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Allogeneic haematopoietic stem-cell transplantation is a potential curative therapy for otherwise fatal haematological diseases. This treatment modality is complex, burdensome, and can involve considerable or life-threatening adverse events requiring high-quality symptom control. In contrast to patients with solid tumours, the transition to end-of-life care can be abrupt if the underlying disease relapses or other severe transplantation-related complications occur. This Viewpoint elucidates the relationships between transplantation and palliative care teams and discusses why patients who have undergone transplantation might benefit considerably from early admittance to palliative care, even when the treatment goal is clearly curative. Close and early collaboration between transplantation teams and palliative care teams is clearly endorsed., Competing Interests: Declaration of interests All authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

To investigate the efficacy and toxicities of CPX-351 outside a clinical trial, we analyzed 188 patients (median age 65 years, range 26-80) treated for therapy-related acute myeloid leukemia (t-AML, 29%) or AML with myelodysplasia-related changes (AML-MRC, 70%). Eighty-six percent received one, 14% two induction cycles, and 10% received consolidation (representing 22% of patients with CR/CRi) with CPX-351. Following induction, CR/CRi rate was 47% including 64% of patients with available information achieving measurable residual disease (MRD) negativity (<10 -3 ) as measured by flow cytometry. After a median follow-up of 9.3 months, median overall survival (OS) was 21 months and 1-year OS rate 64%. In multivariate analysis, complex karyotype predicted lower response (p = 0.0001), while pretreatment with hypomethylating agents (p = 0.02) and adverse European LeukemiaNet 2017 genetic risk (p < 0.0001) were associated with lower OS. Allogeneic hematopoietic cell transplantation (allo-HCT) was performed in 116 patients (62%) resulting in promising outcome (median survival not reached, 1-year OS 73%), especially in MRD-negative patients (p = 0.048). With 69% of patients developing grade III/IV non-hematologic toxicity following induction and a day 30-mortality of 8% the safety profile was consistent with previous findings. These real-world data confirm CPX-351 as efficient treatment for these high-risk AML patients facilitating allo-HCT in many patients with promising outcome after transplantation., (© 2021. The Author(s).)

Allogeneic hematopoietic cell transplantation (allo-HCT) is increasingly used in older myelofibrosis (MF) patients, but its risk/benefit ratio compared to non-transplant approaches has not been evaluated in this population. We analyzed the outcomes of allo-HCT in 556 MF patients aged ≥65 years from the EBMT registry, and determined the excess mortality over the matched general population of MF patients ≥65 years managed with allo-HCT (n = 556) or conventional drug treatment (n = 176). The non-transplant cohort included patients with intermediate-2 or high risk DIPSS from the Spanish Myelofibrosis Registry. After a median follow-up of 3.4 years, the estimated 5-year survival rate, non-relapse mortality (NRM), and relapse incidence after transplantation was 40%, 37%, and 25%, respectively. Busulfan-based conditioning was associated with decreased mortality (HR: 0.7, 95% CI: 0.5-0.9) whereas the recipient CMV+/donor CMV- combination (HR: 1.7, 95% CI: 1.2-2.4) and the JAK2 mutated genotype (HR: 1.9, 95% CI: 1.1-3.5) predicted higher mortality. Busulfan-based conditioning correlated with improved survival due to less NRM, despite its higher relapse rate when compared with melphalan-based regimens. Excess mortality was higher in transplanted patients than in the non-HCT cohort in the first year of follow-up (ratio: 1.93, 95% CI: 1.13-2.80), whereas the opposite occurred between the fourth and eighth follow-up years (ratio: 0.31, 95% CI: 0.18-0.53). Comparing the excess mortality of the two treatments, male patients seemed to benefit more than females from allo-HCT, mainly due to their worse prognosis with non-transplant approaches. These findings could potentially enhance counseling and treatment decision-making in elderly transplant-eligible MF patients., (© 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Allogeneic stem cell transplantation (alloSCT) is a curative therapy for otherwise fatal diseases, however it is associated with a considerable morbidity and mortality. In consequence, it can be assumed that a considerable percentage of patients would benefit from high-quality palliative care (PC) during their course of disease. To assess the standard of PC in German transplant centers, a questionnaire was sent out to all German centers recognized from the EBMT membership list and the annually ZKRD report (n = 52). The response rate was not as high as expected with n = 27 (51,9%), even after reminding by phone calls or by e-mails. In brief, palliative care after allogeneic stem cell transplantation shows a wide variation in Germany. This is true for structures, processes and measures. A national standard for SCT-patients has not been established so far and there are no pre-conditions concerning palliative care after alloSCT for a certification by the EBMT according the JACIE standards. There is a considerable need for a crosslinking of alloSCT with PC. Clear standards should be established by the scientific societies concerning personnel, structure and processes.

