Pre-Transplant Marital Status and Hematopoietic Cell Transplantation Outcomes

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40-60 years.

The preferred type of post-remission therapy (PRT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1) is a subject of continued debate, especially in patients at higher risk of nonrelapse mortality (NRM), including patients >40 years of age. We report results of a time-dependent multivariable analysis of allogenic hematopoietic stem cell transplantation (alloHSCT) (n=337) versus chemotherapy (n=271) or autologous HSCT (autoHSCT) (n=152) in 760 patients aged 40-60 years with AML in CR1. Patients receiving alloHSCT showed improved overall survival (OS) as compared with chemotherapy (respectively, 57±3% vs 40±3% at 5 years, P<0.001). Comparable OS was observed following alloHSCT and autoHSCT in patients with intermediate-risk AML (60±4 vs 54±5%). However, alloHSCT was associated with less relapse (hazard ratio (HR) 0.51, P<0.001) and better relapse-free survival (RFS) (HR 0.74, P=0.029) as compared with autoHSCT in intermediate-risk AMLs. AlloHSCT was applied following myeloablative conditioning (n=157) or reduced intensity conditioning (n=180), resulting in less NRM, but comparable outcome with respect to OS, RFS and relapse. Collectively, these results show that alloHSCT is to be preferred over chemotherapy as PRT in patients with intermediate- and poor-risk AML aged 40-60 years, whereas autoHSCT remains a treatment option to be considered in patients with intermediate-risk AML.

Variable EBV DNA load distributions and heterogeneous EBV mRNA expression patterns in the circulation of solid organ versus stem cell transplant recipients.

UNLABELLED: Epstein-Barr virus (EBV) driven post-transplant lymphoproliferative disease (PTLD) is a heterogeneous and potentially life-threatening condition. Early identification of aberrant EBV activity may prevent progression to B-cell lymphoma. We measured EBV DNA load and RNA profiles in plasma and cellular blood compartments of stem cell transplant (SCT; n = 5), solid organ transplant recipients (SOT; n = 15), and SOT having chronic elevated EBV-DNA load (n = 12). In SCT, EBV DNA was heterogeneously distributed, either in plasma or leukocytes or both. In SOT, EBV DNA load was always cell associated, predominantly in B cells, but occasionally in T cells (CD4 and CD8) or monocytes. All SCT with cell-associated EBV DNA showed BARTs and EBNA1 expression, while LMP1 and LMP2 mRNA was found in 1 and 3 cases, respectively. In SOT, expression of BARTs was detected in all leukocyte samples. LMP2 and EBNA1 mRNA was found in 5/15 and 2/15, respectively, but LMP1 mRNA in only 1, coinciding with severe PTLD and high EBV DNA. CONCLUSION: EBV DNA is differently distributed between white cells and plasma in SOT versus SCT. EBV RNA profiling in blood is feasible and may have added value for understanding pathogenic virus activity in patients with elevated EBV-DNA.

Predictive impact of allele-matching and EBMT risk score for outcome after T-cell depleted unrelated donor transplantation in poor-risk acute leukemia and myelodysplasia.

Many parameters predict for outcome after unrelated donor (URD) allogeneic hematopoietic stem cell transplantation (alloSCT). High-resolution HLA-matching significantly impacts outcome and also the European Group of Blood and Marrow Transplantation (EBMT) risk score, based on patient age, disease stage, donor type, time from diagnosis to SCT and gender combination, may predict for non-relapse mortality and overall survival (OS). We evaluated the individual and combined effects of allele-matching and the EBMT risk score in 327 patients with poor-risk acute leukemia or myelodysplasia, who received a T-cell depleted URD alloSCT. Matching for HLA-A, -B, -C and -DRB1 alleles (8/8 match) was associated with a 5-year OS of 40% compared with 30% for mismatched (≤7/8) pairs (P=0.02). Patients with EBMT risk scores of 1-2, 3, 4 and 5-7 had 5-year OS estimates of 53, 43, 30 and 20%, respectively (P<0.001). The favorable prognostic impact of an 8/8 donor was most pronounced if the EBMT risk score was low (1-2). Five-year OS was 74±8% vs 39±11% for fully matched patients with a low-risk EBMT score as compared with EBMT low-risk patients with ≤7/8 donors. These data underscore the importance of incorporating both the EBMT risk score and the degree of high-resolution HLA-matching in the risk assessment prior to URD alloSCT.

