Influence of migrant background on patient preference and expectations in breast and gynecological malignancies (NOGGO-expression V study): results of a prospective multicentre study in 606 patients in Germany.

BACKGROUND: An effective cross-cultural doctor-patient communication is vital for health literacy and patient compliance. Building a good relationship with medical staff is also relevant for the treatment decision-making process for cancer patients. Studies about the role of a specific migrant background regarding patient preferences and expectations are lacking. We therefore conducted a multicentre prospective survey to explore the needs and preferences of patients with a migrant background (PMB) suffering from gynecological malignancies and breast cancer to evaluate the quality of doctor-patient communication and cancer management compared to non-migrants (NM). METHODS: This multicentre survey recruited patients with primary or recurrence of breast, ovarian, peritoneal, or fallopian tube cancer. The patients either filled out a paper form, participated via an online survey, or were interviewed by trained staff. A 58-item questionnaire was primarily developed in German and then translated into three different languages to reach non-German-speaking patients. RESULTS: A total of 606 patients were included in the study: 54.1% (328) were interviewed directly, 9.1% (55) participated via an online survey, and 36.8% (223) used the paper print version. More than one quarter, 27.4% (166) of the participants, had a migrant background. The majority of migrants and NM were highly satisfied with the communication with their doctors. First-generation migrants (FGM) and patients with breast cancer were less often informed about participation in clinical trials (p < 0.05) and 24.5% of them suggested the help of an interpreter to improve the medical consultation. Second and third-generation migrants (SGM and TGM) experienced more fatigue and nausea than expected. CONCLUSIONS: Our results allow the hypothesis that training medical staff in intercultural competence and using disease-related patient information in different languages can improve best supportive care management and quality of life in cancer patients with migrant status.

A role for TENM1 mutations in congenital general anosmia.

Congenital general anosmia (CGA) is a neurological disorder entailing a complete innate inability to sense odors. While the mechanisms underlying vertebrate olfaction have been studied in detail, there are still gaps in our understanding of the molecular genetic basis of innate olfactory disorders. Applying whole-exome sequencing to a family multiply affected with CGA, we identified three members with a rare X-linked missense mutation in the TENM1 (teneurin 1) gene (ENST00000422452:c.C4829T). In Drosophila melanogaster, TENM1 functions in synaptic-partner-matching between axons of olfactory sensory neurons and target projection neurons and is involved in synapse organization in the olfactory system. We used CRISPR-Cas9 system to generate a Tenm1 disrupted mouse model. Tenm1(-/-) and point-mutated Tenm1(A) (/A) adult mice were shown to have an altered ability to locate a buried food pellet. Tenm1(A) (/A) mice also displayed an altered ability to sense aversive odors. Results of our study, that describes a new Tenm1 mouse, agree with the hypothesis that TENM1 has a role in olfaction. However, additional studies should be done in larger CGA cohorts, to provide statistical evidence that loss-of-function mutations in TENM1 can solely cause the disease in our and other CGA cases.

Anti-Aspergillus immunoglobulin-G testing in serum of hematopoietic stem cell transplant recipients.

BACKGROUND: Pulmonary invasive aspergillosis (IA) is a major clinical problem in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Acquisition of IA during allo-HSCT by inhalation of spores is the rationale for the widespread use of air filtration systems. Recent data suggest that activation of fungal growth in already colonized patients is a relevant factor, and a recent study found a positive correlation of serum immunoglobulin responses against purified recombinant Aspergillus fumigatus proteins before allo-HSCT with the incidence of IA after allo-HSCT. METHODS: To investigate the clinical utility of this approach, we performed a prospective study. We used a commercially available and standardized assay for detection of anti-Aspergillus immunoglobulin-G (aA-IgG) in serum (Platelia(™) Aspergillus IgG) that has previously demonstrated high sensitivity and specificity. RESULTS: In a cohort of 104 allo-HSCT recipients, we measured aA-IgG and Aspergillus antigen serum levels before allo-HSCT, and weekly during hospital stay. Overall prevalence of possible, probable, and proven IA during hospital stay was 10%, 6%, and 0%. We found no correlation between aA-IgG levels before allo-HSCT, or after allo-HSCT, and the prevalence of IA during hospital stay. Furthermore, median aA-IgG levels did not differ between patients with history of probable or proven IA, as compared to patients without history of IA. CONCLUSIONS: Taken together, our data argue against the clinical utility of measuring aA-IgG levels for diagnosis or prediction of IA in patients undergoing allo-HSCT.

