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Competing Interests: Competing interests: None declared.

A person's sexual and emotional life is greatly impacted after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This topic is not addressed very much by patients and caregivers. Physical, endocrine and genital chronic graft versus host disease (cGVHD)-related disorders are multiple and intertwined with psychological disorders. The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) has issued recommendations for a better gynecological monitoring of female recipients after allo-HCT. A patient booklet was also offered to patients in the form of questions and answers to facilitate discussions between patients and caregivers and to improve the management of sexual and emotional life after transplant.

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organises annual workshops in an attempt to harmonise clinical practices among different francophone transplantation centres. The SFGM-TC harmonisation workshops aim at establishing practical guidelines, on the one hand, from data from the literature and international recommendations and, on the other hand, by consensus in the absence of formally proven data. The sexual and emotional life of allogeneic hematopoietic stem cells transplanted (HSCT) patients is often very impacted and remains a subject relatively little addressed by patients and caregivers. This article is an update from a previous workshop and is accompanied by a patient booklet, which will be included in the post allograft follow-up workbook published by the SFGM-TC. The purpose of these two documents is to facilitate discussions between patients and caregivers on the subject and to present proposals for follow-up and tools to better manage the sexual and emotional life of allotransplanted patients., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Although studies of mixed chimerism following hematopoietic stem cell transplantation in patients with sickle cell disease (SCD) may provide insights into the engraftment needed to correct the disease and into immunological reconstitution, an extensive multilineage analysis is lacking. We analyzed chimerism simultaneously in peripheral erythroid and granulomonocytic precursors/progenitors, highly purified B and T lymphocytes, monocytes, granulocytes and red blood cells (RBC). Thirty-four patients with mixed chimerism and ≥12 months of follow-up were included. A selective advantage of donor RBC and their progenitors/precursors led to full chimerism in mature RBC (despite partial engraftment of other lineages), and resulted in the clinical control of the disease. Six patients with donor chimerism <50% had hemolysis (reticulocytosis) and higher HbS than their donor. Four of them had donor chimerism <30%, including a patient with AA donor (hemoglobin >10 g/dL) and three with AS donors (hemoglobin <10 g/dL). However, only one vaso-occlusive crisis occurred with 68.7% HbS. Except in the patients with the lowest chimerism, the donor engraftment was lower for T cells than for the other lineages. In a context of mixed chimerism after hematopoietic stem cell transplantation for SCD, myeloid (rather than T cell) engraftment was the key efficacy criterion. Results show that myeloid chimerism as low as 30% was sufficient to prevent a vaso-occlusive crisis in transplants from an AA donor but not constantly from an AS donor. However, the correction of hemolysis requires higher donor chimerism levels ( i.e ≥50%) in both AA and AS recipients. In the future, this group of patients may need a different therapeutic approach., (Copyright© 2020 Ferrata Storti Foundation.)

Allogeneic stem cell transplantation remains the only curative treatment for sickle cell anemia (SCA), but the place of myeloablative conditioning in the procedure remains to be defined. The aim of the present study was to analyze long-term outcomes, including chimerism, SCA-related events and biological data (hemoglobin, reticulocytes, HbS%), and fertility in a French series of 234 SCA patients under 30 years of age who, from 1988 to 2012, received a matched-sibling-donor stem cell transplantation following standardized myeloablative conditioning [busulfan, cyclophosphamide and rabbit antithymocyte globulin (ATG)]. Since the first report of the series (1988-2004), 151 new consecutive patients with SCA have been similarly transplanted. Considering death, non-engraftment or rejection (donor cells <5%) as events, the 5-year event-free survival was 97.9% (95% confidence interval: 95.5-100%), confirming, since the year 2000, an at least 95% chance of cure. In the overall cohort (n=234, median follow up 7.9 years), event-free survival was not associated with age, but chronic-graft- versus -host disease (cGvHD) was independently associated with recipient's age >15 years (hazard ratio=4.37; P =0.002) and lower (5-15 vs 20 mg/kg) ATG dose (hazard ratio=4.55; P =0.001). At one year, 44% of patients had mixed chimerism (5-95% donor cells), but those prepared with ATG had no graft rejection. No events related to SCA occurred in patients with mixed chimerism, even those with 15-20% donor cells, but hemolytic anemia stigmata were observed with donor cells <50%. Myeloablative transplantation with matched-sibling donor currently has a higher event-free survival (98%) in patients under 30 years of age than that reported for non-myeloablative conditioning (88%). Nevertheless, the risk of cGvHD in older patients and the need to preserve fertility might be indications for a non-myeloablative conditioning., (Copyright© 2020 Ferrata Storti Foundation.)