Outcome after allogeneic transplantation for adult acute myeloid leukemia patients exhibiting isolated or associated trisomy 8 chromosomal abnormality: a survey on behalf of the ALWP of the EBMT.

The aim of this multicenter retrospective analysis was to carry out a survey of overall outcomes after allo-hematopoietic SCT of AML patients harboring trisomy 8 (+8) as the sole chromosomal abnormality or associated with other abnormalities. We have identified 182 de novo AML patients who underwent allo-hematopoietic SCT between 1990 and 2007 exhibiting isolated +8 (n=136) or +8 (n=46) associated with other favorable (n=8), intermediate (n=30), high-risk (n=7) or unknown (n=1) cytogenetic abnormalities reported to the European Group of Blood and Marrow Transplantation (EBMT). With a median follow-up of 48 months, 5-year non-relapse mortality, relapse rate, leukemia-free survival and OS were 25, 30, 45 and 47%, respectively. In a multivariate analysis, leukemia-free survival rate was improved when patients were female and transplanted in CR with an HLA-identical sibling donor. Five-year leukemia-free survival was 41, 88, 57 and 21% in patients bearing isolated +8 or +8 and other cytogenetic abnormalities of good, intermediate or poor-risk, respectively. Our retrospective data show that allo-hematopoietic SCT is an effective treatment for AML patients harboring +8. The accompanying cytogenetic abnormality to +8 seems to influence outcomes of these patients.

Stem cell-derived cardiomyocytes after bone marrow and heart transplantation.

Cardiomyocytes are a stable cell population with only limited potential for renewal after injury. Tissue regeneration may be due to infiltration of stem cells, which differentiate into cardiomyocytes. We have analysed the influx of stem cells in the heart of patients who received either a gender-mismatched BMT (male donor to female recipient) or a gender-mismatched cardiac transplant (HTX; female donor to male recipient). The proportion of infiltrating cells was determined by Y-chromosome in situ hybridization combined with immunohistochemical cell characterization. In BM transplanted patients and in cardiac allotransplant recipients, cardiomyocytes of apparent BM origin were detected. The proportions were similar in both groups and amounted up to 1% of all cardiomyocytes. The number of stem cell-derived cardiomyocytes did not alter significantly in time, but were relatively high in cases where large numbers of BM-derived Y-chromosome-positive infiltrating inflammatory cells were present. The number of Y-chromosome-positive endothelial cells was small and present only in small blood vessels. The number of BM-derived cardiomyocytes in both BMT and HTX is not significantly different between the two types of transplantation and is at most 1%.

Single-centre experience with nonmyeloablative allogeneic stem cell transplantation in patients with multiple myeloma: prolonged remissions induced.

BACKGROUND: The role of allogeneic stem cell transplantation in multiple myeloma is not yet established. METHODS: We retrospectively evaluated the outcome of nonmyeloablative allogeneic stem cell transplantation (NMA) in patients with multiple myeloma treated at the Department of Haematology of the University Medical Centre Utrecht. Thirty-six patients received NMA as part of the first-line treatment; 23 patients as part of salvage therapy. Conditioning regimen was low-dose total body irradiation (TBI, 2 Grays) only; fludarabine was added in patients without previous autologous stem cell transplantation and patients with matched unrelated donors received antithymocyte globulin in addition to fludarabine and TBI. RESULTS: Following NMA overall response increased from 84 to 90%, complete remission rate from 15 to 32%. As part of first-line treatment NMA induced complete remission in 50% of patients vs one patient (4%) treated for relapsed multiple myeloma. Median progression-free survival was 26 months (13 months for the salvage group, 38 months for the 'upfront' patients). Median overall survival has not been reached yet. The achievement of complete remission following NMA as part of first-line treatment was associated with prolonged progression-free and overall survival. Major toxicities were acute and chronic graft-vs-host disease occurring in 64% (23% grade 3-4) and in 54% (49% extensive) patients, respectively. Seven patients (12%) died from nonrelapse mortality, five patients (9%) directly related to toxicity of NMA. CONCLUSION: NMA in multiple myeloma is feasible, is associated with acceptable nonrelapse mortality and may induce prolonged complete remission. In pretreated patients the result of NMA is disappointing which urges new strategies.