Background: The role of high-dose chemotherapy with autologous stem cell transplantation (ASCT) in the treatment of soft-tissue sarcoma (STS) remains an unsettled issue. Prospective clinical trials failed to prove a benefit of the procedure but were limited by small and heterogeneous patient cohorts. Thus, it is unknown if ASCT may be a valuable treatment option in specific patient subgroups., Methods: The purpose of this study was to investigate the value of ASCT according to histological subtype in STS patients who were registered in the European Society for Blood and Marrow Transplantation database between 1996 and 2016., Results: Median progression-free (PFS) and overall survival (OS) in the entire cohort of 338 patients were 8.3 and 19.8 months, respectively, and PFS and OS at 5 years were 13% and 25%, respectively. Analysis of outcomes in different subgroups showed that younger age, better remission status before transplantation and melphalan-based preparative regimen were predictive of benefit from ASCT, whereas histology and grading had no statistically significant impact., Conclusions: Outcomes after ASCT compared favorably to those of recent trials on conventional chemotherapies and targeted therapies in STS, including histology-tailored approaches. ASCT, thus, should be reinvestigated in clinical trials focusing on defined patient subgroups., Competing Interests: Competing interests: None declared., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

The purpose of our study is to provide information on safety and efficacy of ibrutinib as salvage treatment after allo-HSCT for CLL. A total of 56 patients were included, 36 (64%) males; median age at transplantation was 48 years (range: 35-64) and the median number of treatment lines prior to transplantation was 3 (1-10). The median time between allo-HSCT and Ibrutinib was 30 months (range: 1-140). Overall, 40 (71%) patients responded to Ibrutinib; 23 (41%) PR, and 17 (30%) CR. At time of ibrutinib initiation, ten patients had active chronic GVHD that resolved under Ibrutinib, whilst a single patient developed limited de novo chronic GVHD on Ibrutinib. Fourteen patients discontinued ibrutinib, four because of toxicity and ten because of disease progression. Overall, 14 patients progressed (median PFS = 24 months) among them 10 died. Two-year OS and PFS probabilities were 72% (95% CI: 52-84) and 50% (95% CI: 32-66), respectively. Patients with late relapse after allo-HSCT (≥24 months) had a better PFS after ibrutinib. Our study shows that ibrutinib can be safely administered for CLL relapse after allo-HSCT, with comparable efficacy to non-transplanted patients with high-risk disease.

