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1.
Leukemia ; 36(9): 2189-2195, 2022 09.
Article in English | MEDLINE | ID: mdl-35869267

ABSTRACT

Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65-80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1-24. In the second cycle, cytarabine 1000 mg/m2 twice daily, days 1-6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69-91%) vs. 59% (45-72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl ).


Subject(s)
Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Active Transport, Cell Nucleus , Aged , Antineoplastic Combined Chemotherapy Protocols , Cytarabine , Humans , Hydrazines , Triazoles
2.
Transpl Infect Dis ; 17(5): 751-5, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26432076

ABSTRACT

Multidrug-resistant (MDR) cytomegalovirus (CMV) emerged after transient responses to ganciclovir, foscarnet, and cidofovir in a CMV-seropositive recipient who underwent allogeneic hematopoietic stem cell transplantation from a CMV-seronegative donor. Experimental treatments using leflunomide and artesunate failed. Re-transplantation from a CMV-seropositive donor supported by adoptive transfer of pp65-specific T cells and maribavir was followed by lasting suppression. This case illustrates that successful MDR CMV therapy may require individualized multidisciplinary approaches.


Subject(s)
Cytomegalovirus Infections/therapy , Drug Resistance, Multiple, Viral , Hematopoietic Stem Cell Transplantation , Immunocompromised Host , Adoptive Transfer , Antiviral Agents/therapeutic use , Combined Modality Therapy , Cytomegalovirus Infections/immunology , Drug Therapy, Combination , Humans , Male , Middle Aged
3.
Bone Marrow Transplant ; 49(9): 1223-30, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25046214

ABSTRACT

Little is known of health-relevant behaviour among long-term survivors of haematological disorders treated with haematopoietic SCT. This comparative cross-sectional multicentre study aimed (1) to explore the prevalence of selected behaviours in this group and (2) to compare them with those of the general population. Self-reported data of 376 survivors (mean age: 50.4 (s.d. = 12.8); median 7 years postallogeneic SCT (interquartile range (IQR) = 8.9; range 1-33) were compared with controls derived from the Swiss Health Survey 2007 by propensity score matching. Survivors were more physically inactive (26.8% vs 12.5%; P ⩽ 0.001) and consumed fewer portions of vegetables (⩾ 3 pieces: 10% vs 21.6%; P < 0.001), fruits (⩾ 3 pieces: 6.5% vs 10.6%; P < 0.001) and fish (31.2% vs 60.9% weekly fish dish; P < 0.001). More survivors consumed dairy products daily (92.5% vs 62.9%; P < 0.001), used sun protection regularly (94.5% vs 85.3%, P < 0.001) and had received influenza vaccinations in the past year (58.4% vs 21.5%; P < 0.001); fewer survivors smoked (13.4% vs 35.4%; P < 0.001). Survivors' weekly alcohol consumption was lower (median 1.5 servings (IQR 4) vs median 4.5 (IQR 10.3); P < 0.001). Of those taking immunosuppressants, 65.7% were non-adherent. Similar to the general population, survivors experience problems executing several health-enhancing behaviours, warranting corrective interventions.


Subject(s)
Hematopoietic Stem Cell Transplantation/psychology , Transplantation, Homologous/psychology , Case-Control Studies , Cross-Sectional Studies , Female , Health Behavior , Hematopoietic Stem Cell Transplantation/methods , Humans , Male , Middle Aged , Risk Factors , Survivors , Transplantation Conditioning/methods , Transplantation, Homologous/methods
5.
Bone Marrow Transplant ; 49(1): 55-61, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24037023

ABSTRACT

Several T-cell depletion (TCD) techniques are used for haploidentical hematopoietic SCT (HSCT), but direct comparisons are rare. We therefore studied the effect of in vitro TCD with graft engineering (CD34 selection or CD3/CD19 depletion, 74%) or in vivo TCD using alemtuzumab (26%) on outcome, immune reconstitution and infections after haploidentical HSCT. We performed a retrospective multicenter analysis of 72 haploidentical HSCT in Switzerland. Sixty-seven patients (93%) had neutrophil engraftment. The 1-year OS, TRM and relapse incidence were 48 (36-60)%, 20 (11-33)% and 42 (31-57)%, respectively, without differences among the TCD groups. In vivo TCD caused more profound lymphocyte suppression early after HSCT, whereas immune recovery beyond the second month was comparable between the two groups. Despite anti-infective prophylaxis, most patients experienced post-transplant infectious complications (94%). Patients with in vivo TCD had a higher incidence of CMV reactivations (54% vs 28%, P=0.015), but this did not result in a higher TRM. In conclusion, TCD by graft engineering or alemtuzumab are equally effective for haploidentical HSCT.