Acute renal failure after allogeneic myeloablative stem cell transplantation: retrospective analysis of incidence, risk factors and survival.

Acute renal failure (ARF) is an important complication after stem cell transplantation (SCT). We retrospectively analysed ARF in 363 recipients of allogeneic myeloablative SCT to identify incidence, risk factors, associated post-transplantation complications and mortality of ARF. ARF was graded as grade 0 (no ARF) to grade 3 (need for dialysis) according to creatinine, estimated glomerular filtration rate and need for dialysis. The incidence of severe renal failure (grades 2 and 3 combined) was 49.6% (180 of 363 patients). Hypertension present at SCT was identified as a risk factor for ARF (P=0.003). Despite this, survival of these patients was not different compared to patients without hypertension. Admission to the intensive care unit (ICU) was a post-transplantation complication significantly associated with ARF (P<0.001). Survival rate was highest in patients with ARF grade 0-1 and lowest in patients with grade 3 (P<0.001). However, after correction for complications associated with high mortality (admission to the ICU, thrombotic thrombocytopenic purpura, sinusoidal occlusion syndrome (SOS) and acute graft-versus-host disease) the significant difference in survival disappeared, showing that ARF without co-morbid conditions has a good prognosis, and ARF with co-morbid conditions has a poor prognosis. This poor prognosis is due to the presence of co-morbid conditions rather than development of ARF itself.

Chimerism analysis within 6 months of allogeneic stem cell transplantation predicts relapse in acute myeloid leukemia.

The role of chimerism analysis as a prognostic indicator of relapse after hematopoietic stem cell transplantation (SCT) is controversial. We monitored chimerism status by short tandem repeat-based polymerase chain reaction (PCR) in T- and non-T-cell subsets and retrospectively evaluated clinical outcome in 96 patients with acute myeloid leukemia after myeloablative (MA) or reduced-intensity conditioning SCT. Fifty-six percent of 80 patients in the MA group demonstrated complete donor chimerism (CC) at all time points, whereas 6% had decreasing mixed chimerism (MC), 8% stable MC, 25% increasing MC and 3% increasing and decreasing MC. In 16 RIC patients, these percentages were 12, 50, 6, 6 and 19, respectively, together with 6% nonengraftment. Forty-three out of 96 patients experienced relapse. The last chimerism evaluation before relapse revealed increasing MC in only eight patients. In samples taken between 1 and 6 months post SCT, CC/decreasing MC was significantly related with a lower risk of relapse (31 versus 83%, P<0.000) and mortality (38 versus 83%, P<0.000) than with MC/increasing MC. However, the development of relapse was very rapid. Only very frequent monitoring of chimerism status by highly sensitive methods might identify impending relapse and allow early immunological intervention.

High-vs low-dose cytarabine combined with interferon alfa in patients with first chronic phase chronic myeloid leukemia. A prospective randomized phase III study.