Docetaxel and capecitabine for advanced gastric cancer: investigating dose-dependent efficacy in two patient cohorts.

BACKGROUND: No comparisons of different doses of docetaxel-capecitabine in patients with advanced gastric cancer have been performed. METHODS: Patients with previously untreated metastatic/locally advanced gastro-oesophageal or gastric adenocarcinoma were enrolled in a prospective multicentre phase II trial. Two sequential cohorts received docetaxel 75 mg m(-2) (day 1) plus capecitabine 1000 mg m(-2) twice daily (days 1-14) (cohort I) or docetaxel 60 mg m(-2) (day 1) plus capecitabine 800 mg m(-2) twice daily (days 1-14) (cohort II) every 3 weeks. The primary end point was confirmed overall response rate. RESULTS: In all, 91 patients were enrolled (cohort I, n=40; cohort II, n=51) and 87 were evaluable for efficacy (n=38, 49, respectively). Overall response rate was 50.0% in cohort I and 23.5% in cohort II (exploratory analysis, P=0.014). Median times to tumour progression and overall survival were 5.6 and 10.1 months in cohort I and 3.7 and 7.2 months in cohort II, respectively. Dose reductions for docetaxel and capecitabine were required in 50.0% and 57.5% of patients in cohort I and 11.8% and 15.7% in cohort II, respectively. CONCLUSION: Starting treatment with full doses and reducing promptly seems to be the more promisingly effective strategy than starting cautiously with lower doses. Docetaxel/capecitabine 75/2000 mg m(-2) is a manageable, convenient outpatient combination with promising efficacy against advanced gastric cancer.

Trends in allogeneic haematopoietic cell transplantation for myelofibrosis in Europe between 1995 and 2018: a CMWP of EBMT retrospective analysis.

We performed a retrospective assessment of patient- and transplant-specific characteristics and outcomes for 4142 patients undergoing allogeneic haematopoietic cell transplant for myelofibrosis between 1995 and 2018 across 278 centres. Activity increased steadily across the four analysed eras (<2006, 2006-2010, 2011-2014 and 2015-2018). Median recipient age increased over time between the earliest and most recent cohort (49.4 years (range, 20.1-68) versus 59.3 years (range, 18.1-78.1). Increasing number of patients with a Karnofsky performance status <90 underwent transplant over time. Increased utilisation of matched unrelated donors was apparent (<2006, 22.5% versus 2015-18, 45.2%; p < 0.001). Decreased use of myeloablative conditioning, increased use of busulphan-based platforms and anti-thymocyte globulin was evident. Of note, rates of acute (a)GVHD grade II-IV by day +100 decreased over time (p = 0.027) as did rates of chronic (c) GVHD, predominantly extensive cGVHD (<2006, 36% (31-41%) versus 2015-18, 23% (21-25%); p = 0.001). Overall, significant factors associated with worse overall survival and non-relapse mortality (NRM) remained older age, use of donors other than matched sibling, recipient CMV seropositivity and a lower Karnofsky performance status (<90). Multivariable analysis demonstrated improvements in overall survival and reductions in relapse risk over time with stable NRM rates despite increasing numbers of older, less fit patients and use of unrelated donors.

Aspergillus galactomannan testing in patients with long-term neutropenia: implications for clinical management.

