Group For Marrow Transplantation Research Articles

Risk factors for outcomes after unrelated cord blood transplantation for adults with acute lymphoblastic leukemia: a report on behalf of Eurocord and the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

We performed a retrospective analysis on 421 adult patients who underwent unrelated cord blood transplantation (UCBT) for ALL. Median age was 32 years; 46% were in first CR (CR1), 32% in CR2 and 22% had advanced disease. Double UCBT was performed in 173 patients (41%). Myeloablative conditioning (MAC) was given to 314 patients (75%). Cumulative incidence (CI) of 60-day neutrophil recovery was 78%. CI of acute and chronic GVHD was 33 and 26%, respectively. Non-relapse mortality (NRM) at 2 years was 42%. Age⩾35 years (P<0.0001), advanced disease at UCBT (P<0.0001) and use of MAC (P<0.0001) were associated with increased NRM. Relapse incidence (RI) at 2 years was 28%; use of reduced intensity conditioning (RIC) (P=0.0002) was associated with increased RI. Two-year leukemia-free survival (LFS) was 39% for patients in CR1, 31% for CR2 and 8% for advanced disease. In multivariate analysis, factors associated with decreased LFS rate were: age ⩾35 years (P=0.034), use of MAC (P=0.032) and advanced disease (P<0.0001). These results show that UCBT is a valuable option to treat high-risk adult ALL when in remission. Strategies to decrease toxicity and relapse are needed to improve final outcomes.

Editorial introductions

Editorial introductions

Should the standard dimethyl sulfoxide concentration be reduced? Results of a European Group for Blood and Marrow Transplantation prospective noninterventional study on usage and side effects of dimethyl sulfoxide.

Dimethyl sulfoxide (DMSO) is essential for the preservation of liquid nitrogen-frozen stem cells, but is associated with toxicity in the transplant recipient. In this prospective noninterventional study, we describe the use of DMSO in 64 European Blood and Marrow Transplant Group centers undertaking autologous transplantation on patients with myeloma and lymphoma and analyze side effects after return of DMSO-preserved stem cells. While the majority of centers continue to use 10% DMSO, a significant proportion either use lower concentrations, mostly 5 or 7.5%, or wash cells before infusion (some for selected patients only). In contrast, the median dose of DMSO given (20 mL) was much less than the upper limit set by the same institutions (70 mL). In an accompanying statistical analysis of side effects noted after return of DMSO-preserved stem cells, we show that patients in the highest quartile receiving DMSO (mL and mL/kg body weight) had significantly more side effects attributed to DMSO, although this effect was not observed if DMSO was calculated as mL/min. Dividing the myeloma and lymphoma patients each into two equal groups by age we were able to confirm this result in all but young myeloma patients in whom an inversion of the odds ratio was seen, possibly related to the higher dose of melphalan received by young myeloma patients. We suggest better standardization of preservation method with reduced DMSO concentration and attention to the dose of DMSO received by patients could help reduce the toxicity and morbidity of the transplant procedure.

Oral squamous cell carcinoma positive for p16/human papilloma virus in post allogeneic stem cell transplantation: 2 cases and review of the literature

Complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) includes the risk of secondary malignancies. This may be related to mechanisms including radiation and chemotherapy regimens, chronic graft-versus-host disease, inflammation, and prolonged imunosuppression. Oral squamous cell carcinoma (OSCC) is a complication associated with chronic graft-versus-host disease after allo-HSCT. Although human papillomavirus (HPV) is known to be associated with OSCC, the role of HPV in development of OSCC in post-HSCT patients has not been studied. We identified 2 cases of OSCC in allo-HSCT recipients. Both biopsy specimens tested positive for p16(INK4A), a surrogate marker for HPV. We propose that the association of OSCC and HPV in patients after allo-HSCT may not be incidental. Clinical implications of these cases may imply the need for a HPV screening, early intervention, and consideration of anti-HPV vaccination in this population. The effectiveness of such interventions could be validated in a prospective clinical study.

Outcome of Allogeneic Stem Cell Transplantation for Patients Transformed to Myelodysplastic Syndrome or Leukemia from Severe Aplastic Anemia: A Report from the MDS Subcommittee of the Chronic Malignancies Working Party and the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation

One hundred and forty patients who had undergone hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) transformation after treatment of severe aplastic anemia (SAA) were identified in the European Group for Blood and Marrow Transplantation (EBMT) database. The median age at HSCT was 29 years (range, 1 to 66 years). The transplant donor was related in 49% cases and unrelated in 51% cases. The 5-year probability of relapse was 17%, and that of nonrelapse mortality was 41%. The 5-year overall survival was 45% ± 9%, better for patients untreated and patients in remission compared with patients with refractory disease. Our data indicate that allogeneic HSCT leads to prolonged survival in close to one-half of the patients transforming to MDS or AML from SAA.

