Factors associated with changes in quality of life in patients undergoing allogeneic haematopoietic stem cell transplantation.

It is well known that patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) experience changes in quality of life. We investigated factors associated with quality of life changes in adult HSCT patients. The Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) scale, supplemented with the Functional Assessment of Chronic Illness Therapy - Spiritual Well-being (FACIT-Sp) subscale, was administered on three occasions, immediately before transplantation, 100 days and 12 months after transplantation. Analyses of nine selected factors were made where changes in quality of life were found. Seventy-five patients were included and 40 of these completed the study. Emotional well-being was found to improve between the baseline and 100 days, while all other dimensions deteriorated, including overall quality of life. Physical and social/family well-being deteriorated between the baseline and the 12-month follow-up, while emotional well-being improved. The main factors associated with deteriorating quality of life over time were found to be significant infections, female gender and transplantation with stem cells from a sibling donor. In our further studies we aim to focus on the relationships between patients and sibling donors in order to improve the care. Careful attention must be paid to continuous adequate information during the transplantation procedure.

Allogeneic hematopoietic stem cell transplantation for advanced mycosis fungoides and Sézary syndrome. An updated experience of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option in advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS). This study presents an updated analysis of the initial experience of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT) describing the outcomes after allo-HSCT for MF and SS, with special emphasis on the impact of the use of unrelated donors (URD). METHODS AND PATIENTS: Eligible for this study were patients with advanced-stage MF or SS who underwent a first allo-HSCT from matched HLA-identical related or URD between January/1997 and December/2011. Sixty patients have been previously reported. RESULTS: 113 patients were included [77 MF (68%)]; 61 (54%) were in complete or partial remission, 86 (76%) received reduced-intensity protocols and 44 (39%) an URD allo-HSCT. With a median follow up for surviving patients of 73 months, allo-HSCT resulted in an estimated overall survival (OS) of 38% at 5 years, and a progression-free survival (PFS) of 26% at 5 years. Multivariate analysis demonstrated that advanced-phase disease (complete remission/partial remission >3, primary refractory or relapse/progression in patients that had received 3 or more lines of systemic treatment prior to transplant or the number of treatment lines was not known), a short interval between diagnosis and transplant (<18 months) were independent adverse prognostic factors for PFS; advanced-phase disease and the use of URDs were independent adverse prognostic factors for OS. CONCLUSIONS: This extended series supports that allo-HSCT is able to effectively rescue over one third of the population of patients with advanced-stage MF/SS. High relapse rate is still the major cause of failure and needs to be improved with better strategies before and after transplant. The negative impact of URD is a matter of concern and needs to be further elucidated in future studies.

Cytogenetic evolution patterns in CML post-SCT.

The cytogenetic evolution patterns in chronic myeloid leukemia (CML) after allogeneic (allo) stem cell transplantation (SCT) are different from the ones observed in non-transplanted patients, a phenomenon suggested to be caused by the conditioning regime. We reviewed 131 CMLs displaying karyotypic evolution after SCT (122 allo, nine autologous (auto)), treated at Lund University Hospital or reported in the literature. Major route abnormalities (i.e., +8, +Ph, i(17q), +19, +21, +17 and -7) were seen in 14%, balanced aberrations in 61%, hyperdiploidy in 19%, pseudodiploidy in 79%, divergent clones in 14%, and Ph-negative clones in 21%. The breakpoints involved in secondary structural rearrangements clustered at 1q21, 1q32, 7q22, 9q34, 11q13, 11q23, 12q24, 13q14, 17q10 and 22q11. Cytogenetic abnormalities common in AML after genotoxic exposure, that is, der(1;7)(q10;p10), del(3p), -5, del(5q), -7, -17, der(17p), -18, and -21, were only rarely seen post-SCT. Comparing the cytogenetic features in relation to type of SCT revealed that balanced aberrations were significantly more common after allo than after auto SCT (64 and 22%, respectively, P=0.03). In addition, there was a trend as regards hyperdiploidy being more common after auto (P=0.07) and pseudodiploidy being more frequent after allo SCT (P=0.09). Possible reasons for these differences are discussed.

Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation in Sweden, long-term results from all patients treated in 1994-2009.