Subject(s)
Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , Lymphocyte Depletion/methods , T-Lymphocytes/immunology , Adolescent , Adsorption , Adult , Alemtuzumab , Antibodies, Monoclonal, Humanized/therapeutic use , Antigens, CD19/metabolism , Antigens, CD34/metabolism , Antineoplastic Agents/therapeutic use , CD3 Complex/metabolism , Child , Child, Preschool , Female , Graft vs Host Disease , Hematopoietic Stem Cell Mobilization , Humans , Infant , Infant, Newborn , Male , Middle Aged , Neutrophils/cytology , Recurrence , Retrospective Studies , Switzerland , Transplantation Conditioning , Treatment Outcome , Young Adult
6.
Bone Marrow Transplant ; 49(1): 62-5, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24056739

ABSTRACT

A considerable number of patients undergoing allogeneic hematopoietic SCT (HSCT) develop post-transplant complications requiring intensive care unit (ICU) treatment. Whereas the indications and the outcome of ICU admission are well known, the risk factors leading to ICU admission are less well understood. We performed a retrospective single-center study on 250 consecutive HSCT patients analyzing the indications, risk factors and outcome of ICU admission. Of these 250 patients, 33 (13%) were admitted to the ICU. The most common indications for admission to the ICU were pulmonary complications (11, 33%), sepsis (8, 24%), neurological disorders (6, 18%) and cardiovascular problems (2, 6%). Acute GvHD and HLA mismatch were the only significant risk factors for ICU admission in multivariate analysis. Among patients admitted to the ICU, the number of organ failures correlated negatively with survival. Twenty-one (64%) patients died during the ICU stay and the 6-month mortality was 85% (27 out of 33). SAPS II score underestimated the mortality rate. In conclusion, acute GvHD and HLA mismatch were identified as risk factors for ICU admission following allogeneic HSCT. Both, short- and long-term survival of patients admitted to the ICU remains dismal and depends on the number of organ failures.


Subject(s)
Critical Care/methods , Hematopoietic Stem Cell Transplantation/methods , Intensive Care Units/statistics & numerical data , Leukemia/therapy , Lymphoma/therapy , Adolescent , Adult , Aged , Disease Progression , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Leukemia/mortality , Lymphoma/mortality , Male , Middle Aged , Recurrence , Respiration Disorders/etiology , Respiration Disorders/mortality , Retrospective Studies , Risk Factors , Sepsis/etiology , Sepsis/mortality , Switzerland , Transplantation Conditioning , Transplantation, Homologous , Treatment Outcome , Young Adult
7.
Ann Oncol ; 24(5): 1378-84, 2013 May.
Article in English | MEDLINE | ID: mdl-23372049

ABSTRACT

BACKGROUND: Genomic complexity can predict the clinical course of patients affected by chronic lymphocytic leukemia (CLL) with a normal FISH. However, large studies are still lacking. Here, we analyzed a large series of CLL patients and also carried out the so far largest comparison of FISH versus single-nucleotide polymorphism (SNP) array in this disease. PATIENTS AND METHODS: SNP-array data were derived from a previously reported dataset. RESULTS: Seventy-seven of 329 CLL patients (23%) presented with a normal FISH. At least one large (>5 Mb) genomic aberration was detected by SNP array in 17 of 77 patients (22%); this finding significantly affected TTT. There was no correlation with the presence of TP53 mutations. In multivariate analysis, including age, Binet stage, IGHV genes mutational status and large genomic lesion, the latter three factors emerged as independent prognosticators. The concordance between FISH and SNP array varied between 84 and 97%, depending on the specific genomic locus investigated. CONCLUSIONS: SNP array detected additional large genomic aberrations not covered by the standard FISH panel predicting the outcome of CLL patients.