Study Question: How efficacious is transplantation of ovarian cortex previously exposed to chemotherapy?, Summary Answer: Prior exposure to chemotherapy did not disrupt the function of cryopreserved ovarian tissue after transplantation., What Is Known Already: Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) is an efficacious technique for restoration of female fertility. At least 130 children have been born following this procedure. To date, little is known about the efficacy of OTT in patients exposed to cancer chemotherapy prior to OTC., Study Design, Size, Duration: This study evaluates the recovery of ovarian function and fertility in 31 consecutive patients who had received OTT, between 2005 and 2015., Participants/materials, Setting, Methods: Thirty one patients, wanting children, were transplanted with autologous ovarian cortex, among which 22 patients (71%) had been exposed to chemotherapy before OTC. Recovery of ovarian function was considered total once menstruation occurred. Ovarian function recovery (OFR), ovarian graft survival, and incidence of pregnancy were related to previous chemotherapy exposure, type of chemotherapy and graft characteristics (number of grafted fragments and follicular density)., Main Results and Role of Chance: The amount of ovarian tissue collected was the only parameter to show any significant change between patients with versus without previous chemotherapy. At 1 year after OTT, the cumulative incidence of OFR was 83% (93% in patients exposed to chemotherapy and 67% in others (P = 0.14)). A low follicular density (<0.3 foll/mm2) in the transplant and a low number of grafted fragments (<16) were significantly associated with a delayed OFR. Graft survival at 2 years after OTT was 77%. It was significantly lower in patients exposed to bifunctional alkylating agents before ovarian cryopreservation and in patients with a low follicular density. The proportion of women who succeeded in having at least one live birth was 23% in the total population, 0% (0/9) in the group 'no previous chemotherapy', and 32% (7/22) in the group 'previous chemotherapy'. The cumulative incidence of pregnancy (Kaplan-Meier) at 3 years after OTT was 36% overall and 49% in case of previous chemotherapy, with no difference related to previous chemotherapy exposure. In total there were 13 pregnancies and 8 births in 7 patients., Limitations, Reasons for Caution: The pathology in the two groups of patients was not comparable. In the group of patients who had chemotherapy before OTC, there were 95% of hematological malignancies. In the group of patients who did not have chemotherapy before OTC only 1 out of 9 patients had a malignant hematological disease while 44% had some pathology affecting the ovaries. Few women are available for study and only large changes are likely to have statistical significance., Wider Implications of the Findings: These results suggest that prior cancer chemotherapy should no longer be considered a limitation to cryopreservation of ovarian tissue and current recommendations in this regard should be revised., Study Funding/competing Interest(s): This study was supported by the Agence de la Biomédecine (France's biomedical office). There are no competing interests to report., Trial Registration Number: NCT02184806., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Dynamic conformal radiotherapy with helical TomoTherapy ® (HT) offers a more quantitative paradigm for total body irradiation. Treatment planning, delivery, dose verification of the first French experiences of total body irradiation using helical TomoTherapy ® are presented., Materials and Methods: Patients planned for total body irradiation at our institution from February 2012 to May 2013 were reported. Total body irradiation consisted in a single fraction of 2Gy. Planning target volume was divided in two due to the limited translation length of the table. Delivery quality assurance was performed with cylindrical phantom, ionization chamber and films. Thermoluminescent dosimeters and radiochromic films were used for in vivo dosimetry and junction region heterogeneity assessment., Results: Six patients were included. One finally did not receive the treatment but dosimetric data were analyzed. Planned V 95% was covered by D 95% and V 2% did not exceed D 107% for five of the six patients. The mean relative difference between measured and calculated absolute dose of the Delivery quality assurance was always less than 2.5% (mean value±SD: 1%±0.67%). Gamma index (3%; 3mm) was less than 1 for at least 93% of the points (value±SD: 97.4±1.6% and 96.6±2.5% for upper and lower part of treatment respectively). Difference between in vivo measured and calculated dose was above 5% for only two out of 15 points (maximum: 10.2%, mean: 0.73±4.6%). Junction region heterogeneity was in average 5.8±1%. The total treatment session of total body irradiation lasted 120min, with a mean beam on time of 17.2±0.6 and 11.2±1.6min for upper and lower part of the body respectively., Conclusion: Total body irradiation using helical TomoTherapy ® guaranteed high dose homogeneity throughout the body and dose verification was achievable, showing small difference between planned and delivered doses., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

