[Show abstract][Hide abstract] ABSTRACT: Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 04/2013; 27(10). DOI:10.1038/leu.2013.110 · 10.43 Impact Factor
[Show abstract][Hide abstract] 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.
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.
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.
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; 21(4). DOI:10.1007/s00520-012-1634-1 · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is often performed in cases of advanced hematological diseases, but because of the associated mortality and a high risk of relapse it is life prolonging only in some patients.
Patients and methods:
A retrospective multi-center analysis of 401 patients was conducted to analyze the variables associated with outcome after alloHSCT in advanced hematological diseases. The Cox proportional hazards model was used to assess the independence of overall survival (OS) and disease-free survival (DFS) from prognostic factors in a multivariate model.
The 5-year OS and DFS were 27.3 and 21.1% respectively. Multivariate analysis showed that the underlying malignancy had a significant influence on OS and DFS (p < 0.001 and p < 0.011, respectively), whereas development of severe acute graft versus host disease (GvHD) had a negative impact on OS (p < 0.001). Development of chronic GvHD showed a trend to a better OS (p = 0.085) and DFS (p = 0.199). No impact was seen for the intensity of conditioning.
Development of chronic GvHD but not the conditioning regimen improved the outcome after alloHSCT for advanced malignancies, underlining the importance of immunological rather than cytotoxic effects.
[Show abstract][Hide abstract] 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. DOI:10.1093/annonc/mdr627 · 7.04 Impact Factor
[Show abstract][Hide abstract] 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. DOI:10.1016/S1470-2045(11)70300-X · 24.69 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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. DOI:10.1016/S1470-2045(10)70229-1 · 24.69 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: T-cell lymphomas (T-NHL) generally carry a poor prognosis. High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) are increasingly used to treat younger patients.
We treated patients <61 years with high-risk aggressive lymphoma with four to six courses of dose-escalated CHOP plus etoposide (MegaCHOEP) necessitating repeated ASCT. Outcomes of patients with mature T-NHL (excluding anaplastic lymphoma kinase-positive anaplastic large cell lymphoma) and aggressive B-NHL were compared using multivariate Cox regression analysis.
Compared with 84.4% of B-NHL patients, 66.7% of T-NHL patients were able to receive all treatments; the rates of progressive disease were 27.3% in T-NHL and 16.3% in B-NHL patients. At 3 years, event-free survival (EFS) and overall survival were significantly worse for T-NHL [25.9% confidence interval (CI) 10.4% to 41.4% and 44.5% CI 26.5% to 62.5%) than for B-NHL patients (60.1% CI 52.1% to 68.1%; P < 0.001 and 63.4% CI 55.4% to 71.4%; P = 0.016). In multivariate analysis, T-NHL was a strongly significant adverse risk factor for EFS (relative risk 2.2, P = 0.001).
MegaCHOEP for T-NHL patients was no better than other high-dose regimens and was unable to address the major problems of HDT/ASCT: neither early progressions nor early relapses were reduced. This study sheds some doubt on expectations that HDT/ASCT will significantly improve outcomes for patients with T-NHL.
Annals of Oncology 08/2009; 20(12):1977-84. DOI:10.1093/annonc/mdp211 · 7.04 Impact Factor
[Show abstract][Hide abstract] 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 06/2009; 50(6):734-739. DOI:10.1007/s00108-008-2279-5 · 0.31 Impact Factor
[Show abstract][Hide abstract] 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. · 0.31 Impact Factor
[Show abstract][Hide abstract] 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. DOI:10.1038/bmt.2008.209 · 3.57 Impact Factor
[Show abstract][Hide abstract] 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. DOI:10.1007/s00277-008-0546-0 · 2.63 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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. DOI:10.1111/j.1365-2141.2008.07101.x · 4.71 Impact Factor