Subject(s)
Chromosome Aberrations , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Female , Genotype , Humans , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Variable Region/genetics , In Situ Hybridization, Fluorescence , Male , Middle Aged , Multivariate Analysis , Oligonucleotide Array Sequence Analysis , Polymorphism, Single Nucleotide , Prognosis , Tumor Suppressor Protein p53/genetics
8.
Bone Marrow Transplant ; 48(3): 408-13, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22941381

ABSTRACT

Despite the introduction of novel drugs, cure of multiple myeloma remains rare. Allo-SCT can induce long-term remission, but randomized studies in advanced disease are lacking and the influence of novel drugs remains unclear. In our retrospective analysis of all patients with myeloma allografted in Switzerland, 95 patients were transplanted between 1988 and 2011. Most patients were heavily pre-treated, and 53% received novel drugs before transplant. In all, 51% were allografted after relapse or progression. Transplant trends changed over time with an increase in reduced intensity conditioning and unrelated donors. At the time of analysis 47 patients remained alive, with a median follow-up of survivors of 53 months. Acute GVHD II-IV and chronic GVHD (cGVHD) occurred in 49% and 53%, respectively; TRM at 5 years was 18%. Five-year OS and PFS were 51% and 29%, respectively. Patients who received transplant upfront vs after relapse had a significantly better outcome, as well as those who had a related donor and achieved CR post transplant. We found no impact of pre-treatment with novel drugs or cGVHD. Although long-term remission following allo-SCT can be achieved, GVHD and TRM remain major limitations. Our series suggests that benefit is highest when allo-SCT is used early in the disease.


Subject(s)
Multiple Myeloma/surgery , Stem Cell Transplantation/methods , Adult , Aged , Cohort Studies , Humans , Middle Aged , Retrospective Studies , Transplantation, Homologous , Treatment Outcome , Young Adult
9.
Hamostaseologie ; 32(1): 63-6, 2012.
Article in English | MEDLINE | ID: mdl-22083512

ABSTRACT

Allogeneic and autologous hematopoietic stem cell transplantations are important therapeutic options for patients with hematologic disorders. Hemostatic complications are frequent after hematopoietic stem cell transplantation with a considerable morbidity and mortality. The incidence of bleedings and thrombosis is highest in the first few weeks after transplantation, but may also occur later. However, beyond the first year of transplantation only limited data are available. In long-term survivors the risk for premature atherosclerosis increases over time after allogeneic hematopoietic stem cell transplantation and it is higher than in the age-adjusted general population and in recipients of autologous transplantation.


Subject(s)
Acute-Phase Reaction/epidemiology , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Hemorrhage/epidemiology , Hemostasis , Postoperative Complications/epidemiology , Thrombosis/epidemiology , Comorbidity , Germany/epidemiology , Humans , Prevalence , Risk Assessment , Risk Factors
12.
Infection ; 38(5): 423-6, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20602145

ABSTRACT

INTRODUCTION: Hemophagocytic syndrome represents a severe hyperinflammatory condition by activated macrophages. Leading viral triggering agents are Epstein-Barr virus (EBV), cytomegalovirus (CMV), and adenovirus. MATERIALS AND METHODS: We present a patient with Wegener's granulomatosis on azathioprine and prednisone medication, who developed a life-threatening hemophagocytic syndrome. Positive plasma polymerase chain reaction (PCR) with negative serology revealed a primary, disseminated infection with herpes simplex virus-1 as the triggering pathogen. After treatment with acyclovir, high-dose steroids, immunoglobulins, and etoposide, the patient recovered. CONCLUSION: Early diagnosis of potentially underlying infections of hemophagocytic syndrome influences the therapeutic approach. It is important to consider a variety of infectious agents, particularly in immunosuppressed individuals. The reported case emphasizes the importance of screening for herpes simplex virus 1.


Subject(s)
Herpes Simplex/virology , Herpesvirus 1, Human/isolation & purification , Lymphohistiocytosis, Hemophagocytic/virology , Acyclovir/therapeutic use , Etoposide/therapeutic use , Herpes Simplex/drug therapy , Herpes Simplex/immunology , Herpesvirus 1, Human/genetics , Humans , Lymphohistiocytosis, Hemophagocytic/drug therapy , Male , Middle Aged , Steroids/therapeutic use
13.
Int J Lab Hematol ; 32(3): 329-35, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19706066

ABSTRACT

The diagnosis of sideroblastic anemia is based on bone marrow aspiration, and the detection of ring sideroblasts (RS) in iron staining. The finding of laboratory parameters to approach this diagnosis still remains a great challenge. In this study, we analyzed the value of a specific erythrogram pattern from peripheral blood, produced by the ADVIA120 cell counter, to predict sideroblastic changes in the bone marrow. In a two step-design study, we first showed that 32/38 consecutive patients reporting > or =15% RS had such a pattern in the erythrogram. In the second step, we prospectively identified over a period of 32 months 21 patients with this typical erythrogram; 20/21 had > or =15% RS in the bone marrow. Hence, by this validation, we confirm that the erythrogram is highly predictive of RS in the bone marrow. The interpretation of the erythrogram should become daily practice in hematology to improve the efficacy to detect sideroblastic changes.