A prospective randomized phase III study was performed to evaluate whether intensified cytarabine would induce a higher response rate and longer event-free interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML). One hundred and eighteen patients with CML in early chronic phase entered the study. Twenty-eight out of 32 patients assigned to group A received two cycles of a combination of intensified cytarabine and idarubicin followed by interferon alfa (IFN-alpha) maintenance, 28 patients in group B received standard treatment by a combination of low-dose cytarabine and IFN-alpha. Forty-nine patients with a human leukocyte antigen-identical sibling donor proceeded to allogeneic stem cell transplantation (allo-SCT) and nine patients were excluded from the analysis. Hematological response was observed in 97% of the patients in group A vs 86% of the patients in group B during the first year of treatment. In group A, 16 patients (50%) achieved a major cytogenetic response, which compared to seven patients (25%) with a major cytogenetic response in group B. With a median follow-up of 58 months (range 34-76), event-free survival was not significantly different between arms A and B. The estimated 5-year survival rate was 56% in the intensified arm and 77% in the low-dose arm (P = 0.05). Recipients of allo-SCT showed a 5-year estimated survival rate of 55%. Although intensified cytarabine induced a higher initial percentage of major and complete cytogenetic responses, responses were not sustained by IFN-alpha maintenance therapy.

Pulmonary complications after T-cell-depleted allogeneic stem cell transplantation: low incidence and strong association with acute graft-versus-host disease.

Lung injury limits the success of allogeneic stem cell transplantation (SCT). The overall incidence varies from 30 to 50% and non-infectious causes occur in one-third to one-half of these. We reviewed pulmonary complications in 369 consecutive patients who received a partially T-cell-depleted myeloablative allogeneic hematopoietic SCT at our institution between 1993 and 2003. All patients were treated uniformly with cyclophosphamide followed by total body irradiation. Control subjects were matched on sex, underlying diagnosis, age, type of transplantation and cytomegalovirus (CMV)-serostatus. Sixty-one patients (16.5%) developed pulmonary complications. Twenty-one patients (5.7%) developed infectious pneumonia. Forty patients developed non-infectious complications which were further subclassified as bronchiolitis obliterans (3.5%), bronchiolitis obliterans-organizing pneumonia (0.5%), diffuse alveolar hemorrhage (0.8%), idiopathic pneumonia syndrome (5.5%) or mixed etiology (0.5%). Acute graft-versus-host disease (GVHD) > or =grade II was significantly more common in pulmonary patients than in the controls (36/61 versus 22/61 patients, P=0.02). There was no significant difference in the incidence of chronic GVHD (P=0.09). CMV reactivation was significantly more frequent in patients with lung injury (P=0.02). Median survival was 41 weeks for the pulmonary patients and 350 weeks for the controls (P=0.001). Altogether, the incidence of pulmonary complications is low after T-cell-depleted SCT and is associated with acute GVHD and CMV reactivation.

Prognostic factors for donor lymphocyte infusions following non-myeloablative allogeneic stem cell transplantation in multiple myeloma.

In this retrospective study, we evaluated donor lymphocyte infusions given for relapsed (n=48) or persistent (n=15) myeloma following non-myeloablative allogeneic stem cell transplantation (Allo-SCT). Twenty-four of 63 patients (38.1%) responded: 12 patients (19.0%) with a partial response (PR) and 12 patients (19.0%) with a complete response (CR). Overall survival after donor lymphocyte infusions (DLI) was 23.6 months (1.0-50.7+). Median overall survival for non-responding patients was 23.6 months and has not been reached for the patients responding to DLI. In responders, progression-free survival after DLI was 27.8 months (1.2-46.2+). Patients with a PR had a median progression-free survival of 7.0 months, whereas patients with a CR to DLI had a median progression-free survival of 27.8 months. Major toxicities were acute graft-versus-host disease (GVHD) (38.1%) and chronic GVHD (42.9%). Seven patients (11.1%) died from treatment-related mortality. The only significant prognostic factors for response to DLI were the occurrence of acute and chronic GVHD. There was a trend towards significance for time between transplantation and DLI, and response. Donor lymphocyte infusion following non-myeloablative Allo-SCT is a valuable strategy for relapsed or persistent disease.

Active Epstein-Barr virus infection after allogeneic stem cell transplantation: re-infection or reactivation?