High-dose melphalan and autologous stem cell transplantation (HDM/ASCT) is widely used in immunoglobulin light chain (AL) amyloidosis, but the benefit is debated mainly because of the high treatment-related mortality (24% in a randomised study comparing HDM/ASCT with oral melphalan/dexamethasone). We report here on the long-term outcome of all patients treated with HDM/ASCT for AL amyloidosis in Sweden between 1994 and 2009. Seventy-two patients were treated at eight Swedish centres. Median follow-up was 67.5 months. At least partial response (organ or haematological) was seen in 64% of the patients. Median overall survival was 98 months or 8.2 years, with 5-year survival 63.9% and 10-year survival 43.4%. In patients with cardiac involvement or multiple organ involvement, survival was significantly shorter, median overall survival 49 and 56 months, respectively. All mortality within 100 days from ASCT was 12.5% for all patients and 17.2% in the patients with cardiac involvement. For patients treated in the earlier time period (1994-2001), 100-day mortality was 23.8% compared with 7.8% in the later period (2002-2009). In conclusion, long survival times can be achieved in patients with AL amyloidosis treated with HDM/ASCT, also in smaller centres. Early mortality is high, but with a decreasing trend over time.

Value and limitations of transesophageal echocardiography in determination of left ventricular volumes and ejection fraction.

Several formulas exist for estimating left ventricular volumes and ejection fraction using conventional two-dimensional echocardiography from transthoracic views. Transesophageal imaging provides superior resolution of endocardial borders but employs slightly different scan planes. The estimation of left ventricular volumes by transesophageal echocardiography has not been validated in human patients. Therefore, the purpose of this study was to compare left ventricular volumes and ejection fraction derived from transesophageal short-axis and four-chamber images with similar variables obtained from ventriculography. End-diastolic and end-systolic volumes and ejection fraction were calculated using modified Simpson's rule, area-length and diameter-length models in 36 patients undergoing left ventriculography. Measurements of left ventricular length were obtained from the transesophageal four-chamber view and areas and diameters were taken from short-axis scans at the mitral valve, papillary muscle and apex levels. Data from transesophageal echocardiographic calculations were compared with end-diastolic volume (mean 172 +/- 90 ml), end-systolic volume (mean 91 +/- 74 ml) and ejection fraction (mean 52 +/- 15%) from cineventriculography using linear regression analysis. The area-length method (r = 0.88) resulted in a slightly better correlation with left ventricular end-diastolic volume than did Simpson's rule (r = 0.85) or area-length (r = 0.84) formulas. For end-systolic volume, the three models yielded similar correlations: Simpson's rule (r = 0.94), area-length (r = 0.93) and diameter-length (r = 0.95). Each of the methods resulted in significant underestimation of diastolic and systolic volumes compared with values assessed with angiography (p less than 0.003). Ejection fraction was best predicted by using the Simpson's rule formula (r = 0.85) in comparison with area-length (r = 0.80) or diameter-length (r = 0.73) formulas. Measurements of left ventricular length by transesophageal echocardiography were smaller for systole (mean 5.7 +/- 1.6 cm) and diastole (mean 7.7 +/- 1.2 cm) than values by ventriculography (mean 9.2 +/- 1.4 and 8.1 +/- 1.6 cm, respectively; p less than 0.0001), suggesting that underestimation of the ventricular length is a major factor contributing to the smaller volumes obtained by transesophageal echocardiography. In conclusion, currently existing formulas can be applied to transesophageal images for predicting left ventricular volumes and ejection fraction. However, volumes obtained by these models are significantly smaller than those obtained with angiography, possibly because of foreshortening in the transesophageal four-chamber view.

T lymphocytes downregulate granulocyte-macrophage colony-stimulating factor secretion from stimulated monocytes by increasing the secretion of monocyte-derived interleukin-10.

In previous studies we characterized the cytokine regulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) secretion by endothelial cells and monocytes and found differences in secretion pattern within and between these cell systems. In this study, the regulatory effect of T lymphocytes on CSF secretion was examined. T lymphocytes had no effect on CSF secretion by endothelial cells. In contrast, the addition of T lymphocytes significantly and dose dependently downregulated GM-CSF, but not G-CSF, secretion by monocytes. In one of our previous studies it was shown that interleukin-4 (IL-4) and interleukin-10 (IL-10) were the most potent inhibitory cytokines of CSF secretion by monocytes. Both these cytokines are produced by T lymphocytes. However, the downregulating effect on monocyte GM-CSF secretion was not due to increased secretion of T-lymphocyte-derived IL-4 or IL-10. Instead, the presence of T lymphocytes increased the secretion of monocyte-derived IL-10. It was shown earlier than IL-10 regulates CSF secretion by monocytes in an autocrine manner. Our data indicate that T lymphocytes might interfere with this autocrine regulation and thereby influence monocyte function in immune response and cell proliferation.