The not-for-profit issue has been debated in November 2016 in Paris; this issue is one of the four canonical pillars of ethical blood donation. It is intimately bound to benevolence though it is distinct, as not-for-profit calls for institutions while benevolence calls for individuals. It is indeed intended that voluntary blood donors do not benefit from their donation and are thus non-remunerated. Not-for-profit is essential since it refers to the public character of blood as a putative public resource aimed at being shared as a tribute of solidarity. A central question however is linked to the capacity- or not -of public sectors to ensure that blood components are universally available, with special mention to plasma derived drugs, without the contribution of the for profit, private sector., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Treatment of steroid-resistant acute graft-versus-host disease (GVHD) remains an unmet clinical need. Inolimomab, a monoclonal antibody to CD25, has shown encouraging results in phase 2 trials. This phase 3 randomized, open-label, multicenter trial compared inolimomab vs usual care in adult patients with steroid-refractory acute GVHD. Patients were randomly selected to receive treatment with inolimomab or usual care (the control group was treated with antithymocyte globulin [ATG]). The primary objective was to evaluate overall survival at 1 year without changing baseline allocated therapy. A total of 100 patients were randomly placed: 49 patients in the inolimomab arm and 51 patients in the ATG arm. The primary criteria were reached by 14 patients (28.5%) in the inolimomab and 11 patients (21.5%) in the ATG arms, with a hazard ratio of 0.874 (P = .28). With a minimum follow-up of 1 year, 26 (53%) and 31 (60%) patients died in the inolimomab and ATG arms, respectively. Adverse events were similar in the 2 arms, with fewer viral infections in the inolimomab arm compared with the ATG arm. The primary end point of this randomized phase 3 trial was not achieved. The lack of a statistically significant effect confirms the need for development of more effective treatments for acute GVHD. This trial is registered to https://www.clinicaltrialsregister.eu/ctr-search/search as EUDRACT 2007-005009-24., (© 2017 by The American Society of Hematology.)

Cancer medicines: reasons for anger. The recent emergence of innovative therapeutics in oncology parallels growing concerns about their soaring prices. In the USA, this rapid inflation has already resulted in major inequalities in the access to cancer care and in the development of the so-called "financial toxicity", whereas in France it could dangerously threaten the social insurance system. According to the pharmaceutical industries, high prices are primarily justified by major investments in research and development but recent paradigmatic changes in this sector (rationalization of target identification, frequently originating from academic research teams, accelerated or conditional registration procedures, precision medicine with molecular-driven rather than histology-based indication, and large dissemination of immunotherapies) are challenging such a perspective. In this context, physicians, civil society and patients are increasingly supporting transparency in a fair process of drug pricing., Competing Interests: A. Gonçalves déclare des liens d’intérêts sans rapport avec cette publication : invitations à des congrès (Roche, Novartis, Amgen, Pfizer) et des rémunérations personnelles comme consultant (Roche, Novartis) ou pour des interventions dans des conférences (Roche, Novartis, EISAI). D. Maraninchi et J.-P. Vernant déclarent n’avoir aucun lien d’intérêts.