We carried out a prospective study on galactomannan enzyme immuno assay (GEI) (Platelia Aspergillus EIA, Bio-Rad) testing for diagnosis of invasive aspergillosis (IA) in serum and broncho-alveolar lavage (BAL) in 200 patients with hematological malignancies and profound neutropenia. The incidence of proven and probable IA was 6% and 5.5%, respectively. In patients with fever or pneumonia, a single-positive GEI test result (galactomannan index >or= 0.5) had excellent specificity (100%). Sensitivity was relatively low (40%) at onset of fever, but increased to 94.7% after 6 days of fever. In patients with infiltrates in chest X-ray or computed tomography scan (n = 48), GEI testing in BAL had a favorable diagnostic accuracy as compared with GEI testing in serum (sensitivity 100% versus 71%). Our findings indicate that antifungal therapy should be started immediately at onset of fever in neutropenic patients with positive GEI tests. In patients with fever refractory to broad-spectrum antibiotics (>or=6 days of fever), the high diagnostic accuracy makes GEI testing a valuable diagnostic tool and questions the common strategy to carry out antifungal treatment irrespective of diagnostic testing in this situation. Our data also show that GEI testing in BAL can be useful for early diagnosis of IA in patients with hematological malignancies and pulmonary infiltrates.

Thalidomide in newly diagnosed multiple myeloma: influence of thalidomide treatment on peripheral blood stem cell collection yield.

In a phase III randomized, multicenter study, the German-speaking Myeloma-Multicenter Group (GMMG) and the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) group investigated the influence of thalidomide (Thal) on the outcome of peripheral blood stem cell (PBSC) collection in multiple myeloma (MM) before peripheral autologous blood stem cell transplantation (ABSCT). We analyzed the data of 398 myeloma patients after induction with Thal, doxorubicin and dexamethasone (TAD) in comparison with vincristine, doxorubicin and dexamethasone (VAD) followed by mobilization with cyclophosphamide, doxorubicin, dexamethasone (CAD) and PBSC collection. Within both the study groups, patients treated with TAD showed to collect significantly fewer CD34(+) cells compared with VAD (GMMG, TAD: median 9.8 x 10(6)/kg; range 2.0-33.6; VAD: median 10.9 x 10(6)/kg range 3.0-36.0; P=0.02) (HOVON, TAD: median 7.4 x 10(6)/kg; range 2.0-33.0; VAD: median 9.4 x 10(6)/kg; range 0.0-48.7; P=0.009). However, engraftment after peripheral autologous stem cell transplantation showed no difference between Thal and VAD groups. We conclude that Thal as a part of induction regimen is associated with better response rates (GMMG-HD3: CR/PR 79%, VAD: CR/PR 58%; HOVON-50: TAD: CR/PR 81%, VAD: CR/PR 61%), but significantly affects the yield of PBSC collection. Nevertheless, the number of total CD34(+) cells collected was sufficient for double autologous transplantation in 82% of the Thal patients, with at least 2.5 x 10(6)/kg CD34(+) cells.

Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial.

The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.76, 95% confidence interval (95% CI) of 0.65-0.89, P=0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74-1.08, P=0.24). The incidence of SPM were similar between the two arms (7% each, P=0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size ⩾10%) and renal impairment at baseline (serum creatinine >2 mg dl-1) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR=1.02, P=0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.

Bloodstream infections in neutropenic patients: early detection of pathogens and directed antimicrobial therapy due to surveillance blood cultures.