IL-10 as an autocrine regulator of CSF secretion by monocytes: disparate effects on GM-CSF and G-CSF secretion.

In previous studies of endogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) production, we found several differences in the secretion pattern within and between different cell systems; for example, CSF secretion by endothelial cells is not affected by any major downregulatory factors, whereas monocyte CSF secretion is modulated by several mechanisms. In this study, we characterized the factors that inhibit CSF secretion by monocytes. Three cytokines have inhibitory effects: interleukin (IL)-4, IL-10, and IL-13. Among these, IL-4 and IL-10 have higher potency than IL-13. IL-4 and IL-13 affect GM-CSF and G-CSF secretion to the same extent. In contrast, exogenously added IL-10 has a stronger inhibitory effect on GM-CSF secretion than on G-CSF secretion. We also found that monocytes produce IL-10 with an autocrine downregulatory effect, and that this autocrine IL-10 reaches concentrations at which in most cases only GM-CSF (not G-CSF) secretion is significantly affected. We postulate that the disparate effect of IL-10 on monocyte secretion of the two CSFs reflects their physiological functions, with GM-CSF being mainly a proinflammatory cytokine working in the local compartment and G-CSF functioning mainly as a cell recruiting factor.

Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT. A phase-2 trial.

Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib included in the conditioning regimen along with the HDM. Median progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS) after start of reinduction therapy were 21.6, 22.8 and 46.6 months, respectively. For 49 patients who completed salvage bortezomib-HDM(II) with ASCT, there was no significant difference of PFS and TNT after HDM (II) compared with after the initial HDM(I), and thus patients were their own controls (PFS (I: 20.1 vs II: 19.3 months (P=0.8)) or TNT (I: 24.4 vs II: 20.7 months (P=0.8)). No significant differences in the response rates after salvage ASCT compared with the initial ASCT. Bortezomib-HDM conditioning combo was feasible, and toxicity was as expected for patients treated with bortezomib and ASCT. In conclusion, in bortezomib-naïve patients treated at first relapse with salvage ASCT including bortezomib, PSF and TNT did not differ significantly from initial ASCT and median OS was almost 5.5 years with acceptable toxicity. A recent prospective randomized study confirms salvage ASCT to be an effective treatment.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in serum in bone marrow transplanted patients.

Colony-stimulating factors (CSF) are being increasingly used to accelerate hematopoietic recovery after bone marrow transplantation. To study the endogenous serum levels of CSF in bone marrow transplanted patients we have used immunoassays measuring granulocyte-macrophage colony-stimulating factor (GM-CSF) with a sensitivity of 0.10 ng/ml and granulocyte colony-stimulating factor (G-CSF) with a sensitivity of 0.05 ng/ml. Serum samples, taken from the conditioning treatment until engraftment, were analysed in 13 patients receiving allogeneic transplants and in eight patients receiving autologous transplants. Ten patients had acute myeloid leukemia, seven acute lymphoblastic leukemia, one acute undifferentiated leukemia, two non-Hodgkin's lymphoma and one multiple myeloma. Samples were taken 1-2 times before transplantation and 1-2 times per week after transplantation (median of 46 days in allotransplant recipients and 32 days in autotransplant recipients); 17% of the allogeneic transplanted patients and 35% of the autologous transplanted patients had detectable levels of G-CSF. In both types of transplantation the G-CSF concentrations were low: median 0.06 (range 0.05-0.14) and 0.08 (range 0.05-0.40) ng/ml respectively. GM-CSF was detected only in one analysed sample in all patients. There was no evidence of increased CSF levels related to engraftment or documented infections.

Autologous del(20q)-positive erythroid progenitor cells, re-emerging after DLI treatment of an MDS patient relapsing after allo-SCT, can provide a normal peripheral red blood cell count.