Detection of increasing mixed chimerism (IMC) using standard PCR correlates with relapse after allo-SCT for acute leukemias (ALs). Quantitative real-time PCR of insertion/deletion polymorphism (indel qrtPCR) is a much more sensitive method, which can be performed on peripheral blood. We studied the significance of low increases of recipient cells (0.1%) detected by indel qrtPCR in a cohort of 89 transplants. We did not observe relapse among the 32 patients with no IMC. Fifty-seven patients presented a first IMC, which was followed by four different scenarios: a decreasing MC (26 cases, no relapse), a stable MC (1 case, 1 relapse), a second IMC (24 cases, 15 relapse) or no control of chimerism (6 cases, 5 relapses). In multivariate analysis, detection of two successive IMCs was strongly associated with relapse (hazard ratio (HR): 9.4, 95% confidence interval (CI): 3.8-23; P<0.0001). Among the 57 patients who presented at least one IMC, 27 underwent immunomodulation (tapering of immunosuppression or donor lymphocyte injection), leading to a 1-year relapse rate of 15.7% vs 57.6% in the 30 other patients (P=0.0007). Altogether, these results indicate that chimerism analysis using indel qrtPCR in peripheral blood is a useful tool for detection of relapse in patients transplanted for AL.

Background: The aim of this study was to investigate the impact of the high-dose regimen on the outcome of patients with follicular lymphoma (FL) having had autologous stem-cell transplantation (ASCT) in a recent time period., Patients: Between 1995 and 2007, 2233 patients with FL had their first ASCT with either a total body irradiation (TBI)-containing regimen or carmustin, etoposide, cytarabine and melphalan (BEAM), of which 47% were autografted in first remission., Results: After a median observation time of 73 months (interquartile range 30-107), 5- and 10-year non-relapse mortality (NRM) was similar (6% and 10% in both groups). No significant NRM differences became evident after multivariate adjustment for confounders. Secondary malignancies were observed in 9.7% and 7.9% of the patients after TBI and BEAM (P = 0.19), which were treatment-related myelodysplastic syndromes/acute myelogenous leukaemia (t-MDS/AML) in 3.4% and 2.8% (P = 0.57). The median time to t-MDS/AML was around 50 months in both groups. Because of a lower relapse incidence, TBI was associated with better event-free survival reaching statistical significance in the patients transplanted in first remission but not in those transplanted beyond first remission., Conclusions: In patients with FL who received TBI-based ASCT after 1995 increased NRM and t-MDS/AML risks did not emerge compared with BEAM while disease control was at least equivalent., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In acquired thrombotic thrombocytopenic purpura (TTP), the persistence of severe ADAMTS13 deficiency (<10%) during remission is associated with more relapse. Preemptive (ie, after remission) administration of rituximab in these patients to prevent relapses remains controversial. We performed a cross-sectional analysis of 12-year follow-up data to compare the relapse incidence with or without preemptive rituximab infusion. Among 48 patients who experienced at least one episode of acquired TTP followed by severe ADAMTS13 deficiency during remission, 30 received preemptive rituximab (group 1); the other 18 did not (group 2). After a median of 17 months (interquartile range [IQR], 11-29) following rituximab, the relapse incidence decreased from 0.57 episodes/year (IQR, 0.46-0.7) to 0 episodes/year (IQR, 0-0.81) (P < .01) in group 1. ADAMTS13 activity 3 months after the first rituximab infusion increased to 46% (IQR, 30%-68%). Nine patients required additional courses of rituximab. In 5 patients, ADAMTS13 activity failed to increase durably. Four patients experienced manageable adverse effects. In group 2, the relapse incidence was higher (0.5 relapses/year; IQR, 0.12-0.5; P < .01). Relapse-free survival was longer in group 1 (P = .049). A persistent severe ADAMTS13 deficiency during TTP remission should prompt consideration of preemptive rituximab to prevent relapses., (© 2014 by The American Society of Hematology.)