Bloodstream infections (BSIs) are frequent infectious complications in neutropenic patients. In order to determine the efficacy of surveillance blood cultures (BCs) to detect BSIs prior to clinical manifestation we performed a prospective trial. One hundred patients with haematological malignancies and long-term neutropenia following intensive cytotoxic therapies were recruited. BCs were taken thrice weekly during neutropenia. Forty-two patients were diagnosed with BSI. In 18 (43%) of those patients surveillance BC results were positive and identified microorganisms prior to onset of fever. In patients with positive surveillance BCs modification of the clinical management (specific antimicrobial therapy, CVC removal) resulted in a shorter time to defervescence (median 1.5 days) compared with patients with BCs positive after onset of fever (median 3.5 days, P = 0.004). In conclusion we detected causative microorganisms in more than one-third of BSIs prior to onset of clinical manifestation. The impact of surveillance BCs on the outcome has to be assessed in randomized studies.

Reduced-toxicity conditioning with fludarabine and treosulfan prior to allogeneic stem cell transplantation in multiple myeloma.

In recent years, reduced-intensity conditioning (RIC) regimens before allogeneic stem cell transplantation (SCT) are increasingly used in patients not eligible for conventional conditioning. We did a retrospective, multicenter analysis to assess the feasibility of conditioning with fludarabine and treosulfan before allogeneic SCT in multiple myeloma patients. Thirty-four patients with a median age of 51.5 years were included in the analysis. All patients underwent myeloablation after conditioning followed by stable engraftment, and 29 of 31 evaluable patients (94%) showed early complete hematopoietic chimerism. Non-hematological toxicities were limited and encompassed mainly fever in neutropenia and infections. Grade II-IV acute and chronic graft-versus-host disease was observed in 33 and 39%, respectively. With a median follow-up of 708 days (range 60-1729 days), the median progression-free survival was 180 days. The treatment-related mortality was 10% on day 100 and 25% after 1 year. The median overall survival has not yet been reached. Our data indicate that conditioning with fludarabine and treosulfan before allogeneic SCT is feasible in intensively pretreated multiple myeloma patients and leads to stable engraftment and complete hematopoietic chimerism. Randomized trials are warranted to determine if this approach might be incorporated in an algorithm of multiple myeloma treatment.

Intensified strategies to control vancomycin-resistant enterococci in immunocompromised patients.

Increasing colonization and infection with vancomycin-resistant enterococci (VRE) in immunocompromised patients are associated with increased mortality. Despite contact precautions for VRE control, rapid limitation of its spread is often impossible. We report on a VRE outbreak in a hematologic/oncologic unit including 33 patients. Although 28 of the patients had only VRE colonization, VRE-related infection was probable in 4 patients, and VRE infection of the bloodstream occurred in 1 case. Two patients were identified by VRE screening on admission, 20 were identified by weekly routine VRE screening, and 6 were identified from specimens taken to clarify infections (eg, urine, bronchoalveolar lavage). Five individuals acquired VRE colonization as inpatients (contact patients). Multiple-locus variable-number tandem repeat analysis (MLVA) proved that the outbreak was caused by VanA gene-positive Enterococcus faecium belonging to MLVA genogroup C1(MLVA types 1, 7, 12). The outbreak strains exhibited the potential virulence factor esp(enterococcus surface protein). The outbreak was terminated within 2 months by intensified infection-control measures, including quarantine and the cohorting of patients who tested positive for VRE; however, VRE spread recurred after the measures were discontinued but was again limited by resuming the measures. We conclude that intensive infection-control strategies enable the timely termination of VRE outbreaks, even those involving VRE strains with high epidemic potential on "high-risk wards" (eg, hematologic/oncologic units). Premature discontinuation of infection-control measures may cause recurrence of the VRE spread.

Pomalidomide in myeloproliferative neoplasm-associated myelofibrosis.

