Controlled donation after circulatory death lung transplantation: Results of the French protocol including in situ abdominal normothermic regional perfusion and ex vivo lung perfusion.

BACKGROUND: The French national protocol for controlled donation after circulatory determination of death (cDCD) includes normothermic regional perfusion (NRP) in case of abdominal organ procurement and additional ex-vivo lung perfusion (EVLP) before considering lung transplantation (LT). METHODS: We made a retrospective study of a prospective registry that included all donors considered for cDCD LT from the beginning of the program in May 2016 to November 2021. RESULTS: One hundred grafts from 14 donor hospitals were accepted by 6 LT centers. The median duration of the agonal phase was 20 minutes [2-166]. The median duration from circulatory arrest to pulmonary flush was 62 minutes [20-90]. Ten lung grafts were not retrieved due to prolonged agonal phases (n = 3), failure of NRP insertion (n = 5), or poor in situ evaluation (n = 2). The remaining 90 lung grafts were all evaluated on EVLP, with a conversion rate of 84% and a cDCD transplantation rate of 76%. The median total preservation time was 707 minutes [543-1038]. Seventy-one bilateral LTs and 5 single LTs were performed for chronic obstructive pulmonary disease (n = 29), pulmonary fibrosis (n = 21), cystic fibrosis (n = 15), pulmonary hypertension (n = 8), graft-versus-host disease (n = 2), and adenosquamous carcinoma (n = 1). The rate of PGD3 was 9% (n = 5). The 1-year survival rate was 93.4%. CONCLUSION: After initial acceptance, cDCD lung grafts led to LT in 76% of cases, with outcomes similar to those already reported in the literature. The relative impacts of NRP and EVLP on the outcome following cDCD LT should be assessed prospectively in the context of comparative studies.

[What place for lung volume reduction surgery for emphysema?] / Quelle place pour la réduction de volume pulmonaire chirurgicale dans l'emphysème ?

Lung volume reduction surgery (LVRS) has been part of the management for the treatment of selected emphysematous patients for two decades. In a large randomized American trial (NETT), lung volume reduction surgery was shown to improve overall survival at 5 years as well as exercise capacity and health-related quality of life, especially in cases of upper-lobe-predominant emphysema and low exercise capacity. Inclusion criteria were pretreatment FEV1≤45 %, TLC≥100 %, RV≥150 %, room air resting PaCO2≤60mmHg and PaO2≥45mmHg. Patients with FEV1≤20 % and either a DLCO<20 % or homogeneous emphysema were at increased risk of mortality following LVRS and should not be considered for this procedure. Despite this evidence base, lung volume reduction surgery is performed infrequently, competing with lung transplantation and new endoscopic volume reduction techniques.

Clinical significance of Koebner phenomenon in vitiligo.

BACKGROUND: The clinical significance of Koebner phenomenon (KP) in vitiligo with respect to disease activity and course is still debatable. Recently, a new classification was introduced for the assessment of KP. OBJECTIVES: To evaluate the new assessment method for KP in clinical practice and to determine its clinical significance, both with respect to the clinical profile, course of vitiligo and treatment response. METHODS: Seven hundred patients with generalized vitiligo were included in this observational cohort study. KP was classified according to the new classification system into different subtypes [KP1, by history; KP2A and KP2B, by clinical examination (A, lesions on friction areas; B, linear, artefactual lesions)]. RESULTS: KP1 was positive in 34·1% of the patients, 66·3% were KP2A positive and 15·1% showed KP2B. The body surface area (BSA) was significantly (P < 0·001) higher in the presence of any KP subtype and more disease activity was found in KP1-positive and KP2B-positive patients. An earlier age at onset and elevated risk of further depigmentation despite treatment were observed in all KP-positive groups. In KP2A- and KP2B-positive patients, depigmentation of wrists/ankles was more common. In the KP2A-positive group, a significantly higher prevalence of thyroid disease was found while autoimmune diseases were less prevalent in KP2B-positive patients. CONCLUSION: The new assessment method for KP, taking into account both history and clinical examination, seems to be a useful and valuable tool for assessing KP in daily practice. Our results support the hypothesis that KP may function as a clinical parameter to assess and predict the clinical profile and course of vitiligo.

Transfused stored platelets have the same haemostatic function as circulating native platelets.