With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, as assessed by immunoglobulin/T-cell receptor minimal residual disease (MRD) levels. The study was performed in 423 younger adults with Philadelphia chromosome-negative ALL in first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative incidence of relapse (CIR) as the primary end point. In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. A higher specific hazard of relapse was independently associated with postinduction MRD level ≥10(-4) and unfavorable genetic characteristics (ie, MLL gene rearrangement or focal IKZF1 gene deletion in BCP-ALL and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene alteration in T-cell ALL). These 2 factors allowed definition of a new risk classification that is strongly associated with higher CIR and shorter relapse-free and overall survival. These results indicate that genetic abnormalities are important predictors of outcome in adult ALL not fully recapitulated by early response to therapy. Patients included in this study were treated in the multicenter GRAALL-2003 and GRAALL-2005 trials. Both trials were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively., (© 2014 by The American Society of Hematology.)

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.

We report here the results of the GRAAPH-2003 trial with long-term follow-up in 45 patients with de novo Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Imatinib-based strategy improved the 4-year overall survival (OS) up to 52% versus 20% in the pre-imatinib LALA-94 trial (P = .0001). Despite the selection in patients who actually underwent transplantation, these results suggest that allogeneic or autologous stem cell transplants (SCTs) still have a place in overcoming the poor prognosis of Ph+ ALL in the era of imatinib therapy. OS was 50% after allogeneic SCT (24 patients), 33% in patients without a transplantation (9 patients), and 80% after autologous SCT (10 patients without allogeneic donor or >55 years, including 7 patients in complete molecular response)., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The correlation between the incidence of GVHD and the number of infused CD34(+) cells remains controversial for PBSC transplantation after a reduced-intensity-conditioning (RIC) regimen. We evaluated 99 patients transplanted with an HLA-identical sibling after the same RIC (2-Gy-TBI/fludarabine). Donor and recipient characteristics, donor's blood G-CSF-mobilized CD34(+) cell count, and number of infused CD34(+) and CD3(+) cells were analyzed as risk factors for acute and chronic GVHD There was a trend for an increased incidence of extensive chronic GVHD in the quartile of patients receiving more than 10 × 10(6) CD34(+) cells/kg (P = 0.05). Interestingly, the number of donor's blood CD34(+) cells at day 5 of G-CSF mobilization was closely associated with the incidence of extensive chronic GVHD, that is, 48% (95% CI: 28-68) at 24-months in the quartile of patients whose donors had the highest CD34(+) cell counts versus 24.3% (95% CI: 14-34) in the other patients (P = 0.007). In multivariate analysis, the only factor correlating with extensive chronic GVHD (cGVHD) was the donor's blood CD34(+) cell count after G-CSF (HR 2.49; 95% CI: 1.16-5.35, P = 0.019). This study shows that the incidence of cGVHD is more strongly associated with the donor's ability to mobilize CD34(+) cells than with the number of infused CD34(+) cells.