Myeloproliferative neoplasm (MPN)-associated myelofibrosis is a MPN characterized by bone marrow fibrosis, cytopenias, splenomegaly and constitutional symptoms. Pomalidomide, an immune-modifying drug, is reported to improve anaemia and thrombocytopenia in some patients with MPN-associated myelofibrosis. We designed a phase 2 study of pomalidomide in patients with MPN-associated myelofibrosis and anaemia and/or thrombocytopenia and/or neutropenia. Subjects received pomalidomide 2.0 mg/day in cohort 1 (n=38) or 0.5 mg/day in cohort 2 (n=58). Prednisolone was added if there was no response after 3 months in cohort 1 and based on up-front randomization in cohort 2 if there was no response at 3 or 6 months. Response rates were 39% (95% confidence interval (CI), 26-55%) in cohort 1 and 24% (95% CI, 15-37%) in cohort 2. In a multivariable logistic regression model pomalidomide at 2.0 mg/day (odds ratio (OR), 2.62; 95% CI, 1.00-6.87; P=0.05) and mutated TET2 (OR, 5.07; 95% CI, 1.16-22.17; P=0.03) were significantly associated with responses. Median duration of responses was 13.0 months (range 0.9-52.7). There was no significant difference in response rates or duration in subjects receiving or not receiving prednisolone. Clinical trial MPNSG 01-09 is registered at ClinicalTrials.gov (NCT00949364) and clinicaltrialsregister.eu (EudraCT Number: 2009-010738-23).

Allogeneic hematopoietic cell transplantation following conditioning with 90Y-ibritumomab-tiuxetan.

Radioimmunotherapy (RIT) of relapsed lymphoma is gaining increasing importance. Especially the commercially available anti-CD20 antibody 90Y-ibritumomab tiuxetan is currently under investigation in various trials including dose escalation and autologous hematopoietic progenitor cell support. It is not clear, however, whether the implementation of this radiolabeled antibody into another treatment option for relapsed or poor risk lymphoma patients-allogeneic hematopoietic cell transplantation-interferes with or delays successful engraftment. This study reports encouraging results with 2 relapsed lymphoma patients (1 transformed marginal zone lymphoma and 1 mantle cell lymphoma) who underwent allogeneic hematopoietic cell transplantation from HLA-matched donors. The conditioning regimen consisted of Rituximab 250 mg m(-2) on days -21 and -14, 0.4 mCi kg(-1) body weight 90Y-ibritumomab tiuxetan on day -14 and fludarabine (30 mg m(-2)) plus cyclophosphamide (500 mg m(-2)) on days -7 to -3. The data demonstrate that engraftment is fast and reliable with leukocytes >1 x 10(9) L(-1) on day 12 and platelets >50 x 10(9) L(-1) on day 10. Thus, the incorporation of radioimmunotherapy into allogeneic transplant protocols combines established modalities with proven anti-lymphoma activity and, hence, offers an attractive new therapeutic option for relapsed lymphoma patients.

Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma.

We aimed at demonstrating non-inferiority of bortezomib/cyclophosphamide/dexamethasone (VCD) compared to bortezomib/doxorubicin/dexamethasone (PAd) induction therapy with respect to very good partial response rates or better (⩾VGPR) in 504 newly diagnosed, transplant-eligible multiple myeloma patients. VCD was found to be non-inferior to PAd with respect to ⩾VGPR rates (37.0 versus 34.3%, P=0.001). The rates of progressive disease (PD) were 0.4% (VCD) versus 4.8% (PAd; P=0.003). In the PAd arm, 11 of 12 patients with PD had either renal impairment (creatinine ⩾2 mg/dl) at diagnosis or the cytogenetic abnormality gain 1q21, whereas no PD was observed in these subgroups in the VCD arm. Leukocytopenia/neutropenia (⩾3°) occurred more frequently in the VCD arm (35.2% versus 11.3%, P<0.001). Neuropathy rates (⩾2°) were higher in the PAd group (14.9 versus 8.4%, P=0.03). Serious adverse events, both overall and those related to thromboembolic events, were higher in the PAd group (32.7 versus 24.0%, P=0.04 and 2.8 versus 0.4%, P=0.04). Stem cell collection was not impeded by VCD. VCD is as effective as PAd in terms of achieving ⩾VGPR rates with fewer PD and has a favorable toxicity profile. Therefore, VCD is preferable to PAd as induction therapy.