Introduction: BK polyomavirus can lead to hemorrhagic cystitis (BKPyV-HC) in allogeneic stem cell transplantation and therefore to increased morbidity. No causal therapy has been established yet. Cidofovir (CDV) is a nucleotide analog of cytosine that is active against various DNA viruses and it has been described for therapy of BKPyV-HC using 2 admission routes: intravenous and intravesical., Methods: We performed a systematic review regarding the comparison of intravenous or intravesical cidofovir in the treatment of BKPyV-HC following adult allogeneic stem cell transplantation. Since there is a lack of randomized controlled trials, we considered all kinds of studies for this review. Due to heterogeneity of the data, we were not able to perform a meta-analysis, so the results are shown descriptively., Results: The literature search for primary studies yielded 232 results. Finally, 9 studies where considered which included a total of 189 adult patients with BKPyV-HC after allogeneic stem cell transplantation. We could only identify retrospective studies for this review. A total of 172 patients received intravenous CDV, 17 patients received intravesical CDV, and 2 patients received CDV in both admission routes. In 68.0% of the cases, a complete response for intravenous CDV was documented and in 88.2% for intravesical CDV. Interestingly, no kidney toxicity was mentioned in intravesical CDV. 9.3% of the intravenously treated patients had renal failure., Conclusion: There is only weak evidence for the use of CDV. The intravesical admission route should be further investigated because of a good toxicity profile., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In contrast to the evidence regarding azacitidine (Aza), there is limited knowledge about the combination of decitabine (DAC) and donor lymphocyte infusions as salvage therapy for relapse after allogeneic stem cell transplantation (allo-SCT) so far. We retrospectively analyzed data of 36 patients with hematological (n = 35) or molecular relapse (n = 1) of acute myeloid leukemia (AML, n = 29) or myelodysplastic syndrome (MDS, n = 7) collected from 6 German transplant centers. Patients were treated with a median of 2 cycles DAC (range, 1 to 11). DAC was the first salvage therapy in 16 patients (44%), whereas 20 patients (56%) had previously received 1 to 5 lines of salvage therapy including 16 of them had been treated with Aza. In 22 patients (61%), a median of 2 DLI per patient (range, 1 to 5) was administered in addition to DAC. As a result, overall response rate was 25% including 6 complete remissions (CR, 17%) and 3 partial remissions (PR, 8%). Three patients within the first-line group achieved CR, while also 3 patients receiving DAC as second-line treatment reached CR including 2 patients with previous Aza failure. Median duration of CR was 10 months (range, 2 to 33) and no patient relapsed so far. The 2-year OS rate was 11% (± 6%) without any difference between first-line and pretreated patients. Incidence of acute and chronic graft-versus-host disease was 19 and 5%. Taken together, DAC exerts clinical efficacy in patients with AML or MDS relapsing after allo-SCT and is able to induce durable remissions in individual patients suggesting that DAC may be an alternative to Aza or even a second choice after Aza failure.

Background: Patients with genetically high-risk relapsed/refractory chronic lymphocytic leukemia have shorter median progression-free survival (PFS) with kinase- and BCL2-inhibitors (KI, BCL2i). Allogeneic hematopoietic stem cell transplantation (alloHCT) may result in sustained PFS, especially in younger patients because of its age-dependent non-relapse mortality (NRM) risk, but outcome data are lacking for this population., Patients and Methods: Risk factors for 2-year NRM and 8-year PFS were identified in patients < 50 years in an updated European Society for Blood and Marrow Transplantation registry cohort (n = 197; median follow-up, 90.4 months) by Cox regression modeling, and predicted probabilities of NRM and PFS of 2 reference patients with favorable or unfavorable characteristics were plotted., Results: Predictors for poor 8-year PFS were no remission at the time of alloHCT (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.1-2.5) and partially human leukocyte antigen (HLA)-mismatched unrelated donor (HR, 2.8; 95% CI, 1.5-5.2). The latter variable also predicted a higher risk of 2-year NRM (HR, 4.0; 95% CI, 1.4-11.6) compared with HLA-matched sibling donors. Predicted 2-year NRM and 8-year PFS of a high cytogenetic risk (del(17p) and/or del(11q)) patient in remission with a matched related donor were 12% (95% CI, 3%-22%) and 54% (95% CI, 38%-69%), and for an unresponsive patient with a female partially HLA-matched unrelated donor 37% (95% CI, 12%-62%) and 38% (95% CI, 13%-63%)., Conclusion: Low predicted NRM and high 8-year PFS in favorable transplant high cytogenetic risk patients compares favorably with outcomes with KI or BCL2i. Taking into account the amount of uncertainty for predicting survival after alloHCT and after sequential administration of KI and BCL2i, alloHCT remains a valid option for younger patients with high cytogenetic risk chronic lymphocytic leukemia with a well-HLA-matched donor., (Copyright © 2017 Elsevier Inc. All rights reserved.)