Subject(s)
Anemia, Sideroblastic , Bone Marrow/physiopathology , Erythroblasts/cytology , Adult , Aged , Aged, 80 and over , Anemia, Sideroblastic/blood , Anemia, Sideroblastic/diagnosis , Erythrocyte Indices , Female , Humans , Longitudinal Studies , Male , Middle Aged , Predictive Value of Tests , Young Adult
14.
Bone Marrow Transplant ; 45(1): 103-9, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19561651

ABSTRACT

The prognosis of patients with poor-risk or relapsed hematological malignancies is dismal. The dose intensification necessary to achieve subsequent CR is limited by the toxicity of chemotherapy. Treatment intensification with double allogeneic HSCT (dHSCT) may enhance the antileukemic effect and reduces treatment-related toxicity associated with prolonged aplasia during reinduction. We evaluated this approach in 23 patients, nine with primary refractory disease or relapse after conventional chemotherapy (group I) and 14 with relapses after allogeneic HSCT (group II). Double HSCT was feasible in all patients. At the end of the observation period, 6 of 23 (26%) patients were still alive and in remission with a median observation time of 60 months (1-153). The overall survival probability at 1 year was 41% (95% confidence interval (CI), 21-62%), transplant-related mortality (TRM) 28% (9-47%) and the incidence of relapse 42% (18-66%). The TRM in groups I and II were 22 and 36% and the relapse rate 33 and 50%, respectively. In conclusion, we have shown the feasibility of dHSCT with an acceptable TRM, irrespective of a previous allogeneic HSCT. Whether this approach offers a survival benefit for patients with poor-risk leukemias has to be tested in larger prospective trials.


Subject(s)
Hematologic Neoplasms/surgery , Hematopoietic Stem Cell Transplantation/methods , Adolescent , Adult , Aged , Child , Child, Preschool , Cohort Studies , Female , Graft vs Host Disease , Hematologic Neoplasms/mortality , Hematopoietic Stem Cell Transplantation/mortality , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Salvage Therapy , Transplantation Conditioning , Transplantation, Homologous/mortality
16.
Am J Transplant ; 9(5): 1072-80, 2009 May.
Article in English | MEDLINE | ID: mdl-19344433

ABSTRACT

ABO-incompatible kidney transplantation using immunoadsorption to remove anti-A/B antibodies has become a successful clinical practice. Since the data on the specificity of the ABO columns are controversial, the present study assessed the efficiency and specificity of the ABO immunoadsorption, the effect on total immunoglobulins and antibodies previously induced by vaccination. Anti-A/B antibodies were measured by agglutination and ABO flow cytometry, total IgG/IgM, carbohydrate- and protein-specific antibodies by nephelometry and ELISA. The first immunoadsorption not only efficiently reduced donor-specific anti-A/B IgM (81%) and IgG (56%) but also reduced compatible anti-A/B IgM (59%) and IgG (34%). The measurements of antidonor A/B antibodies by direct agglutination (IgM) or flow cytometry better represented the effective antibody levels than the indirect agglutination test (IgG). The median reduction of total IgM and total IgG levels after a single immunoadsorption was 34% and 18%, respectively. Antibodies against pneumococcus and haemophilus polysaccharide antigens were significantly reduced, whereas antitetanus and antidiphtheria protein antibodies were not affected. Intravenous immunoglobulin administration restored the protective anticarbohydrate antibody levels. In summary, immunoadsorption efficiently removed antidonor A/B antibodies, but was not specific for A/B antigens. Anti-A/B antibody levels as determined by ABO flow cytometry are useful to establish the minimal number of immunoadsorptions needed for successful ABO-incompatible transplantation.