THU0501 Hematopoietic Stem Cell Transplantation Increases Naive and Regulatory B Cells While Decreasing Memory B Cells in Systemic Sclerosis Patients

BackgroundHigh dose immunossuppression (HDI) followed by autologous hematopoietic stem cell transplantation (AHSCT) emerged in last past years as a therapeutic alternative for systemic sclerosis (SSc) patients [1]. The evaluation of...

Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation.

The use of a cytomegalovirus (CMV)-seronegative donor for a CMV-seronegative allogeneic hematopoietic stem cell transplant (HSCT) recipient is generally accepted. However, the importance of donor serostatus in CMV-seropositive patients is controversial. A total of 49 542 HSCT patients, 29 349 seropositive and 20 193 seronegative, were identified from the European Group for Blood and Marrow Transplantation database. Cox multivariate models were fitted to estimate the effect of donor CMV serological status on outcome. Seronegative patients receiving seropositive unrelated-donor grafts had decreased overall survival (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.06-1.21; P < .0001) compared with seronegative donors, whereas no difference was seen in patients receiving HLA-matched sibling grafts. Seropositive patients receiving grafts from seropositive unrelated donors had improved overall survival (HR, 0.92; 95% CI, .86-.98; P < .01) compared with seronegative donors, if they had received myeloablative conditioning. This effect was absent when they received reduced-intensity conditioning. No effect was seen in patients grafted from HLA-identical sibling donors. The same association was found if the study was limited to patients receiving transplants from the year 2000 onward. We confirm the negative impact on overall survival if a CMV-seropositive unrelated donor is selected for a CMV-seronegative patient. For a CMV-seropositive patient, our data support selecting a CMV-seropositive donor if the patient receives a myeloablative conditioning regimen.

Prediction of non-relapse mortality in recipients of reduced intensity conditioning allogeneic stem cell transplantation with AML in first complete remission.

Non-relapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (alloHSCT) can be predicted by the hematopoietic cell transplantation comorbidity index (HCT-CI) and the European Group for Blood and Marrow Transplantation (EBMT) score, which are composed of different parameters. We set out to integrate the parameters of both scores in patients with acute myeloid leukemia (AML) in first complete remission (CR1) receiving reduced intensity conditioning (RIC) alloHSCT. All parameters from the HCT-CI and the EBMT-score with the addition of patient and donor cytomegalovirus serology were evaluated in 812 patients by multivariable analysis with end-point NRM at 2 years. Subsequently, 16 parameters were selected based on hazard ratio >1.2, and were incorporated into a novel score, which was further internally validated by bootstrapping. Both the HCT-CI and the EBMT-score showed relatively weak predictive value, whereas the integrated score allowed to identify three clearly distinct risk groups with 2-year NRM estimates of 8±2% (low-risk), 17±2% (intermediate-risk) and 38±4% (high-risk), which also translated in prediction of overall survival. Collectively, integration of the most dominant parameters from the HCT-CI and the EBMT-score allowed to develop a simple and robust, integrated score with improved prediction of NRM for AML patients proceeding to RIC alloHSCT in CR1.

Intravenous busulfan for autologous stem cell transplantation in adult patients with acute myeloid leukemia: a survey of 952 patients on behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