There are no epidemiological data on BK virus associated hemorrhagic cystitis (BKHC) in adult allogeneic stem cell transplantation in Germany available and associations with clinical conditions like GvHD are controversially discussed. Therefore, we conducted a nationwide survey among haematologists and urologists about this disease. We developed two questionnaires, one for haematologists (26 items) and one for urologists (20 items) concerning BKHC in adult allogeneic stem cell transplantation with epidemiological data and clinical implications. The survey was sent out at least three times to EBMT registered centres performing at least five transplantations a year, leading to 39 centres. The recruiting time was between January and June 2016. Total response rates were 76.9% among haematologists and 74.4% among urologists. BKHC seems to appear less frequent in this survey than it is described in the literature. Six deaths in the last 5 years due to this disease have been reported. Interestingly, haematologists as well as urologists mostly think that local therapy is most effective while 50.0% stated that there is no real effective oral or intravenous medication. Associations with other clinical conditions mentioned were heterogeneous, e.g. transplantation type, CMV reactivation, acute GvHD, nephropathy and worse clinical outcome. There was a significant discrepancy between haematologists and urologist concerning the association with acute GvHD (p = 0.004). We need prospective, multicentric clinical studies to evaluate local therapy and for developing a risk stratification model since this disease can be severe with morbidity and rarely mortality. In our opinion, this should be an interdisciplinary approach.

Background: The association of polyomaviruses BK and JC with other opportunistic infections and graft-versus-host disease (GvHD) in allogeneic stem cell transplantation is controversially discussed., Methods: We conducted a retrospective study of 64 adult patients who received their first allogeneic stem cell transplantation between March 2010 and December 2014; the follow-up time was 2 years., Results: Acute leukemia was the most frequent underlying disease (45.3%), and conditioning included myeloablative (67.2%) and nonmyeloablative protocols (32.8%). All patients received 10 mg of alemtuzumab on day -2 (20 mg in case of mismatch) as GvHD prophylaxis. Twenty-seven patients (41.5%) developed cytomegalovirus (CMV) reactivation. BKPyV-associated hemorrhagic cystitis was diagnosed in 10 patients (15.6%). Other opportunistic infections caused by viruses or protozoa occurred rarely (<10%). There was no association of BKPyV or JCPyV with CMV reactivation, Epstein-Barr virus reactivation, human herpes virus 6, or parvovirus B19 infection requiring treatment. There was a significant correlation of BKPyV-associated hemorrhagic cystitis with toxoplasmosis (p = 0.013). Additionally, there was a significant link of simultaneous BKPyV and JCPyV viruria with toxoplasmosis (p = 0.047). BKPyV and JCPyV were not associated with GvHD, relapse, or death., Conclusion: We found no association of BKPyV or JCPyV with viral infections or GvHD. Only the correlation of both polyomaviruses with toxoplasmosis was significant. This is a novel and interesting finding., (© 2017 S. Karger AG, Basel.)

Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial agents but includes recommendations on the use of vaccinations. This is the updated version of the AGHIO guideline in the field of allogeneic haematopoietic stem cell transplantation utilizing methods according to evidence-based medicine criteria.