Recipients of allogeneic stem cell transplants (SCT) often show active Epstein-Barr virus (EBV) infection, which may progress to EBV-associated lymphoproliferative disorders. It is not known whether these EBV infections are true reactivations of the endogenous EBV strain or re-infections with an exogenous EBV strain. Fifty-three recipients of matched related or matched unrelated donor grafts were studied. EBV monitoring was based on a realtime TaqMan EBV DNA polymerase chain reaction (PCR) assay in plasma. In 17 patients, EBV DNA PCR monitoring was performed in peripheral blood mononuclear cells (PBMCs) as well. Mouth washings (MWs) were collected pre-transplant from all patients and family donors. Both pre-transplant EBV DNA from MWs and post-transplant EBV DNA from plasma or PBMCs were successfully obtained in 6 patients. A nested PCR targeting the EBV latent membrane protein-1 C-terminus gene was used to determine sequence variations enabling EBV strain typing. In 3 of 6 patients, the post-transplant EBV sequence pattern differed from the pre-transplant pattern, indicating a re-infection post-transplant with an exogenous strain instead of a reactivation of the original endogenous EBV strain. In the other 3 patients, the endogenous strain was identified. Active EBV infection resulting from re-infection was more severe compared with active EBV infection because of reactivation. In conclusion, active EBV infections after allogeneic SCT frequently result from re-infection with an exogenous EBV strain instead of a true reactivation of the endogenous strain and are potentially more severe.

Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma.

The feasibility and efficacy of up-front high-dose sequential chemotherapy followed by autologous stem cell transplantation (ASCT) in previously untreated adults (median age 33 years; range 15-64) with Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or lymphoblastic lymphoma (LyLy), both without central nervous system or extensive bone marrow involvement was investigated in a multicenter phase II study. Treatment consisted of two sequential high-dose chemotherapy induction courses incorporating prednisone, cyclophosphamide, doxorubicin, etoposide and mitoxantrone, without high-dose methotrexate or high-dose cytarabine. Patients with at least PR went on with BEAM and ASCT. Protocol treatment was completed by 23/27 (85%) BL/BLL and 13/15 (87%) LyLy patients. Median treatment duration until BEAM was 70 (range: 50-116) days. No toxic deaths occurred. Response to treatment was complete response (CR) 81% and partial response (PR) 11% for BL/BLL, CR 73% and PR 20% for LyLy. At a median follow-up of 61 months of patients still alive, six BL/BLL and eight LyLy patients have died. The actuarial 5-year overall and event-free survival estimates are 81 and 73% for BL/BLL vs 46 and 40% for LyLy patients. In conclusion, this short up-front high-dose sequential chemotherapy regimen, followed by ASCT is highly effective in adults with BL/BLL with limited bone marrow involvement, but less so in patients with LyLy.

The impact of donor gender on outcome of allogeneic hematopoietic stem cell transplantation for multiple myeloma: reduced relapse risk in female to male transplants.

The impact of the donor gender on outcome in HLA-identical sibling donor hematopoietic stem cell transplantation for multiple myeloma was studied in a retrospective registry study of 1312 patients (476 male to male (M --> M); 334 female to male (F --> M); 258 male to female (M --> F); 244 female to female (F --> F) reported to the European Group for Blood and Marrow Transplantation (EBMT). The best overall survival (OS) from the time of transplantation was found in F --> F (median 41 months) with no significant difference between other groups (median 25 months in M --> M, 18 months in F --> M, 19 months in M --> F) despite a significantly higher nonrelapse mortality in F --> M. This was due to a significantly lower relapse rate (REL) in F --> M compared to all other groups. Before 1994, OS was poorer in F --> M than in M --> M, which improved to similarity from 1994 onwards (median 29 months in M --> M and 25 months in F --> M). The reduced REL contributed to this improvement in F --> M indicting a gender-specific graft vs myeloma effect. Therefore, a female donor is as good as a male one for male patients, while for female patients gender disparity is a negative factor for outcome.

The importance of identifying a back-up donor for unrelated stem cell transplantation.