Oral busulfan is the historical backbone of the busulfan+cyclophosphamide regimen for autologous stem cell transplantation. However intravenous busulfan has more predictable pharmacokinetics and less toxicity than oral busulfan; we, therefore, retrospectively analyzed data from 952 patients with acute myeloid leukemia who received intravenous busulfan for autologous stem cell transplantation. Most patients were male (n=531, 56%), and the median age at transplantation was 50.5 years. Two-year overall survival, leukemia-free survival, and relapse incidence were 67±2%, 53±2%, and 40±2%, respectively. The non-relapse mortality rate at 2 years was 7±1%. Five patients died from veno-occlusive disease. Overall leukemia-free survival and relapse incidence at 2 years did not differ significantly between the 815 patients transplanted in first complete remission (52±2% and 40±2%, respectively) and the 137 patients transplanted in second complete remission (58±5% and 35±5%, respectively). Cytogenetic risk classification and age were significant prognostic factors: the 2-year leukemia-free survival was 63±4% in patients with good risk cytogenetics, 52±3% in those with intermediate risk cytogenetics, and 37 ± 10% in those with poor risk cytogenetics (P=0.01); patients ≤50 years old had better overall survival (77±2% versus 56±3%; P<0.001), leukemia-free survival (61±3% versus 45±3%; P<0.001), relapse incidence (35±2% versus 45±3%; P<0.005), and non-relapse mortality (4±1% versus 10±2%; P<0.001) than older patients. The combination of intravenous busulfan and high-dose melphalan was associated with the best overall survival (75±4%). Our results suggest that the use of intravenous busulfan simplifies the autograft procedure and confirm the usefulness of autologous stem cell transplantation in acute myeloid leukemia. As in allogeneic transplantation, veno-occlusive disease is an uncommon complication after an autograft using intravenous busulfan.

Extreme heterogeneity of myeloablative total body irradiation techniques in clinical practice: a survey of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

Total body irradiation (TBI) is widely used for conditioning before hematopoietic cell transplantation. Its efficacy and toxicity may depend on many methodological aspects. The goal of the current study was to explore current clinical practice in this field. A questionnaire was sent to all centers collaborating in the European Group for Blood and Marrow Transplantation and included 19 questions regarding various aspects of TBI. A total of 56 centers from 23 countries responded. All centers differed with regard to at least 1 answer. The total maximum dose of TBI used for myeloablative transplantation ranged from 8 grays (Gy) to 14.4 Gy, whereas the dose per fraction was 1.65 Gy to 8 Gy. A total of 16 dose/fractionation modalities were identified. The dose rate ranged from 2.25 centigrays to 37.5 centigrays per minute. The treatment unit was linear accelerator (LINAC) (91%) or cobalt unit (9%). Beams (photons) used for LINAC were reported to range from 6 to 25 megavolts. The most frequent technique used for irradiation was "patient in 1 field," in which 2 fields and 2 patient positions per fraction are used (64%). In 41% of centers, patients were immobilized during TBI. Approximately 93% of centers used in vivo dosimetry with accepted discrepancies between the planned and measured doses of 1.5% to 10%. In 84% of centers, the lungs were shielded during irradiation. The maximum accepted dose for the lungs was 6 Gy to 14.4 Gy. TBI is an extremely heterogeneous treatment modality. The findings of the current study should warrant caution in the interpretation of clinical studies involving TBI. Further investigation is needed to evaluate how methodological differences influence outcome. Efforts to standardize the method should be considered.

EBMT risk score can predict the outcome of leukaemia after unmanipulated haploidentical blood and marrow transplantation.

Systematic, standardised pretransplant risk assessment is an important tool for predicting patient outcomes following allogeneic haematopoietic SCT (HSCT). To assess the European Group for Blood and Marrow Transplantation (EBMT) risk score capacities for predicting patient outcomes following unmanipulated haploidentical blood and marrow transplantation (HBMT), we analysed 502 leukaemia patients who received transplants at our centre between 2008 and 2010. The cohort OS and leukaemia-free survival (LFS) were 72.1% and 68.1%, whereas the cumulative non-relapse mortality (NRM) and relapse incidences were 16.5% and 16.1%. According to univariate analysis, the values for OS, LFS and NRM were worse for an EBMT risk score of 6 (40.0, 40.0, 50.0%) than a score of 1 (83.1, 78.3, 8.4%). Hazard ratios steadily increased for each additional score point. Likewise, a higher EBMT risk score was associated with an increased relapse incidence. Importantly, the EBMT risk score prognostic value regarding OS, LFS, NRM and relapse was maintained in the multivariate analysis. Moreover, we also made a haploidentical EBMT (haplo-EBMT) risk score, which used number of HLA disparity instead of donor type, and the haplo-EBMT risk scores can also be used to predict patient outcomes following unmanipulated HBMT.

The role of allogeneic stem cell transplantation in Hodgkin's lymphoma.