Purpose: In patients undergoing allogeneic stem cell transplantation, conditioning regimens containing alemtuzumab instead of anti-thymocyte globulin (ATG) may result in an earlier platelet engraftment and a reduced number of platelet transfusions., Methods: We performed a retrospective, single-center, case-control study analyzing time to engraftment and transfusion needs using alemtuzumab in comparison with ATG as part of conditioning protocol., Results: Median values for time to platelet engraftment, number of transfused platelet concentrates and number of transfused red cell concentrates were 12 versus 19.5 days (p < 0.001), 2 versus 14 (p < 0.001) and 6 versus 14.5 (p = 0.003) in the alemtuzumab and ATG group. Time to leukocyte engraftment did not differ with median 15 days in both groups. Patients in the ATG group showed a significant higher decrease in platelet count during conditioning (68 vs. 29 %, p = 0.001), leading to significant lower median platelet counts at the day of stem cell infusion (38 vs. 95.5 Gpt/l, p = 0.008), and higher values for median C-reactive protein after first antibody infusion (69.0 vs. 43.6 mg/l, p = 0.001) compared with alemtuzumab group. Test for significance was done by using Wilcoxon rank-sum test. Subgroup analysis considering the type of ATG used (Thymoglobulin vs. ATG Fresenius) revealed that differences between alemtuzumab and ATG group were more due to effects of ATG Fresenius than Thymoglobulin., Conclusions: The use of alemtuzumab in comparison with ATG as part of the conditioning regimen may be an approach to reduce the number of transfused platelet and red cell concentrates after allogeneic stem cell transplantation.

Introduction: Allogeneic stem cell transplantation (alloSCT) has become available for elderly patients or for patients with comorbidities by introduction of reduced-intense conditioning. Comorbidity-related prognosis after alloSCT can be estimated by the hematopoietic cell transplantation comorbidity index (HCT-CI)., Material and Methods: The charts from 85 patients who have undergone 90 alloSCTs between 1999 and 2011 were analysed. Most patients received a dose-reduced conditioning and a graft from an unrelated donor. Patients were stratified for age, HCT-CI, cGvHD versus no cGvHD, and a modified HCT-CI with a further split high-risk score., Results: Age over 60 years did not affect the outcome. Manifestation of cGvHD improved the prognosis significantly. An additional stratification of the high-risk group of the HCT-CI revealed that even a fraction of these patients can have considerable benefit from an alloSCT. Furthermore, this high-risk collective could be clearly discriminated into two groups with different outcomes., Conclusions: The investigation confirms that age is no absolute risk factor for alloSCT and demonstrates the heterogeneity of the high-risk group of the HCT-CI. A comprehensive investigation of an additional stratification is suggested. Furthermore, the authors encourage early withdrawal of immunosuppression, even in elderly patients and patients with comorbidities to permit graft-versus-leukaemia/lymphoma, since cGvHD is associated with a significantly better prognosis.

This study was conducted in order to evaluate allogeneic stem cell transplantation (alloSCT) as consolidation for patients with mantle cell lymphoma (MCL). Patients with MCL were included into two prospective trials OSHO #060 (refractory/relapsed) and #074 (de novo). Induction was rituximab and chemotherapy. Responding patients proceeded to alloSCT. Minimal residual disease was monitored by quantitative RT-PCR detecting either t(11;14) or clonospecific CDR-III regions. In case of circulating lymphoma cells, immunomodulation (cyclosporine A withdrawal, rituximab, donor lymphocyte infusion) was initiated. Thirty-three of 39 patients underwent alloSCT after myeloablative (n = 7) or toxicity-reduced (n = 26) conditioning. Leukocytes engrafted at day +16 (median, range 0-101) and platelets at day +14 (0-142). Acute graft-versus-host disease stages I-II occurred in 42 % and stages III-IV in 15 %. Five patients have relapsed after SCT. The overall mortality after SCT was 24 % (n = 8). Median follow-up after SCT was 2.8 years (range 0.0-10.9). Five-year progression-free survival was 67 %, and overall survival 73 % after SCT. The results were comparable for primary MCL and refractory/relapsed disease as well as for related vs. unrelated SCT. Younger patients had a significantly better outcome than the elderly. AlloSCT is a feasible and promising consolidation therapy for relapsed and refractory disease and an attractive option for young patients with de novo MCL of high risk.