The not-so-benign Miller Fisher syndrome: a variant of the Guilain-Barré syndrome.

Two patients with Fisher's syndrome of ophthalmoplegia, ataxia, and areflexia experienced severe weakness and respiratory distress. Both patients required tracheostomy and assisted ventilation, but both made a complete recovery. Fisher's syndrome is generally considered to be a benign variant of acute infectious polyneuropathy (the Guillain-Barre syndrome). Our two patients demonstrate that the condition is not always benign.

A comparative study of peripheral blood stem cell vs bone marrow transplantation from unrelated donors (MUD): a single center study.

Peripheral blood stem cell transplants (PBSCT) from unrelated donors (n = 37) were compared with bone marrow transplants (BM, bone marrow group, n = 37) in a matched pair analysis. Ten patients (2, class 1) in the alloPBSCT group and seven patients (2, class 1) in the BM group had one HLA locus mismatch donor, respectively. The following factors were matched: HLA-compatibility, diagnosis, disease stage, age and gender. The median age in the PBSC group was 37 years (19-56, excluding one 6-year-old child) and in the BM group 37 years (18-53). The BM group consisted of 12 females and 25 males, 17 females and 20 males were in the PBSC group. Twelve patients in the BM and 11 patients in the PBSC group were diagnosed with AMI,; 7/7, ALL; 15/15, CML; 2/3, MDS; 1/1, NHL. Thirty-four (14/20) of the 74 patients (45%) were considered as high risk patients. The conditioning regimen was BU/CY for standard risk patients with myeloid diseases (31 patients) and TBI/CY for ALL and NHL patients (36 patients); six patients received intensified conditioning with VP16 (2 patients), thiotepa (2 patients) or melphalan (1 patient). The GVHD prophylaxis regimen was used according to the Seattle protocol. DFS was 51% (19 patients) with a median of 352 days and 59% (21 patients) with a median of 760 days, in PBSC and BM transplants, respectively. The median time to leukocyte engraftment in PBSC patients was 14 days (range 6-26 days) and in the BM group 19 days (range 9-29 days; P < 0.02). The time of platelet engraftment did not differ significantly between the groups. The incidence of grade II-IV acute GVHD was 40% (four patients died, 13%) in the PBSC group and 20)% (three patients died, 8%) in the BM group, respectively (P < 0.05, log-rank). No signs of aGVHD were found in 19% of the patients in the PBSC and 27% in the BM group. Our results indicate that allogeneic PBSCT does lead to a significantly faster leukocyte engraftment. The significant increase with regard to the incidence and shorter time of onset of severe aGVHD in PBSC patients, compared to marrow transplant patients, need to be confirmed in a randomised trial.

New strategies in the treatment of graft-versus-host disease.

GVHD continues to be a major complication after allogeneic hematopoietic stem cell transplantation even when the recipient is given immunosuppression for the prophylaxis of this severe disease. There have been many advances in the prevention and treatment of GVHD, using compounds such as cyclosporine, FK506, mycophenolate mofetil or monoclonal IL-2 receptor antagonist. New strategies seem to include sequential therapy involving the blocking of both endogenous cytokines and alloreactive donor cells. However, further clinical and laboratory studies are needed in order to improve the therapy of established GVHD.

Lenograstim-mobilized peripheral blood progenitor cells in volunteer donors: an open label randomized split dose escalating study.