The treatment of patients with classical Hodgkin's lymphoma relapsing after autologous stem cell transplantation represents a clear unmet need. Overall long-term outcome is not the same in these patients and therapeutic options in this setting are very heterogeneous and include salvage CT and/or RT followed or not by a second stem cell transplantation, palliative care, new drugs, or biological agents. Despite the absence of prospective, randomized, clinical trials, allogeneic stem cell transplantation either from a HLA identical sibling or a matched, unrelated donor represents an attractive option for those young patients with chemosensitive disease after being treated with a salvage protocol. The use of reduced intensity conditioning regimens has been able to drastically decrease nonrelapse mortality, although relapse rate remains a significant issue in this setting. More intense conditioning protocols could eventually decrease the relapse rate after the allogeneic procedure and, as indicated by a recent retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation, nonrelapse mortality does not represent a major problem nowadays for patients with multiply relapsed Hodgkin's lymphoma. Brentuximab vedotin is an antibody-drug conjugate that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. Its use has been approved recently for patients with Hodgkin's lymphoma relapsing after autologous stem cell transplantation. As a single dose, brentuximab vedotin is able to achieve an objective response rate of 75% with 34% of the patients achieving a complete remission. Its widespread use will most certainly change the treatment paradigm of this subgroup of patients, either avoiding the allogeneic procedure in some patients or by increasing the group of potential candidates to an allogeneic transplant being used as a "bridge to allo." Additional information on long-term outcome of patients being treated with this drug or the development of prospective clinical trials in this setting will most probably give some light to this question we have nowadays.

Microbial monitoring and methods of sample collection: a GITMO survey (Gruppo Trapianto di Midollo Osseo).

The collection of microbiological samples represents an important aspect of care both for doctors as well as nurses. It is important to recognise and identify some key points, to avoid performing ‘unnecessary’ or ‘incorrect’ sampling, which may give useless or even misleading results, these are: the moment at which the sample is collected, the collection method and timing (if indicated). The comparison between the various nursing members of the Italian National bone marrow transplant group (GITMO), showed diversity of practice across all fields. A formal survey was therefore conducted within GITMO centres looking at the methods of microbiological sample collection. These results were compared with the literature, and in addition to the lack of homogeneity of practice within the centres, a lack of compliance with the recommendations was also observed. To evaluate the effectiveness of this survey in highlighting awareness of this issue and the presence of relevant guidelines, the questionnaire was repeated (with the same centres responding), which demonstrated no major changes in care practices.Conclusion:The survey has allowed us to highlight many critical issues regarding common procedures which are not commonly discussed. Considerable differences were noted between different transplant centres, which may be attributable to the lack of Italian guidelines that can be used as a starting point for clinical practice. The plenary discussion allowed for an exchange of findings with the medical staff, who are usually responsible for requesting microbiological samples. The ideal solution would be a unique field-based training programme, associated with the dissemination of a common procedural document for ensuring evidence-based practice.

Autologous haematopoietic stem cell mobilisation in multiple myeloma and lymphoma patients: a position statement from the European Group for Blood and Marrow Transplantation

Autologous haematopoietic SCT with PBSCs is regularly used to restore BM function in patients with multiple myeloma or lymphoma after myeloablative chemotherapy. Twenty-eight experts from the European Group for Blood and Marrow Transplantation developed a position statement on the best approaches to mobilising PBSCs and on possibilities of optimising graft yields in patients who mobilise poorly. Choosing the appropriate mobilisation regimen, based on patients' disease stage and condition, and optimising the apheresis protocol can improve mobilisation outcomes. Several factors may influence mobilisation outcomes, including older age, a more advanced disease stage, the type of prior chemotherapy (e.g., fludarabine or melphalan), prior irradiationor a higher number of prior treatment lines. The most robust predictive factor for poor PBSC collection is the CD34(+) cell count in PB before apheresis. Determination of the CD34(+) cell count in PB before apheresis helps to identify patients at risk of poor PBSC collection and allows pre-emptive intervention to rescue mobilisation in these patients. Such a proactive approach might help to overcome deficiencies in stem cell mobilisation and offers a rationale for the use of novel mobilisation agents.