BACKGROUND AND OBJECTIVES: As thrombelastography (TEG) measures haemostasis in whole blood, we used this instrument to study whether transfused platelets (PLTs) have the same haemostatic function compared to native circulating PLTs. Further, we studied the effect of storage time on the haemostatic potential of platelet concentrates (PCs). MATERIALS AND METHODS: During the decrease in PLT count after chemotherapy, TEG parameters were measured serially until the transfusion trigger was reached in 92 patients. TEG parameters for different ranges of native circulating PLTs could be assessed, which were compared to ranges obtained in the thrombocytopenic period in which the patient received PLT transfusions. Finally, we compared the haemostatic potential of fresh PCs (1-3 days) with PCs with longer storage time (4-5 days). RESULTS: No differences could be found in haemostatic potential between native PLTs and transfused stored PLTs (all P-values > or = 0.1). The transfusion of fresh PLTs demonstrated better haemostatic effects than longer stored PLTs, measured 1 h after transfusion. Both the time until a fixed level of clot firmness was reached (K-time) and the rate of clot growth (alpha angle) were superior for fresh PCs. CONCLUSION: TEG is able to monitor the haemostatic effects of PLT transfusion, with comparable haemostatic properties of native circulating and transfused stored-PLTs. Further, our data suggest that limited storage time is associated with a better haemostatic capacity. However, before TEG can be applied as a qualitative test in PLT transfusion, further research is needed with focus on clinical outcomes like bleeding episodes.

Erythroid precursors from patients with low-risk myelodysplasia demonstrate ultrastructural features of enhanced autophagy of mitochondria.

Recent studies in erythroid cells have shown that autophagy is an important process for the physiological clearance of mitochondria during terminal differentiation. However, autophagy also plays an important role in removing damaged and dysfunctional mitochondria. Defective mitochondria and impaired erythroid maturation are important characteristics of low-risk myelodysplasia. In this study we therefore questioned whether the autophagic clearance of mitochondria might be altered in erythroblasts from patients with refractory anemia (RA, n=3) and RA with ringed sideroblasts (RARS, n=6). Ultrastructurally, abnormal and iron-laden mitochondria were abundant, especially in RARS patients. A large proportion (52+/-16%) of immature and mature myelodysplastic syndrome (MDS) erythroblasts contained cytoplasmic vacuoles, partly double membraned and positive for lysosomal marker LAMP-2 and mitochondrial markers, findings compatible with autophagic removal of dysfunctional mitochondria. In healthy controls only mature erythroblasts comprised these vacuoles (12+/-3%). These findings were confirmed morphometrically showing an increased vacuolar surface in MDS erythroblasts compared to controls (P<0.0001). In summary, these data indicate that MDS erythroblasts show features of enhanced autophagy at an earlier stage of erythroid differentiation than in normal controls. The enhanced autophagy might be a cell protective mechanism to remove defective iron-laden mitochondria.

Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial.

BACKGROUND: Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. We assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP. METHODS: In two parallel trials, 63 splenectomised and 62 non-splenectomised patients with ITP and a mean of three platelet counts 30x10(9)/L or less were randomly assigned 2:1 to subcutaneous injections of romiplostim (n=42 in splenectomised study and n=41 in non-splenectomised study) or placebo (n=21 in both studies) every week for 24 weeks. Doses of study drug were adjusted to maintain platelet counts of 50x10(9)/L to 200x10(9)/L. The primary objectives were to assess the efficacy of romiplostim as measured by a durable platelet response (platelet count > or =50x10(9)/L during 6 or more of the last 8 weeks of treatment) and treatment safety. Analysis was per protocol. These studies are registered with ClinicalTrials.gov, numbers NCT00102323 and NCT00102336. FINDINGS: A durable platelet response was achieved by 16 of 42 splenectomised patients given romplostim versus none of 21 given placebo (difference in proportion of patients responding 38% [95% CI 23.4-52.8], p=0.0013), and by 25 of 41 non-splenectomised patients given romplostim versus one of 21 given placebo (56% [38.7-73.7], p<0.0001). The overall platelet response rate (either durable or transient platelet response) was noted in 88% (36/41) of non-splenectomised and 79% (33/42) of splenectomised patients given romiplostim compared with 14% (three of 21) of non-splenectomised and no splenectomised patients given placebo (p<0.0001). Patients given romiplostim achieved platelet counts of 50x10(9)/L or more on a mean of 13.8 (SE 0.9) weeks (mean 12.3 [1.2] weeks in splenectomised group vs 15.2 [1.2] weeks in non-splenectomised group) compared with 0.8 (0.4) weeks for those given placebo (0.2 [0.1] weeks vs 1.3 [0.8] weeks). 87% (20/23) of patients given romiplostim (12/12 splenectomised and eight of 11 non-splenectomised patients) reduced or discontinued concurrent therapy compared with 38% (six of 16) of those given placebo (one of six splenectomised and five of ten non-splenectomised patients). Adverse events were much the same in patients given romiplostim and placebo. No antibodies against romiplostim or thrombopoietin were detected. INTERPRETATION: Romiplostim was well tolerated, and increased and maintained platelet counts in splenectomised and non-splenectomised patients with ITP. Many patients were able to reduce or discontinue other ITP medications. Stimulation of platelet production by romiplostim may provide a new therapeutic option for patients with ITP.