Mobilization of peripheral blood cell progenitor cells was investigated in 36 healthy sibling donors using three different split doses of glycosylated rhG-CSF (lenograstim). The donors were randomized into three groups: group 1 was given lenograstim at 8, group 2 at 11 and group 3 at 15 micrograms/kg/day in two split doses, subcutaneously for 4 and 5 days, respectively. Leukapheresis was performed on day 4 or 5 depending on the WBC and CD34+ cell count. We were able to demonstrate that there was a significant correlation between circulating CD34+ cells on the day of harvest and CD34+ cells in the apheresis products in all three groups. The number of CD34+ cells pre-apheresis was inversely correlated with age in group 1 and group 2. However, in group 3, the number of CD34+ cells pre-apheresis did not correlate with age. There was also a difference between the number of progenitor cells mobilized in the three dose groups regarding the time of harvest. Apheresis was performed in groups 1 and 2 on day 5 of mobilization in order to obtain a sufficient number of stem cells for allogeneic transplantation. In contrast, with the split dose of 15 micrograms/kg/day, harvest could be routinely performed on day 4 of stimulation. We conclude that lenograstim given twice a day at doses of 8, 11 and 15 micrograms/kg/day provided different CD34+ cell yields in normal donors, in particular, with regard to the time of harvest. The number of CD34+ cells pre-apheresis was not correlated with age in the group of donors mobilized with a split dose of 15 micrograms/kg/day, indicating that this dosage might also be suitable for older donors.

Second allogeneic hematopoietic stem cell transplantation as treatment for leukemia relapsing following a first transplant.

We report 27 patients with relapsed acute or chronic leukemia who underwent a second hematopoietic stem cell transplant (HSCT) from a related or unrelated donor. Seventeen patients were diagnosed with acute myelogenous leukemia (AML), six with acute lymphocytic leukemia (ALL) and four with chronic myeloid leukemia (CML). Ages ranged from 22 to 49 years (median 37); 13 patients were female and 14 male. Relapse was diagnosed between 1 and 45 months after the first HSCT. Sixteen patients who relapsed had received an autologous transplant initially and 11 an allogeneic transplant. Ten patients relapsed within 6 months and 17 patients later than 6 months. Chemotherapy was used as reinduction for relapse after HSCT in 16 patients who had received an autologous transplant and in three who had received an allogeneic transplant, since the latter did not respond to reduction of immunosuppression to induce a graft-versus-leukemia (GVL) reaction. Five of these 19 patients (26%) achieved complete remission (CR), seven patients did not respond to chemotherapy and seven achieved a partial remission (PR). The stem cell source for the second HSCT included bone marrow (n = 12) and PBSC (n = 4) from genotypically identical unrelated donors, PBSC (n = 7) and bone marrow (n = 3) from related donors. Currently eight of the 27 patients are alive and disease-free after the second HSCT. One patient is alive and disease-free after two allogeneic transplants (day +1538), eight patients, who relapsed after an autologous transplant followed by an allogeneic transplant (days +248 to +1140), acute myeloid leukaemia (n = 6) and chronic myeloid leukemia (n = 2) are alive and disease-free. The overall disease-free survival is 30% (8/27). The overall disease-free survival of autologous transplant patients subsequently undergoing an allogeneic transplant is 43% (P = 0.049). It is suggested that a second HSCT is possible for patients with leukemia relapse following the first autologous transplant. A second transplant might also be offered to patients relapsing after the first allogeneic HSCT. Bone Marrow Transplantation (2000) 25, 41-45.

A second unrelated bone marrow transplant with an unrelated donor marrow: treatment of a patient with relapsed leukemia.

A second bone marrow transplant might be considered as an option in patients with leukemia relapsing after bone marrow transplantation. We report the successful treatment of a patient with relapsed ALL with a second BMT from the same unrelated donor. We evaluated the usefulness of an unrelated donor as the source of the second BMT in this clinical setting. The conditioning regimen for the first transplantation consisted of BU and CY while fractionated TBI and CY were used for the second BMT. Acute skin GVHD, grade III which developed after second BMT, was successfully treated with the use of a new immunosuppressive drug, mycophenolate mofetil. Hemorrhagic cystitis and a CMV infection developed as complications during the second BMT and were successfully treated. The patient was alive and well after the second BMT with limited chronic skin GVHD up to day +170.