Validation of the European Group for Blood and Marrow Transplantation (EBMT) risk score in patients receiving allogeneic hematopoietic stem cell transplantation at a single center in Japan

We validated the European Group for Blood and Marrow Transplantation (EBMT) risk score in 273 consecutive adult patients receiving allogeneic hematopoietic stem cell transplantation between 2000 and 2010 at our center. The patients were divided into four groups according to the EBMT risk score: low risk (LR, score 0-2), intermediate risk-1 (IR-1, score 3), intermediate risk-2 (IR-2, score 4), and high risk (HR, score 5-7). The five-yr overall survival of the LR (n=65), IR-1 (n=67), IR-2 (n=70), and HR (n=71) groups was 72%, 57%, 41%, and 25%, respectively (p<0.001). The five-yr transplant-related mortality rates were 16%, 30%, 25%, and 36%, respectively (p=0.07). The five-yr cumulative incidence of relapse was 20%, 18%, 37%, and 41%, respectively (p<0.001). In the subgroup analysis, the prognostic value of the EBMT risk score was confirmed in patients undergoing myeloablative conditioning (MAC), but not in those undergoing reduced-intensity conditioning (RIC). The results suggest that the EBMT risk score is a useful tool to predict transplant outcome for patients undergoing MAC, but not for those undergoing RIC and may be beneficial for stratifying patients in clinical studies.

Outcome and prognostic factors in patients with mantle-cell lymphoma relapsing after autologous stem-cell transplantation: a retrospective study of the European Group for Blood and Marrow Transplantation (EBMT)

Autologous stem-cell transplantation (autoSCT) is considered a standard treatment of non-frail patients with mantle cell lymphoma (MCL), but little is known about outcome of MCL patients relapsing after autoSCT. We therefore sought to analyse the outcome after autoSCT failure and the efficacy of a rescue stem-cell transplantation (SCT) in this setting. Patients with MCL were eligible if they had relapsed after autoSCT performed between 2000 and 2009. A total of 1054 patients could be identified in the EBMT registry. By contacting the transplant centres, a full dataset could be retrieved for 360 patients. Median overall survival (OS) after relapse of the whole study group was 19 months. A long (>12 months) interval between autoSCT and relapse [P < 0.001, hazard ratio (HR) 0.62], primary refractory disease (P < 0.02, HR 1.92), prior high-dose ARA-C treatment (P = 0.04, HR 1.43), and the year of relapse (P = 0.02, HR 0.92) significantly influenced OS from relapse in multivariate analysis. Eighty patients (22%) received a rescue allogeneic SCT (alloSCT). Relapse incidence, non-relapse mortality, and OS 2 years after alloSCT was 33% [confidence interval (95% CI 21% to 45%)], 30% (95% CI 19% to 42%), and 46% (95% CI 33% to 59%), respectively. Remission duration after autoSCT was the only variable significantly affecting the outcome of salvage alloSCT. In contrast, rescue autoSCT was not associated with long-term disease control. However, individual patients survived long term even without salvage transplantation. MCL recurrence within 1 year after autoSCT has an extremely dismal outcome, while the prognosis of patients with longer remission durations after autoSCT is significantly better. AlloSCT may offer the possibility of durable survival when performed for patients with a remission duration of more than 12 months after first autoSCT, but the favourable effect of a salvage alloSCT in this setting needs further validation.

Matched unrelated donor allogeneic transplantation provides comparable long-term outcome to HLA-identical sibling transplantation in relapsed diffuse large B-cell lymphoma

The objective of this retrospective analysis was to compare outcomes of patients with diffuse large B-cell lymphoma (DLBCL) who received either a matched sibling (sib) or an unrelated donor (URD) allogeneic hematopoietic cell transplantation (allo-HCT). Long-term outcome of 172 DLBCL patients receiving URD-HCT between 2000 and 2007 and reported to the European Group for Blood and Marrow Transplantation, was compared with that of 301 subjects, allografted from sib-HCT. With a median follow-up of 45 months, 3-year PFS approached 35% for both groups; overall survival (OS) was 42% for sib-HCT versus 37% for URD (NS). Multivariate analyses confirmed that donor type was not associated with differences in non-relapse mortality (NRM), relapse rate (RR), PFS or OS. Poor performance status (PS) and refractory disease adversely affected PFS and OS. Prior auto-SCT and multiple previous therapies predicted for shorter PFS. NRM was adversely affected by older age (⩾50 years), poor PS and refractory disease, and RR by time from diagnosis to allo-HCT of <36 months, prior auto-SCT, refractory disease, poor PS and in vivo T-cell depletion with alemtuzumab. This large study shows for the first time that URD-HCT is not inferior to sib-HCT, providing a reasonable therapeutic approach for DLBCL patients, having no HLA-identical sibling available.

