Impact Factor
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    ABSTRACT: Liposomal cytarabine has been proven to be useful for the prevention and intrathecal treatment of neoplastic meningitis. It has no demonstrable myelosuppressive effects and may therefore be an attractive alternative for prophylaxis and treatment of the central nervous system (CNS) relapse after allogeneic haematopoietic stem cell transplantation (HSCT). The use of liposomal cytarabine had not been reported in HSCT recipients. We retrospectively reviewed the feasibility of liposomal cytarabine in the prophylaxis (n=2) and treatment (n=4) of neoplastic meningitis in a cohort of patients after allogeneic HSCT. This report focusses on neurological complications after intrathecal application of liposomal cytarabine. Mild headache was the most commonly reported adverse event. Two patients experienced sacral radiculopathy with irreversible cauda equina syndrome in one patient. Another patient progressed with pre-existing leukencephalopathy. Intrathecal liposomal cytarabine should be used very cautiously in allogeneic HSCT recipients with a history of CNS complications potentially involving cerebral-spinal fluid circulation, since significant neurotoxicity was observed in patients with extensive CNS-directed pre-treatment. The feasibility and safety of liposomal cytarabine in HSCT recipients has to be evaluated in a prospective study.
    Annals of Hematology 09/2008; 87(12):1009-12. · 2.87 Impact Factor
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    ABSTRACT: Central venous catheters (CVC) guarantee a reliable venous access and are an indispensable part of the therapy in patients with hematologic malignancies. On the other hand, they contribute significantly to the therapy-related morbidity in this group of patients. The most common complications are catheter-associated infections or thromboses. Here we report on the rare, but potentially life-threatening case of a vessel wall perforation by a CVC. A 29-year-old female with newly diagnosed acute lymphoblastic leukemia had a CVC inserted via the left subclavian vein. After two weeks she complained about acute chest pain. Radiology revealed right-sided pleural effusion which was due to a vena cava superior vessel wall perforation by the CVC. Chemotherapy extravasation was excluded by pleural fluid analyses. A vessel wall perforation by a CVC is a rare and often late CVC complication with usually unspecific symptoms. Especially patients with leftsided, large-bore catheters are at risk. Awareness of this complication and immediate therapy are essential. We discuss the possible mechanisms and treatment options of this rare CVC complication.
    Onkologie 06/2008; 31(5):262-4. · 1.00 Impact Factor
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    ABSTRACT: This study of first-line treatment in advanced-stage follicular lymphoma patients analysed the effects of MCP (mitoxantrone, chlorambucil and prednisolone) chemotherapy alone or in combination with rituximab (R-MCP) on circulating lymphoma cells (CLC) and assessed the prognostic value of a quantitative monitoring of CLC. CLC numbers were determined by quantitative polymerase chain reaction (PCR) for the t(14;18)-translocation or by allele-specific PCR for rearranged immunoglobulin heavy chain genes. We analysed blood samples from 43 patients treated in a randomized trial comparing eight cycles of MCP versus R-MCP. Clearance of CLC at the end of therapy was achieved in 21/25 patients (84%) treated with R-MCP compared with 0/18 after MCP alone (P < 0.0001). A > or = 2 log CLC reduction was associated with a favourable clinical response (P = 0.0004) and prolonged event-free survival (P = 0.02). In R-MCP patients, stable CLC numbers or consistently PCR-negative blood samples were associated with a continuing clinical remission whereas in two patients a relapse was preceded by a > or = 2 log CLC increase. This study demonstrated that R-MCP led to a rapid and sustained eradication of CLC and a > or = 2 log CLC reduction was associated with a superior quality and duration of the clinical response.
    British Journal of Haematology 05/2008; 141(5):631-40. · 4.94 Impact Factor
  • Annals of Hematology 03/2008; 87(2):155-7. · 2.87 Impact Factor
  • Value in Health 01/2008; 11(6). · 2.19 Impact Factor
  • M Angelescu, T Foitzik, M Leithäuser, F Prall, E Klar
    Zeitschrift Fur Gastroenterologie - Z GASTROENTEROL. 01/2007; 45(08).
  • Zeitschrift Fur Gastroenterologie - Z GASTROENTEROL. 01/2007; 45(08).