Subject(s)
ABO Blood-Group System/immunology , Blood Group Incompatibility , Isoantibodies/blood , Kidney Transplantation/immunology , Adult , Blood Group Incompatibility/immunology , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Hemagglutination Tests , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Middle Aged , Treatment Outcome , Young Adult
17.
Internist (Berl) ; 49(11): 1379-82, 2008 Nov.
Article in German | MEDLINE | ID: mdl-18751963

ABSTRACT

Eosinophilic gastroenteritis is a rare clinical condition of unknown aetiology and heterogenic etiopathology. Important differential diagnoses are intestinal parasitic infections, hypereosinophilic syndrome, malignancies such as lymphoma and allergic diseases. The diagnosis can be made in most cases by patient history, routine laboratory testing and endoscopic biopsies or paracentesis. Patients with only mild diarrhea can be treated with antidiarrheal medications. More symptomatic patients are usually treated with corticosteroids.


Subject(s)
Abdominal Pain/diagnosis , Abdominal Pain/etiology , Eosinophilia/diagnosis , Eosinophilia/etiology , Gastroenteritis/complications , Gastroenteritis/diagnosis , Adult , Female , Humans
18.
Bone Marrow Transplant ; 39(6): 335-40, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17342158

ABSTRACT

Patients with refractory/relapsing lymphoma are rarely cured by chemotherapy. High-dose chemotherapy (HDC) for tumor debulking followed by reduced-intensity conditioning (RIC) hematopoietic stem-cell transplantation (HSCT) has been advocated as a concept. We previously treated 10 patients (group A) with BEAM chemotherapy followed by delayed RIC HSCT at day 28. We now report on the subsequent 11 patients receiving BEAM followed immediately by fludarabine/total body irradiation and allogeneic HSCT (group B), and compare the outcome to group A patients. Non-hematological toxicity before engraftment was comparable, only gut toxicity was higher in group B. Days in aplasia, days on antibiotics and length of hospital stay were significantly longer in group A. Cumulative incidence of acute (GvHD) >or=grade II and incidence of chronic GvHD were lower in group B. At last follow-up, seven patients in group A were alive, with six of them in complete remission. In group B, nine patients were alive, seven of them in complete remission. No significant difference in estimated 3-year overall survival was seen. These data challenge the initial concept of debulking first and delaying allogeneic RIC HSCT. Allogeneic HSCT with standard BEAM conditioning is a valid alternative for patients with resistant/relapsed lymphoma, which might be considered earlier in the disease course.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Lymphoma/drug therapy , Transplantation Conditioning/methods , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carmustine/administration & dosage , Cytarabine/administration & dosage , Etoposide/administration & dosage , Female , Graft vs Host Disease , Graft vs Tumor Effect , Humans , Kaplan-Meier Estimate , Male , Melphalan/administration & dosage , Remission Induction/methods , Transplantation, Homologous
20.
Bone Marrow Transplant ; 36(11): 993-1000, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16184183

ABSTRACT

We studied occurrence, risk factors and outcome of patients with transplant-associated microangiopathy (TAM) after allogeneic stem cell transplantation (HSCT). A total of 221 consecutive patients were transplanted between 1995 and 2002. TAM is defined as evidence of hemolysis and schistocytes in the first 100 days. Outcomes analyzed included TAM and overall survival. Of 221 patients, 68 had TAM. The cumulative incidence was 31 (25-38)% at 100 days. Patients with TAM had higher LDH, higher bilirubin, higher creatinine and more often neurologic symptoms. TAM was not associated with stem cell source, cyclosporine levels and was not more frequent in recent years. In multivariate analysis, risk factors for TAM included donor type, age, gender, ABO-incompatibility and acute graft-versus-host disease (aGvHD). In patients with TAM, 1-year survival was lower than in patients without TAM (27 +/- 18% for TAM with high schistocyte counts; 53 +/- 15% for TAM with low schistocyte counts; vs 78 +/- 7% in patients without TAM; P<0.0001). TAM was independently associated with mortality adjusting for donor type, age and aGvHD occurrence and severity. TAM is frequent after HSCT and is associated with mortality even after adjustment for aGvHD grade. Risk factors of TAM are similar to aGvHD. TAM may represent endothelial damage driven by donor-host interactions.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Hemolytic-Uremic Syndrome/etiology , Adolescent , Adult , Child , Child, Preschool , Erythrocytes, Abnormal , Female , Hematologic Neoplasms/complications , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/mortality , Hemolysis , Hemolytic-Uremic Syndrome/diagnosis , Hemolytic-Uremic Syndrome/mortality , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Analysis , Transplantation, Homologous , Treatment Outcome
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