Megakaryocytic dysfunction in myelodysplastic syndromes and idiopathic thrombocytopenic purpura is in part due to different forms of cell death.

Platelet production requires compartmentalized caspase activation within megakaryocytes. This eventually results in platelet release in conjunction with apoptosis of the remaining megakaryocyte. Recent studies have indicated that in low-risk myelodysplastic syndromes (MDS) and idiopathic thrombocytopenic purpura (ITP), premature cell death of megakaryocytes may contribute to thrombocytopenia. Different cell death patterns have been identified in megakaryocytes in these disorders. Growing evidence suggests that, besides apoptosis, necrosis and autophagic cell death, may also be programmed. Therefore, programmed cell death (PCD) can be classified in apoptosis, a caspase-dependent process, apoptosis-like, autophagic and necrosis-like PCD, which are predominantly caspase-independent processes. In MDS, megakaryocytes show features of necrosis-like PCD, whereas ITP megakaryocytes demonstrate predominantly characteristics of apoptosis-like PCD (para-apoptosis). Triggers for these death pathways are largely unknown. In MDS, the interaction of Fas/Fas-ligand might be of importance, whereas in ITP antiplatelet autoantibodies recognizing common antigens on megakaryocytes and platelets might be involved. These findings illustrate that cellular death pathways in megakaryocytes are recruited in both physiological and pathological settings, and that different forms of cell death can occur in the same cell depending on the stimulus and the cellular context. Elucidation of the underlying mechanisms might lead to novel therapeutic interventions.

Cost-effectiveness of pathogen inactivation for platelet transfusions in the Netherlands.

The objective of this study is to estimate cost-effectiveness of pathogen inactivation for platelet transfusions in the Netherlands. We used decision tree analysis to evaluate the cost-effectiveness of the addition of pathogen inactivation of pooled platelets to standard procedures for platelet transfusion safety (such as, donor recruitment and screening). Data on transfusions were derived from the University Medical Centre Groningen (the Netherlands) for 1997. Characteristics of platelet recipients (patient group, age, gender and survival) and data/assumptions on viral and bacterial risks were linked to direct and indirect costs/benefits of pathogen inactivation. Post-transfusion survival was simulated with a Markov model. Standard methods for cost-effectiveness were used. Cost-effectiveness was expressed in net costs per life-year gained (LYG) and estimated in baseline- and sensitivity analysis. Sensitivity was analysed with respect to various assumptions including sepsis risk, reduction of the discard rate and discounting. Stochastic analysis to derive 90% simulation intervals (SIs) was performed on sepsis risk. Net costs per LYG for pathogen inactivation were estimated 554,000 euro in the baseline-weighted average over the three patient groups (90% SI: 354,000-1092,500 euro). Sensitivity analysis revealed that cost-effectiveness was insensitive to viral risks and indirect costing, but highly sensitive to the assumed excess transfusions required and discounting of LYG. Given relatively high net costs per LYG that are internationally accepted for blood transfusion safety interventions, our estimated cost-effectiveness figures for pathogen inactivation may reflect acceptable cost-effectiveness in this specific area. Two main assumptions of our model were that the pathogen inactivation was 100% effective in preventing transmission of the pathogens considered and was not associated with major and/or costly adverse reactions. Validation of several crucial parameters is required, in particular the Dutch risk for acquiring and dying of transfusion-related sepsis.