A 54-year-old RhD-negative male with del(20q)-positive myelodysplastic syndrome was transplanted with bone marrow from an HLA-identical RhD-positive sibling donor. Cytogenetic relapse was detected 21 months after stem cell transplantation (SCT), with reappearance of the original del(20q)-positive clone and reversion to recipient RhD-negative blood group. The patient received sequential donor lymphocyte infusions (DLIs), resulting in mild graft-versus-host disease and pure red cell aplasia. At 2 years post DLI, the patient remains in a stable condition, despite a dominance of recipient-derived erythro- and granulopoiesis originating in del(20q)-carrying progenitor cells. We conclude that reappearance of autologous erythropoiesis, upon relapse after allogeneic SCT, may be predictive of erythropenia after DLI and that re-emerging autologous del(20q)-positive erythropoiesis post DLI can provide a normal peripheral red blood cell count. Furthermore, in patients relapsing after blood-group-mismatched transplantation, a possible reversion to recipient blood group should be considered prior to blood transfusion or DLI.

No prevention of cytomegalovirus infection by anti-cytomegalovirus hyperimmune globulin in seronegative bone marrow transplant recipients. The Nordic BMT Group.

A randomized multicentre study was conducted to evaluate the effect of anti-CMV hyperimmune globulin in the prophylaxis of CMV infections in CMV seronegative allogeneic BMT patients who received a transplant from a seropositive donor or who had received blood products unscreened for CMV during the treatment before BMT. Twenty-eight patients were included in the study. Thirteen were randomized to receive and 15 not to receive intravenous CMV hyperimmune globulin. A dose of 0.4 g/kg of immunoglobulin was given on day -8 and 0.2 g/kg on days -1, +7, +14, +21, +28, +35, +42, +56 and +70 in relation to the day of transplantation. Among the 15 patients not given immunoglobulin CMV was isolated in three, and two of them developed clinical CMV disease. In addition, one more patient developed CMV antibodies without virus isolation. In five of the 13 patients given immunoglobulin the virus could be isolated, and four of them developed CMV disease. One additional patient showed seroconversion but no other findings of CMV infection. The incidence of acute and chronic GVHD was similar in the two arms. There was no significant difference in survival. In conclusion, the present results do not indicate a beneficial effect of CMV hyperimmune globulin infusions in the prophylaxis of CMV infection or disease in seronegative allogeneic bone marrow transplant recipients from a seropositive donor.

Alpha-interferon maintenance treatment is associated with improved survival after high-dose treatment and autologous stem cell transplantation in patients with multiple myeloma: a retrospective registry study from the European Group for Blood and Marrow Transplantation (EBMT).

The purpose of this study was to evaluate the effect of alpha-IFN maintenance treatment after autologous stem cell transplantation (ASCT) for multiple myeloma in a retrospective registry analysis. 473 patients with multiple myeloma who received IFN maintenance treatment ASCT were compared with 419 patients who did not receive IFN-treatment. Patients who were evaluable for response and in complete or partial remission at 6 months after ASCT were eligible, after excluding patients with graft failure. Cox proportional hazards assumptions were checked and handled by stratification. The prognostic variables unevenly distributed between the two groups were statistically corrected for in the Cox analysis. 391 patients reached complete remission (CR) after ASCT (203 in the IFN group and 188 in the no-IFN group) and 501 were in partial remission (PR, IFN 270, no-IFN 231). Overall survival (OS) and progression-free survival (PFS) were significantly better in the IFN-group (OS, 78 vs 47 months, P = 0.007, and PFS, 29 vs 20 months, P = 0.006, respectively). The difference in OS and PFS was most strongly pronounced in the PR patients. 209 patients have died (IFN, 84; no-IFN, 125). Progressive myeloma was the cause of death in 94% of the IFN-treated patients and in 83% of the no-IFN group (P = NS). Thus, IFN maintenance treatment after ASCT was associated with better OS and PFS. Treatment seemed to be most beneficial in patients who did not achieve CR. The difference in median survival was as long as 2.5 years, and although part of this difference is attributable to differences in other prognostic factors, it might justify possible differences in quality-of-life due to adverse effects of interferon treatment.

Comparison of transesophageal color flow Doppler imaging of normal mitral regurgitant jets in St. Jude Medical and Medtronic Hall cardiac prostheses.