Impact of in vivo T-cell depletion on outcome of AML patients in first CR given peripheral blood stem cells and reduced-intensity conditioning allo-SCT from a HLA-identical sibling donor: a report from the Acute Leukemia Working Party of the European group for Blood and Marrow Transplantation

The impact of in vivo T-cell depletion on transplantation outcomes in patients transplanted with reduced-intensity conditioning (RIC) remains controversial. This study assessed the outcome of 1250 adult patients with de novo AML in first CR (CR1) given PBSC from HLA-identical siblings after chemotherapy-based RIC. A total of 554 patients did not receive any form of in vivo T-cell depletion (control group), whereas antithymocyte globulin (ATG) and alemtuzumab were given in 444 and 252 patients, respectively. The incidences of grade II-IV acute GVHD were 21.4, 17.6 and 10.2% in control, ATG and alemtuzumab patients, respectively (P<0.001). In multivariate analysis, the use of ATG and the use of alemtuzumab were each associated with a lower risk of chronic GVHD (P<0.001 each), but a similar risk of relapse, and of nonrelapse mortality, and similar leukemia-free survival and OS. Further, among patients given BU-based RIC, the use of <6 mg/kg ATG did not increase the risk of relapse (hazard ratio, HR=1.1), whereas there was a suggestion for higher relapse risk in patients given 6 mg/kg ATG (HR=1.4, P=0.08). In summary, these data suggest that a certain amount of in vivo T-cell depletion can be safely used in the conditioning of AML patients in CR1 given PBSC after chemotherapy-based RIC.

Nurses' practice patterns in relation to adherence-enhancing interventions in stem cell transplant care: a survey from the Nurses Group of the European Group for Blood and Marrow Transplantation

Recipients of stem cell transplants (SCT) must accurately manage multiple medications as non-adherence jeopardises treatment benefits. There is an evidence base for the efficacy of adherence-enhancing interventions; however, level of clinical implementation is unknown. This study aimed to identify patterns of practice in assessing medication adherence, screening for risk factors of non-adherence, interventions used in SCT to improve adherence and how nurses perceive the effectiveness of such interventions. A convenience sample of 143 European nurses completed a 29-item questionnaire measuring the frequency and perceived effectiveness of assessment/screening methods for adherence and three types of intervention (educational/cognitive, counselling/behavioural and psychological/affective). Questioning patients about adherence was the most regularly used assessment method (51.5%). Nurses used a median of seven interventions (interquartile range: six) 'frequently', the most popular being provision of reading materials (79%). The interventions perceived as most effective were; providing individual patient/family with teaching and reading materials. This is the first study exploring patterns of practice relating to adherence in SCT. Educational interventions were the most frequently employed style of intervention, which is at odds with recent data suggesting limited efficacy with this style of intervention. Combining educational, behavioural and psychological interventions would more accurately embrace current understanding.

Allogeneic hematopoietic stem cell transplantation in patients with polycythemia vera or essential thrombocythemia transformed to myelofibrosis or acute myeloid leukemia: a report from the MPN Subcommittee of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation

The clinical course of polycythemia vera and essential thrombocythemia is potentially associated with long-term severe complications, such as evolution to myelofibrosis or acute myeloid leukemia. Allogeneic stem cell transplantation is currently the only potentially curative treatment for advanced polycythemia vera or essential thrombocythemia. We analyzed 250 consecutive patients with an initial diagnosis of polycythemia vera (n=120) or essential thrombocythemia (n=130), who underwent transplantation due to progression to myelofibrosis (n=193) or acute myeloid leukemia (n=57) and who were reported to the European Group for Blood and Marrow Transplantation registry between 1994 and 2010. Their median age was 56 years (range, 22-75) and in 52% of cases the interval between diagnosis and transplantation was 10 years or more. With a median follow-up from transplantation of 13 months, the 3-year overall survival rate and relapse incidence were 55% and 32%, respectively. In univariate analysis, the main parameters that negatively affected post-transplantation outcomes were older age (>55 years), a diagnosis at transplant of acute myeloid leukemia and the use of an unrelated donor. The overall 3-year cumulative incidence of non-relapse mortality was 28%, but was significantly higher in older patients than in younger ones (>55 years, 35% versus 20%, P=0.032), in those transplanted from an unrelated donor rather than a related donor (34% versus 18%, P=0.034) and in patients with a diagnosis of acute myeloid leukemia compared to myelofibrosis (29% versus 27%, P=0.045). This large retrospective study confirms that transplantation is potentially curative for patients with end-stage polycythemia vera/essential thrombocythemia progressing to myelofibrosis or acute myeloid leukemia. Relapse and non-relapse mortality remain unsolved problems for which innovative treatment approaches need to be assessed.