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    ABSTRACT: Steroid-resistant acute GVHD (aGVHD) following allogeneic hematopoietic stem cell transplantation (alloHSCT) continues to be associated with a high mortality. We report the results of a phase II study of treatment of steroid-resistant aGVHD with the IL-2 receptor antibody daclizumab combined with the TNF-receptor fusion protein etanercept. Treatment consisted of daclizumab 1 mg/kg given i.v. on days 1, 4, 8, 15, 22 and etanercept 16 mg/m(2) s.c. on days 1, 5, 9, 13, 17. A total of 21 patients (age 15-61 years) with steroid-resistant aGVHD after alloHSCT were included in the study. Donor types were HLA-matched related (n=6), HLA-matched unrelated (n=14), and HLA-mismatched unrelated (n=1). Eight patients achieved complete, and six showed partial remission of aGVHD. Seven patients did not respond. Four of 21 patients are currently alive with a median follow-up of 586 (185-1155) days. Three patients died due to relapsed malignancy. Treatment-related mortality was due to infectious complications (n=11) or organ failure due to aGVHD (n=3). In total, 12 patients developed subsequent chronic GVHD. In conclusion, the data demonstrate an acceptable response rate of the combination of daclizumab and etanercept in the treatment of steroid-resistant aGVHD. Nevertheless, long-term mortality due to infectious complications and chronic GVHD remains high.
    Bone Marrow Transplantation 06/2005; 35(10):1003-10. · 3.54 Impact Factor
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    ABSTRACT: Identification of additional prognostic factors besides karyotype is important for the improvement of the risk adapted treatment strategies in acute myeloid leukemia (AML). The aim of this study was to investigate whether other factors besides karyotype could be used as a prognostic tool in newly diagnosed AML. Biological and disease related established and potential prognostic factors were retrospectively analysed in 124 consecutive AML patients treated between 1993 and 2002 at the University hospital Rostock (Germany). One hundred patients received a potential curative intensive chemotherapy (81%), of whom 28 received an allogeneic HSCT at some point of their treatment course, 17 patients (14%) received palliative therapies and 7 patients (5%) received supportive care only. In patients that received potential curative therapies LDH >or=2000 U/l, WBC >50 GPT/l, CD34 surface expression on the AML blasts, secondary AML, unfavorable karyotype and no allogeneic HSCT at some point of treatment course were associated with unfavorable prognosis. However, in the multivariate risk factor analyses only unfavorable karyotype (p=0.012), CD34 positivity of AML blasts (p=0.046), no allogeneic HSCT (p=0.008) and first diagnosis after 1997 (p=0.025) were independent unfavourable prognostic factors. In conclusion, karyotype and CD34 expression are independent prognostic markers in newly diagnosed AML. Furthermore, receiving an allogeneic HSCT at some point of the treatment course seems to be of benefit for AML patients.
    Neoplasma 02/2005; 52(5):402-10. · 1.57 Impact Factor
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    ABSTRACT: The graft vs. leukemia (GVL) effect is one of the most important factors of anti-tumor activity after allogeneic hematopoetic stem cell transplants (alloSCT). Its effectiveness depends mainly on the tumor biology as well as the tumor burden. Patients with a high tumor burden may not respond to GVL-effect despite otherwise sensitive biology. Campath-1H is known as an effective treatment of chronic lymphocytic leukemia (CLL). Due to its ability to induce profound immunosuppression, it has also been used as part of conditioning regimens before alloSCT. We report a patient, who received campath-1H in combination with docetaxel for treatment of chemotherapy and donor lymphocyte infusion resistant CLL after alloSCT, who developed shortly after discontinuation of treatment with campath-1H severe eosinophilia of the peripheral blood and typical clinical as well as histological signs of cutaneous chronic graft vs. host disease followed by complete clearance of CLL. The clinical course demonstrates the impact of the tumor burden on the GVL-effect, as well as the effectiveness of campath-1H in the presence chemo-resistance in a patient with CLL. Furthermore, the GVL effect was not abrogated by the use of campath-1H.
    European Journal Of Haematology 03/2004; 72(2):145-8. · 2.55 Impact Factor

Publication Stats

258 Citations
119.35 Total Impact Points

Institutions

  • 2001–2011
    • University of Rostock
      • Klinik für Hämatologie, Onkologie und Palliativmedizin
      Rostock, Mecklenburg-Vorpommern, Germany
    • Fred Hutchinson Cancer Research Center
      • Division of Clinical Research
      Seattle, WA, United States