Splenectomy for the treatment of thrombotic thrombocytopenic purpura.

Plasma exchange is the treatment of choice for patients with thrombotic thrombocytopenic purpura (TTP) and results in remission in >80% of the cases. Treatment of patients who are refractory to plasma therapy or have relapsing disease is difficult. Splenectomy has been a therapeutic option in these conditions but its value remains controversial. We report on a series of 33 patients with TTP who were splenectomised because they were plasma refractory (n = 9) or for relapsed disease (n = 24). Splenectomy generated prompt and unmaintained remissions in all except five patients, in whom remission was delayed (n = 4) or who died with progressive disease (n = 1). Four postoperative complications occurred: one pulmonary embolism and three surgical complications. Median follow-up after splenectomy was 109 months (range 28-230 months). The overall postsplenectomy relapse rate was 0.09 relapses/patient-year and the 10-year relapse-free survival (RFS) was 70% (95% CI 50-83%). In the patients with relapsing TTP, relapse rate fell from 0.74 relapses/patient-year before splenectomy to 0.10 after splenectomy (P < 0.00001). Two patients died from first postsplenectomy relapse. Although these results are based on retrospective data and that the relapse rate may spontaneously decrease with time, we conclude that splenectomy, when performed during stable disease, has an acceptable safety profile and should be considered in cases of plasma refractoriness or relapsing TTP to reach durable remissions and to reduce or prevent future relapses.

Intraoperative blood transfusion requirement is the main determinant of early surgical re-intervention after orthotopic liver transplantation.

Liver transplantation is the treatment of choice in selected patients with end-stage liver disease. Postoperative complications often require surgical re-intervention. This study is a retrospective single-centre study to assess the incidence and type of surgical re-intervention during the in-hospital period after liver transplantation and to identify predictors of this re-intervention. From 1994 to 2002, 231 consecutive adult liver transplantations were performed. Re-intervention was classified as biliary, vascular, bleeding, septicaemia, re-transplantation or as miscellaneous. One hundred and thirty-nine surgical re-interventions were performed in 79 of 231 patients (34%). Septicaemia (44%) and bleeding (27%) were the most frequent indications for re-intervention, followed by biliary (10%) re-intervention. Vascular re-intervention, re-transplantation, and re-intervention for miscellaneous reasons, were performed in 7% each. Of all analysed variables (gender, age, diagnosis, acute liver failure, Child-Pugh classification, Karnofsky score, previous abdominal surgery, creatinine clearance, prothrombin time, anti-thrombin, platelet count, surgical technique, cold ischaemia time, warm ischaemia time, functional anhepatic time, anatomic anhepatic time, revascularisation time, year of transplantation, aprotinin administration, transfused platelet concentrate, and red blood cell transfusion requirements), only the number of transfused red blood cell concentrates (RBCs) was identified as a predictor of surgical re-intervention. Median RBC transfusion requirement during liver transplantation was 2.9 l (range 0-18.8 l) in the re-intervention group compared with 1.5 l (range 0-13.4 l) in the non-re-intervention group (P<0.001). This study revealed intraoperative blood loss as the main determinant of early surgical re-intervention after liver transplantation and emphasises the need for further attempts to control blood loss during liver transplantation.

Adjusted transfusion triggers improve transfusion practice in orthopaedic surgery.

Although blood transfusion has never been safer, there remains concern about adverse effects. We designed guidelines, the 6-8-10-Flexinorm, based on the conditions which are relevant to the decision to transfuse. To evaluate these new guidelines, we performed a case-control study in patients undergoing elective primary total hip replacement. The study consisted of two parts. In the first part, physicians were strongly encouraged to use the new guidelines; in the second part, only registration took place. During the first and second part of the study, the use of packed red cells (PRC) in Hospital A (study hospital) decreased from 1.1 +/- 1.5 to 0.6 +/- 1.2 and 0.3 +/- 0.9 units, whereas in Hospital B (control), the use of PRC remained unchanged (1 +/- 1.5, 1 +/- 1.7 and 1 +/- 2 units). In the prestudy groups, 43% of the patients in Hospital A were transfused compared to 45% in Hospital B. In the first and second part of the study, 27%, respectively, 14% of the patients in Hospital A were transfused compared to 40% in both periods in Hospital B. The new guidelines lead to a reduction in the use of allogeneic blood and a decrease in the number of patients transfused.