Transesophageal color flow Doppler imaging of mitral mechanical prostheses is now widely used. This method eliminates the frequent problems of acoustic shadowing and flow masking that are commonly seen with a transthoracic Doppler study of mechanical mitral prostheses. Transesophageal color flow Doppler imaging was performed postoperatively in seven patients who had received St. Jude Medical mitral prostheses (St. Jude Medical, Inc., St. Jude, Minnesota) and in six patients who received Medtronic Hall mitral valves (Medtronic, Inc., Minneapolis, Minnesota). Maximal systolic regurgitant jet length and area determinations were obtained in all patients. A comparison of maximal jet lengths and areas for each type of mechanical prosthesis demonstrated that the Medtronic Hall prostheses produced longer maximal jet lengths (p = 0.0001) and larger jet areas (p = 0.0009) than those produced by the St. Jude Medical mitral valves. Medtronic Hall prostheses produce a large centrally directed jet, whereas St. Jude Medical prostheses typically generate three smaller jets. Recognition of these differences in transesophageal color flow Doppler images in these commonly used cardiac valve prostheses is necessary to avoid misinterpretation of the normally large systolic regurgitant jet of the Medtronic Hall prosthesis as representing prosthetic dysfunction.

Granulocyte interactions with GM-CSF and G-CSF secretion by endothelial cells and monocytes.

We have, in previous studies, characterized the cytokine and cellular regulation of GM-CSF and G-CSF production by monocytes and endothelial cells. In this study, we investigated the regulatory role of granulocytes. The addition of granulocytes to endotoxin-stimulated monocytes dose-dependently decreased both GM-CSF and G-CSF concentrations, presumably by absorbing the cytokines. A similar dose-dependent decrease in GM-CSF concentration was found when granulocytes were added to IL-1-stimulated endothelial cells. In contrast, G-CSF secretion by endothelial cells responded to granulocytes in a biphasic fashion. At low granulocyte concentrations, endothelial cells responded with an increased G-CSF secretion, but at high concentrations of granulocytes G-CSF secretion was down modulated. Our results suggest that there exist two loops between granulocytes and endothelial cells for regulating G-CSF activity. Granulocytes can stimulate G-CSF secretion by activated endothelial cells but can also decrease the biological activity by absorbing the cytokine. These mechanisms might be involved in the regulation of the local and systemic levels of granulocytes.

Health-related quality of life in multiple myeloma patients receiving high-dose chemotherapy with autologous blood stem-cell support.

In a population-based study, the Nordic Myeloma Study Group found a survival advantage for high-dose melphalan with autologous blood stem-cell support compared to conventional chemotherapy in myeloma patients under 60 yr of age (risk ratio: 1.62; confidence interval [CI] 1.22-2.15; p = 0.001). A study of health-related quality of life (HRQoL) was integrated in the trial, using the EORTC QLQ-C30 questionnaire. Of the 274 patients receiving intensive therapy 221 (81%) were compared to 113 (94%) of 120 patients receiving conventional melphalan-prednisone treatment. Prior to treatment, there were no statistically significant differences in any HRQoL score between the two groups. One month after the start of induction chemotherapy, the patients on intensive treatment had more sleep disturbance than the control patients. At 6 mo, corresponding to a mean of 52 d after high-dose melphalan, the patients on intensive treatment had moderately lower scores for global QoL and role and social functioning and there was also a significantly higher score for appetite loss. At 12 and 24 mo, the HRQoL was similar to that of the control patients. At 36 mo, there was a trend toward less fatigue, pain, nausea, and appetite loss in the intensive-treatment group. Thus, the 18 mo of prolonged survival seem to be associated with a good health-related quality of life. Despite the moderate HRQoL reduction associated with the early intensive chemotherapy phase, this treatment modality must be regarded as an important step forward in the care of multiple myeloma.

[High-dose melphalan with stem cell support is now an established myeloma therapy. Treatment of myeloma from a 30-year perspective]. / Högdos melfalan med stamcellsstöd nu etablerad terapi vid myelom. Myelombehandling i ett 30-årsperspektiv.

Melphalan and prednisone have been the backbone in myeloma therapy for more than 40 years. New developments in chemotherapy and supportive therapy, achieved during the two decades which preceded the use of high-dose chemotherapy with stem cell rescue, have not changed the overall prognosis. A study of high-dose melphalan with autologous stem cell support on 274 patients < 60 years, performed by the Nordic Myeloma Study Group, has shown a prolongation of the median survival by 1.5 years. The results confirm that this therapy is a major step forward in myeloma therapy. Cost-utility and quality-of-life studies show that high-dose therapy has acceptable costs and leads to a favorable long-term quality-of-life.