Antibody-mediated in vivo T cell depletion is common prior to unrelated (URD) or mismatched allogeneic stem cell transplantation (alloSCT) and optional in HLA-identical sibling (FAM) alloSCT. While anti-thymocyte globulin (ATG) is the current standard, alemtuzumab is an alternative. The optimal dose of alemtuzumab has not been defined. This retrospective analysis compares low-dose alemtuzumab with ATG in URD alloSCT and with no antibody in FAM alloSCT. Twenty-eight patients treated with alemtuzumab (10 mg; HLA mismatch, 20 mg) were matched to 28 patients who have either received ATG (URD) or no antibody (noAB) according to disease, disease stage, age, transplant type and risk state. Both groups were compared for engraftment, outcome, disease-free (DFS) and overall survival (OS), graft-versus-host disease (GvHD), freedom from GvHD (ffGvHD) and transplant-related mortality (TRM). No significant differences were found between the groups for leukocyte engraftment, GvHD, ffGvHD, TRM, DFS and OS. There was a trend for reduction of cGvHD by alemtuzumab (p = 0.05). A transplant-type stratified subanalysis consolidated equivalency of alemtuzumab and ATG in URD-SCT and indicates possible superiority of low-dose alemtuzumab compared to noAB in FAM-SCT. Low-dose alemtuzumab, as part of conditioning regimen prior to alloSCT, is safe and comparable to standard ATG. Prospective trials, particularly comparing alemtuzumab vs. noAB in FAM alloSCT, should be conducted.

More than 18,000 autolgous transplantation were performed in Europe in the year 2009. It as a routine procedure in experienced centres. Even if there is a low mortality rate, infections are a major issue after transplantation, occurring in more than 60 % of the patients. In this review we discuss all aspects of infections after autologous stem transplantation, including epidemiology, diagnostics, therapeutic algorithms, prophylaxis and supportive therapy.

Toxoplasmosis is a rare but possibly underestimated complication following allogeneic stem cell transplantation with a high mortality rate. One reason might be the limitation of the diagnostic instruments relying mainly on imaging and molecular-based techniques. In this report, we present three cases of toxoplasmosis identified among 155 allograft recipients treated at Greifswald University Hospital. Widely disseminated toxoplasmosis was detected post-mortem in two patients allografted for high-risk multiple myeloma. Clinical signs suspicious for toxoplasmosis occurred after days +32 and +75, respectively. In one case, serology and conventional Toxoplasma gondii PCR, targeting the B1 gene, revealed negative results, while in the other patient, toxoplasmosis was not investigated. Both patients received pentamidine for Pneumocystis jirovecii pneumonia (PcP) prophylaxis. The third patient, a 68-year-old woman allografted for AML, developed cerebral toxoplasmosis from day +395 after allogeneic SCT with typical signs in magnetic resonance tomography. Toxoplasma DNA was amplified from one of two samples of cerebrospinal fluid. The patient died of disseminated toxoplasmosis despite immediate initiation of therapy. Retrospective comparative testing of clinical specimens by the conventional T. gondii PCR and by a real-time PCR targeting a 529-bp genomic fragment suggests a higher sensitivity of the latter method in our patients. In conclusion, we suggest a rigorous real-time PCR monitoring for high-risk patients or patients with signs of infections suspicious for toxoplasmosis, even though low-copy results are presently difficult to interpret. Our reported cases might also encourage the use of trimethoprim-sufmethoxazole instead of pentamidine for PcP prophylaxis in those patients.