The importance of identifying a back-up donor, once a primary suitable unrelated stem cell donor has been found, is often underestimated. Transplant centres erroneously count on the unrelated volunteer donors to be willing, available and medically fit for actual donation. According to our data, which includes 502 unrelated donor work-up procedures performed for 425 Dutch patients between 1987 and 2002, one of 11 work-ups ended in the primary requested donor failing to donate. Of all donor-related cancellations (N=46), 78% of the procedures were deferred due to medical reasons and 22% due to nonmedical reasons. Most of the donors deferred for medical reasons were female (P=0.005). In 50% of the cases for which a back-up donor was already identified, the patients were transplanted with a delay of less then 2 weeks; when no back-up donor was available, the median delay increased to 18 weeks. We strongly encourage implementing a search for at least one back-up donor in the primary search. Identifying a back-up donor can save precious time and complicated logistic rescheduling.

Low incidence of infectious complications after nonmyeloablative compared with myeloablative allogeneic stem cell transplantation.

Allogeneic stem cell transplantation (SCT) using a myeloablative (MA) conditioning regimen is limited to relatively young patients because of increased transplant-related mortality in elderly patients. Nonmyeloablative (NMA) conditioning regimens have been developed aiming to reduce transplant mortality. In this study, we set out to evaluate the post-transplant occurrence of infectious complications in recipients of grafts from human leukocyte antigen (HLA)-identical sibling donors treated with either NMA or MA conditioning regimens. Data of 78 consecutively treated patients were analyzed. An NMA conditioning regimen was used in 40 patients and an MA regimen in 38 patients. A significantly lower rate of episodes of febrile neutropenia (0% vs. 34%, P<0.01) and post-transplant Epstein-Barr virus reactivations (0% vs. 18%, P<0.05) was found in SCT recipients treated with an NMA conditioning regimen compared with an MA conditioning regimen. Furthermore, fewer invasive fungal infections (2% vs. 12%, not significant) were diagnosed in the NMA group. The incidence of cytomegalovirus (CMV) reactivations and bacterial infections was low in both groups (CMV reactivations: 13% in both groups; bacterial infections: 10% in the NMA group vs. 8% in the MA group), while CMV disease developed in only 1 patient. Overall, compared to our MA regimen, we found a very low rate of infectious complications after NMA SCT.

[Allogeneic stem cell transplantation following non-myeloablative conditioning: favorable results in 21 high risk patients with hematological malignancies treated in the Utrecht University Medical Center, the Netherlands]. / Allogene stamceltransplantatie na niet-myeloablatieve conditionering: gunstige ervaringen bij 21 hoogrisicopatiënten met een hematologische maligniteit behandeld in het Universitair Medisch Centrum Utrecht.

OBJECTIVE: To describe the results of allogeneic stem cell transplantation after non-myeloblative conditioning in high-risk patients with a haematological malignancy. DESIGN: Prospective and descriptive. METHOD: In the Utrecht University Medical Centre 21 patients in an advanced stage of various haematological malignancies were treated with allogeneic stem cell transplantation following non-myeloablative conditioning. The patients were either younger than 55 but unsuitable for standard allogeneic stem cell transplantation because of co-existing disease, or between the ages of 55 and 70, and they had to have either a HLA-identical donor relative or a donor in which there was only one mismatched antigen. They were treated with a combination of fludarabine and a low dose of total body irradiation, followed by the administration of an unmanipulated stem cell transplantated. RESULTS: Engraftment of the stem cells was rapid in all patients but one, and 9 patients already showed complete donor cell chimerism 4 weeks after the infusion of stem cells. A total of 12 patients ultimately became completely donor chimeric, one of whom had received donor leucocytes; 7 patients were still mixed chimeric, with > 80% donor cells. 13 patients developed acute 'graft-versus-host disease' (GVHD), but in 10 of these it was mild and transitory. After a median follow-up of 9 months, 5 patients (24%) had died, 4 as a result of disease progression and one from a cause related to the transplantation. CONCLUSION: Allogeneic stem cell transplantation following non-myelaoblative conditioning is a convenient mode of therapy with a low mortality related to the transplantation. It is particularly suitable for the treatment of older patients at high risk with regard to their disease.