Limited numbers of apoptotic cells in fresh paraffin embedded bone marrow samples of patients with myelodysplastic syndrome.

In myelodysplasia (MDS) the precise mechanism of ineffective erythropoiesis is not fully elucidated, but it is suggested that apoptosis may contribute to this process. We performed TdT-mediated dUTP-nick end labelling (TUNEL) staining of paraffin embedded bone marrow specimens to assess the amount of apoptotic cells in 21 MDS patients (7 RA, 3 RARS, 5 RAEB, 3 RAEB-T, 3 CMML) and five normal controls. In 10 MDS patients the TUNEL assay was performed in combination with immunostaining for Glycophorin-A (GpA) to determine apoptosis in the maturing erythroid compartment. To assess the proliferation of the bone marrow cells the expression of Ki-67 antigen was used as a marker. The mean apoptotic index (AI) in MDS patients was not increased (2.3 +/- 3.0% in MDS versus 4.8 +/- 1.2% in normal controls (P < 0.05)). Moreover, no significant difference in mean AI was observed in the GpA+ compartment between MDS and normal controls (0.8 +/- 0.2% versus 0.6 +/- 0.1%). In addition the different FAB-classifications and the different International Prognostic Scoring System (IPSS)-risk groups showed no significant differences between the subgroups. The expression of Ki-67, as marker for proliferative activity, in the GpA+ compartment from MDS did not differ significantly from normal controls (84.0 +/- 12.2% versus 79.9 +/- 20.2%). Our findings suggest that the observed increased apoptosis in in vitro culture assays is related to the detachment of the cells from the microenvironment leading to an increased susceptibility to apoptosis.

Factors influencing haematological recovery following high-dose chemotherapy and peripheral stem-cell transplantation for haematological malignancies; 1-year analysis.

Peripheral blood counts and factors influencing haematological recovery in 98 patients with a relapse-free survival of > or =1 year treated with high-dose chemotherapy (HDC) and peripheral stem-cell transplantation (PSCT) for haematological malignancies were analysed. One year after PSCT full haematological recovery was demonstrated for haemoglobin (Hb) in 47% of patients, for the white blood cell count (WBC) in 94%, and for platelets in 64%; 39% had a trilineage recovery. In the multivariate analysis, recovery was influenced by age (P=0.002), number of reinfused CD34+ cells (P=0.016), Hb at start of HDC (P=0.001), and platelets at start of HDC (P=0.008). One year following PSCT, 61% of patients still have subnormal values in one or more haematopoietic cell lineage, suggesting a limited bone-marrow reserve. Long-term recovery is highly dependent on age, blood counts at start of HDC and number of reinfused CD34+ cells without a threshold, all reflecting the residual function of bone marrow before HDC. Reinfusing more CD34+ cells can accelerate long-term haematological recovery.

Phosphorescence-Fluorescence ratio imaging for monitoring the oxygen status during photodynamic therapy.

The effectiveness of photodynamic therapy is strongly dependent on the availabilty of oxygen. In the present paper we show that the ratio between photosensitiser phosphorescence and fluorescence is a parameter that can be used to monitor the competition between singlet oxygen production and other processes quenching the photosensitiser triplet state. We present a theoretical basis for the validity of this approach and a series of in vitro imaging experiments.

Pharmaco-economics of blood transfusion safety: review of the available evidence.

BACKGROUND AND OBJECTIVES: Pharmaco-economics provides a standardized methodology for valid comparisons of interventions in different fields of health care. The role of pharmaco-economics in the safety of blood and blood products has, however, been very limited to date. This review discusses the pharmaco-economic evaluations of strategies to enhance blood product safety that have been published in the scientific literature. MATERIALS AND METHODS: We reviewed pharmaco-economic methodology with special reference to cost-effectiveness analysis. We searched the literature for cost-effectiveness in blood product safety. RESULT: Net costs per quality adjusted life-year (QALY) gained varied from cost-saving for human immunodeficiency virus (HIV)- and hepatitis C virus (HCV) antibody screening and leucoreduction to several million US dollars per QALY gained for solvent-detergent treatment of plasma, nucleic acid amplification testing and HIV p24 antigen testing. CONCLUSIONS: To date the safety of blood transfusion has been largely determined by available technology, irrespective of pharmaco-economics. Net costs up to several million US dollars per QALY gained were found for interventions implemented.