Background: Measures to prevent transfusion-transmitted cytomegalovirus (TT-CMV) infection after hematopoietic stem cell transplantation (HSCT) include transfusion of CMV antibody-negative blood units and/or transfusion of leukoreduced cellular blood products. We assessed the incidence of TT-CMV in CMV-seronegative patients receiving CMV-seronegative HSC transplants, who were transfused with leukoreduced cellular blood products not tested for anti-CMV., Study Design and Methods: In a prospective observational study between 1999 and 2009, all HSCT patients received leukoreduced cellular blood products not tested for anti-CMV. Patients were screened for CMV serostatus and CMV-negative recipients of CMV-negative transplants were systematically monitored for TT-CMV clinically and by CMV nucleic acid testing. Anti-CMV antibodies (immunoglobulin [Ig]G and IgM) were assessed after three time intervals (Interval 1, study inclusion to Day +30 after HSCT; Interval 2, Day +30-Day +100; Interval 3, after Day +100)., Results: Among 142 patients treated with allogeneic HSCT, 23 CMV-negative donor-patient pairs were identified. These 23 patients received 1847 blood products from 3180 donors. All patients remained negative for CMV DNA and none developed CMV-associated clinical complications. This results in a risk for TT-CMV per donor exposure of 0% (95% confidence interval, 0.0%-0.12%). However, 17 of 23 patients seroconverted for anti-CMV IgG, but none for anti-CMV IgM. CMV IgG seroconverters received significantly more transfusions per week than nonconverters., Conclusion: The risk of TT-CMV is low in high-risk CMV(neg/neg) HSCT patients transfused with leukoreduced blood products not tested for anti-CMV. The cause of anti-CMV IgG seroconversion is most likely passive antibody transmission by blood products., (© 2011 American Association of Blood Banks.)

Background: Therapyrelated mucositis is associated with considerable morbidity. This complication following allogeneic stem cell therapy (alloSCT) is less severe after reduced intense conditioning (RIC); however, even here it may be serious., Methods: 52 patients (male: n = 35 (67%), female: n = 17 (33%)) at a median age of 62 years (35-73 years) underwent alloSCT after RIC. Conditioning was either total body irradiation (TBI)(2Gy)/±fludarabine (n = 33, 63.5%) or chemotherapy based. Graftversushost disease (GvHD) prophylaxis was carried out with cyclosporine A ± mycophenolate mofetil (MMF). 45 patients (87%) received shortcourse methotrexate (MTX). Mucositis was graded according to the Bearman and the World Health Organisation (WHO) scale. A variety of parameters were correlated with mucositis., Results: The Bearman and WHO scales showed excellent correlation. Mucositis was significantly more severe after chemotherapybased conditioning compared to conditioning with TBI(2Gy)/±fludarabine (p < 0.002) as well as in cases with an increase in creatinine levels above the upper normal value (UNV) on day +1 after SCT (p < 0.05). Furthermore, the severity correlated with time to engraftment of leucocytes (correlation coefficient (cc) = 0.26, p < 0.02) and thrombocytes (cc = 0.38, p < 0.001)., Conclusions: The conditioning regimen and increased creatinine levels at day +1 were identified as factors predicting the severity of mucositis after RICSCT. Creatinine levels on day +1 after SCT may help identify patients at risk for severe mucositis in the further course of transplantation., (2011 S. Karger AG, Basel.)

Background: Chromosomal deletion of q13 (del q13) and plasma cell leukemia predict both a worse prognosis in myeloma. Experiences with bortezomib in plasma cell leukemia prior to allogeneic stem cell transplantation (SCT) have not yet been reported., Case Report: A 66- year-old male patient was admitted for IgA myeloma(IIIA) with del q13. The myeloma progressed to plasma cell leukemia. Bortezomib was given, free light chain (FLC) excretion decreased, and myeloma cells disappeared from blood and decreased in marrow. An unrelated, mismatched allogeneic SCT was performed. The patient was discharged after engraftment with full chimerism without signs of GvHD. FLC excretion increased, and immunosuppression was discontinued. From day +84 on, bortezomib was infused again and FLC excretion decreased rapidly. Relapse was confirmed in marrow, and bortezomib was continued. Donor lymphocyte infusions (DLI) had no effect, and a further cycle of bortezomib and thalidomide had only minor effects. On day +209, the patient died from myeloma., Conclusion: This case gives evidence for an excellent initial response of plasma cell leukemia to bortezomib, however, early relapse after SCT clearly indicates limitations of both bortezomib therapy and allogeneic SCT in high-risk myeloma. Future developments are mandatory and could include combination of bortezomib with other cytostatics and early DLI in the absence of GvHD. In addition, there is need to clarify if graft-versus-myeloma effect is diminished by bortezomib therapy after allogeneic SCT.