Potential adult sibling stem cell donors' perceptions and opinions regarding an information and care model.

The first international recommendations and guidelines for the care of sibling stem cell donors were established in 2010, and have not yet been evaluated. However, a model for information and care of adult potential sibling stem cell donors (the IC model) developed and introduced at the Skåne University Hospital, Lund, Sweden, in 2005 conforms closely to them. The IC model aims to protect the privacy of potential donors, support and respect their free choice, and identify quickly those unwilling or unable to donate and thus minimize delay in seeking alternative donors. To evaluate the IC model a questionnaire survey in 2010 gathered the perceptions and views on information provision; influences over decision making; and care provision under the IC model of 148 adult siblings informed about SCT donation, and asked to undergo HLA-typing since September 2005 at the hospital. The results suggest the IC model works well but highlights areas for improvement, such as in delivery of HLA typing results to non-matched siblings, and a need to further prevent complicating influence from health professionals and relatives on the decision to undergo HLA typing. Thus improved, the IC model could provide the groundwork for other SCT units seeking to implement the recommendations and guidelines.

The outcome of allo-HSCT for 92 patients with myelofibrosis in the Nordic countries.

Between 1982 and 2009 a total of 92 patients with myelofibrosis (MF) in chronic phase underwent allo-SCT in nine Nordic transplant centers. Myeloablative conditioning (MAC) was given to 40 patients, and reduced intensity conditioning (RIC) was used in 52 patients. The mean age in the two groups at transplantation was 46±12 and 55±8 years, respectively (P<0.001). When adjustment for age differences was made, the survival of the patients treated with RIC was significantly better (P=0.003). Among the RIC patients, the survival was significantly (P=0.003) better for the patients with age <60 years (a 10-year survival close to 80%) than for the older patients. The type of stem cell donor did not significantly affect the survival. No significant difference was found in TRM at 100 days between the MAC- and the RIC-treated patients. The probability of survival at 5 years was 49% for the MAC-treated patients and 59% in the RIC group (P=0.125). Patients treated with RIC experienced significantly less aGVHD compared with patients treated with MAC (P<0.001). The OS at 5 years was 70, 59 and 41% for patients with Lille score 0, 1 and 2, respectively (P=0.038, when age adjustment was made). Twenty-one percent of the patients in the RIC group were given donor lymphocyte infusion because of incomplete donor chimerism, compared with none of the MAC-treated patients (P<0.002). Nine percent of the patients needed a second transplant because of graft failure, progressive disease or transformation to AML, with no significant difference between the groups. Our conclusions are (1) allo-SCT performed with RIC gives a better survival compared with MAC. (2) age over 60 years is strongly related to a worse outcome and (3) patients with higher Lille score had a shorter survival.

Outcomes and prognostic factors of adults with acute lymphoblastic leukemia who relapse after allogeneic hematopoietic cell transplantation. An analysis on behalf of the Acute Leukemia Working Party of EBMT.

To describe outcomes, treatment and prognostic factors that influence survival of adult patients with acute lymphoblastic leukemia (ALL), who relapsed after allogeneic hematopoietic cell transplantation (HCT), we retrospectively analyzed 465 ALL adult patients from European Group for Blood and Marrow Transplantation (EBMT) centers who relapsed after a first HCT performed in complete remission (CR1 65%, CR2/3 35%). Salvage treatments were: supportive care (13%), cytoreductive therapy (43%), donor lymphocyte infusion without or with prior chemotherapy (23%) and second HCT (20%). Median time from HCT to relapse was 6.9 months, median follow-up was 46 months and median survival after relapse was 5.5 months. Estimated 1-, 2- and 5-year post-relapse survival was 30 ± 2%, 16 ± 2% and 8 ± 1%, respectively. In a multivariate analysis, adverse factors for survival were: late CR (CR2/3) at transplant (P<0.012), early relapse after transplant (<6.9 months, P <0.0001) and peripheral blast percent at relapse (P <0.0001). On the basis of multivariate model for survival, three groups of patients were identified with estimated 2 year survival of 6 ± 2, 17 ± 3 and 30 ± 7%. Outcome of ALL patients relapsing after HCT is dismal and there is a need for new therapies. Our study provides the standard expectations in ALL relapse and may help in the decision of post-relapse therapy.