Objective: To assess the efficacy and safety of rituximab in adults responding poorly to standard treatment for severe autoimmune thrombotic thrombocytopenic purpura., Design: Open-label prospective study. Outcomes in the survivors were compared to those of 53 historical survivors who were given therapeutic plasma exchange alone or with vincristine., Setting: Hospitals belonging to the Reference Network for Thrombotic Microangiopathies in France., Patients: Twenty-two adults with either no response or a disease exacerbation when treated with intensive therapeutic plasma exchange., Intervention: Add-on rituximab therapy, four infusions over 15 days., Measurements and Main Results: One patient died despite two rituximab infusions. In the rituximab-treated patients, the time to a durable remission was significantly shortened (p = .03), although the plasma volume required to achieve a durable remission was not significantly different compared to the controls. Platelet count recovery occurred within 35 days in all 21 survivors, compared to only 78% of the historical controls (p < .02). Of the rituximab-treated patients, none had a relapse within the first year but three relapsed later on. In patients treated with rituximab, a rapid and profound peripheral B-cell depletion was produced, lasting for 9 months and correlating with higher a disintegrin and metalloproteinase with thrombospondin-13 activity and lower anti-a disintegrin and metalloproteinase with thrombospondin-13 antibody titers. These differences were no longer significant after 12 months. No severe side effects occurred., Conclusions: Adults with severe thrombocytopenic purpura who responded poorly to therapeutic plasma exchange and who were treated with rituximab had shorter overall treatment duration and reduced 1-yr relapses than historical controls.

Purpose: Preliminary clinical experience has suggested that radiation therapy (RT) may be effectively incorporated into conditioning therapy before transplant for patients with refractory/relapsed malignant lymphoma. We investigated the feasibility of debulking selective lymph node irradiation before autologous and/or allogeneic stem cell transplantation (SCT) using helical tomotherapy (HT)., Methods and Materials: Six consecutive patients with refractory malignant lymphoma were referred to our institution for salvage HT before SCT. All patients had been previously heavily treated but had bulky residual tumor despite chemotherapy (CT) intensification. Two patients had received previous radiation therapy. HT delivered 30-40 Gy in the involved fields (IF), using 6 MV photons, 2 Gy per daily fraction. Total duration of treatment was 28 to 35 days., Results: Using HT, doses to critical organs (heart, lungs, esophagus, and parotids) were significantly decreased and highly conformational irradiation could be delivered to all clinical target volumes. HT delivery was technically possible, even in patients with lesions extremely difficult to irradiate in other conditions or in patients with previous radiation therapy. No Grade 2 or higher toxicity occurred. Four months after the end of HT, 5 patients experienced complete clinical, radiologic, and metabolic response and were subsequently referred for SCT., Conclusions: By more effectively sparing critical organs, HT may contribute to improving the tolerance of debulking irradiation before allograft. Quality of life may be preserved, and doses to the heart may be decreased. This is particularly relevant in heavily treated patients who are at risk for subsequent heart disease. These preliminary results require further prospective assessment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Bronchiolitis obliterans (BO) is a severe complication of hematopoietic stem cell transplantation (HSCT). It is considered as a respiratory manifestation of chronic graft-versus-host disease. It is quite similar to the bronchiolitis obliterans after lung transplantation. Classical therapy associates steroids and immunosuppressive drugs, however theses procedure showed a modest efficacy and have an important morbidity. Recent progresses in the physiopathology of BO post-HSCT allow to use new treatments: mTOR inhibitors, immunotherapy, extra-corporeal photochemotherapy, and bronchial anti-inflammatory effects of azithromycin, statins or antileucotriens. This review will focus on the use of these new therapies in BO post-HSCT., (2011 Elsevier Masson SAS. All rights reserved.)