Relapse of a preceding fungal infection is a considerable risk during haemopoietic stem cell transplantation. The optimal secondary prophylaxis has not been found so far since the application of standard drugs is hampered by potential ineffectiveness or intolerable side effects. This investigation describes haemopoietic cell transplantation of patients with a history of invasive or systemic fungal infection (IFI). The strategy was either administration of liposomal amphotericin B as secondary prophylaxis or an early switch to liposomal amphotericin B after administration of azoles. The 43 patients had a history of proven (n = 14), probable (n = 14) and possible (n = 15) IFI. Twenty-eight patients (65%) could be discharged from the BMT ward without signs of mycosis. Transplant-related mortality was 35%. Overall, 12 fungus-related (IFI) deaths (28%) occurred. The percentage of fungus-related deaths was highest in the 'proven' group with 43% compared to 20 and 21% in the two other groups. Side effects of liposomal amphotericin B were low. A discontinuation of the drug was not necessary in any patient. Serum creatinine showed a slight increase to 128% (median) of the baseline allowing continuous administration of concomitant nephrotoxic drugs such as cyclosporin A. In conclusion, secondary prophylaxis with or early switch to liposomal amphotericin B facilitates allogeneic stem cell transplantation of patients with a history of IFI with minor side effects. However, fungal infections and transplant-related mortality remain major problems in this often heavily pretreated subgroup of patients., (Copyright 2005 S. Karger AG, Basel)

Overall, 33 patients (52%) continued treatment beyond investigator assessed PD and a total of 16 patients received additional concomitant radiotherapy and/or chemotherapy. The majority of patients experiencing PD during or after anti-PD1 treatment received additional therapies (21/37, 57%). Outcomes of anti-programmed death 1 treatment for relapsed/refractory Hodgkin lymphoma: A German Hodgkin Study Group multicentre real-world analysis. [Extracted from the article]

Haematopoietic stem-cell transplantation (HSCT) is performed mainly in patients diagnosed with malignancies or some severe congenital diseases. Significant reduction of red blood cell transfusion requirements by changing from a double-unit to a single-unit transfusion policy in patients receiving intensive chemotherapy or stem cell transplantation. Patients with PRCA can become RBC transfusion dependent for a long period, suffering an important long-term iron overload, alloimmunization and transfusion reactions [15]. [Extracted from the article]

The position of aminoglycosides within interventional antibiosis in the early phase after stem cell transplantation has not been fully clarified so far although their use can induce serious renal impairment. To investigate this question early-infection data from 152 patients undergoing 195 allogeneic and autologous stem cell transplantations were investigated. Prophylaxis and treatment of infections followed international standards; however, aminoglycosides were omitted to avoid additional risks such as ototoxicity and nephrotoxicity and increased selection of resistant pathogens. Costs were another aspect. The overall-incidence of infections was 78% (152/195) and 67 patients showed more than one episode of infection. Fever of unknown origin and bacteriaemia/septicaemia dominated the spectrum of infections. The overall-response to interventional regimen consisting of ß-lactam or carbapenem plus glycopeptides was 48%. Aminoglycosides were given in three patients in the late course of disease. Overall mortality was 15/195 (7.7%) and clearly related to infection in nine cases mostly due tomould infection. A comparison with previous published literature showed no hint for inferiority of 'aminoglycoside-free' antibiotic management in stemcell transplant patients. In conclusion, the present analysis supports the policy to omit aminoglycosides in the therapy of early infections in patients undergoing stem cell transplantation to avoid additional toxicity. [ABSTRACT FROM AUTHOR]