Evaluation assays measuring platelet kinetics in bone marrow and peripheral blood. An overview.

Platelets play an important role in haemostasis and thrombosis. For an understanding of the pathophysiology and treatment of thrombocytopenia, it is not sufficient to measure only the platelet count. Platelet kinetic parameters, such as platelet survival and turnover, might be useful because many thrombocytopenia related disorders result from the interaction between production, utilization or destruction, and sequestration of platelets. Therefore, measuring platelet turnover with radiolabelled platelets could be a sensitive and qualitative tool for clinicians. However, the method does not enjoy widespread use because it has some serious drawbacks, such as the problems associated with the manipulation of blood and platelets, and the use of radioactivity. Recently, other useful assays for measuring platelet fluxes have been described in the literature, including plasma thrombopoietin and glycocalicin. In this review, these new tests will be described, compared with the classical method using radiolabelled platelets, and finally evaluated for their usefulness in clinical practice.

Effects of recombinant activated factor VII on coagulation measured by thromboelastography in liver transplantation.

Besides the conventional laboratory tests, thromboelastography (TEG) is used to monitor hemostasis during liver transplantation. A previous pilot study suggested a beneficial effect of recombinant activated factor VII (rFVIIa) on transfusion requirements in liver transplantation. In the present study, we assess the effects of rFVIIa on coagulation variables and TEG. In six study patients, the prothrombin time (PT), the activated partial thromboplastin time (aPTT) and TEG variables [reaction time (r), kinetic time (k), or clot formation time, alpha angle (alpha), and maximal amplitude (MA)] were recorded before and after the administration of a bolus of 80 microg/kg rFVIIa. These patients were compared with six controls who did not receive rFVIIa. In contrast with the control group, a significant shortening of PT (P = 0.028) and aPTT (P = 0.028), r (P = 0.046) and k (P = 0.043) values, and a significant incline of the alpha angle (P = 0.028) were noticed after injection of rFVIIa, whereas MA increased not significantly (P = 0.075). rFVIIa rapidly improved coagulation variables in liver transplant patients including PT and aPTT. Of the TEG variables, r, k and alpha angle significantly improved, and MA showed a trend to increase. These data suggest that rFVIIa not only influences the speed of clot formation, but also the physical properties of the clot, which cannot be detected by routine coagulation tests.

In vitro megakaryocyte expansion in patients with delayed platelet engraftment after autologous stem cell transplantation.

Increasing the number of megakaryocytic cells in stem cell transplants by ex vivo expansion culture may provide an approach to accelerate platelet engraftment after high-dose chemotherapy. However, it is unknown if a relationship exists between the expansion potential of progenitor cells and the time to platelet engraftment in vivo. Therefore, we questioned if those patients who potentially would benefit most from expanded cell supplements are able to generate megakaryocytic cells efficiently in vitro. The in vitro megakaryocyte proliferation was analyzed from 19 leukapheresis samples from a group of multiple myeloma patients who all showed rapid neutrophil engraftment, but varied from 7 to 115 days post-transplant to achieve platelet levels >20x10(9)/l. CD34+ cells were isolated and analyzed for their potential to form megakaryocytic colonies (CFU-Mk) in colony assays and megakaryocytic (CD61+) cells in suspension cultures. The frequency and size of CFU-Mk and the expansion potential of CD61+ cells varied eightfold between individual patients. A similar range was found with CD34+ cells isolated from normal bone marrow (n=9). Rapid platelet engraftment occurred in patients receiving both high or low CFU-Mk doses and with high and low expansion of CD61+ cells. Four patients who experienced prolonged (>3 weeks) thrombocytopenia received low CFU-Mk doses, but the expansion potential was around median values or higher. Therefore, we conclude that the megakaryocyte proliferation is not impaired and that in vitro expansion could increase the number of megakaryocytic cells, although other factors could be more relevant in platelet engraftment in this group of patients.