Background: Allogeneic donor natural killer (NK)-cell infusion (NK-DLI) is a promising immunotherapy for patients with hematologic disorders., Case Report: This report describes the case of a patient who received a single haploidentical NK-DLI for a relapse of acute myeloid leukemia (AML) after haploidentical hematopoietic stem cell transplantation. He underwent a cytoreductive, immunosuppressive regimen before NK-DLI and received high-dose interleukin-2 in vivo for 8 weeks afterward., Results: No major adverse effect was observed. Prospective phenotypic and functional studies of the NK cells showed major expansion of infused NK cells and, more importantly, of the alloreactive KIR2DL1+KIR2DL2/DL3-NKG2A- subset, which reached 117×10(6) cells/L on Day +14 after NK-DLI, the greatest expansion of infused alloreactive NK cells reported so far. Infused NK cells conserved their lytic capacities against K562 target cells and primary AML-mismatched blasts., Conclusion: We review the literature to clarify these data and to detail the indications for allogeneic NK-DLI, the criteria for determining the most suitable donor, the types of conditioning regimens, and the procedures for selecting and activating NK cells., (© 2011 American Association of Blood Banks.)

Purpose: To analyze the outcome, including nonrelapse mortality (NRM), relapse rate (RR), progression-free survival (PFS), and overall survival (OS), of patients with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) relapsed after an autologous stem-cell transplantation (ASCT) and treated with an allogeneic stem-cell transplantation (allo-SCT)., Patients and Methods: The European Group for Blood and Marrow Transplantation database was scanned for a first allo-SCT in relapsed DLBCL after a previous ASCT between 1997 and 2006. Other inclusion criteria were age at allo-SCT ≥ 18 years and availability of an HLA-identical sibling or a matched unrelated donor. A total of 101 patients (57 males; median age, 46 years) were included. Median follow-up for survivors was 36 months., Results: Myeloablative conditioning regimen was used in 37 patients and reduced intensity conditioning (RIC) was used in 64 patients. Three-year NRM was 28.2% (95% CI, 20% to 39%), RR was 30.1% (95% CI, 22% to 41%), PFS was 41.7% (95% CI, 32% to 52%), and OS was 53.8% (95% CI, 44% to 64%). NRM was significantly increased in patients ≥ 45 years (P = .01) and in those with an early relapse (< 12 months) after ASCT (P = .01). RR was significantly higher in refractory patients (P = .03). A time interval to relapse after ASCT of < 12 months was associated with lower PFS (P = .03). The use of RIC regimens was followed by a trend to a lower NRM (P = .1) and a trend to a higher RR (P = .1), with no differences in PFS and OS. No differences were seen between HLA-identical siblings and matched unrelated donors., Conclusion: Allo-SCT in relapsed DLBCL after ASCT is a promising therapeutic modality. Patients with a long remission after ASCT and with sensitive disease at allo-SCT are the best candidates for this approach.

The subpopulation of regulatory T cells (Treg) was shown to play a key role in alloreactive responses. In allogeneic hematopoietic stem cell transplantation, several groups tested whether Treg content in transplants correlates with graft-versus-host disease (GVHD) with controversial results. In a retrospective study of 49 consecutive HLA-matched sibling transplantations, we studied the relationship between Treg content in bone marrow transplants and acute GVHD (aGVHD) occurrence. We observed a large variability in Treg in bone marrow grafts. However, contrary to previous observations in peripheral blood stem cells transplantation, we report that the Treg content of allogeneic bone marrow transplantation did not predict the occurrence of aGVHD., (Copyright © 2011. Published by Elsevier Inc.)

Background: Some patients demonstrate delayed recoveries after autologous hematopoietic stem cell transplantation despite infusion of an adequate number of CD34+ cells/kg and clinically stable status. Factors considered being possible predictors of this outcome in this context were explored., Study Design and Methods: A total of 246 patients were evaluated in terms of engraftment. Delayed recovery was defined by white blood cell recovery time exceeding mean+1 SEM. Clinical factors and graft characteristics were examined. Comparisons between patients with normal or delayed engraftment were made. Proinflammatory cytokines and proteolytic enzyme quantification and CXCR4+ and CD44+ cell enumeration were performed on peripheral hematopoietic stem cells (PHSC) product samples of patients with delayed engraftment and patients with usual engraftment time., Results: Sixteen patients, who received at least 3 × 10(6) CD34+ cells/kg without known clinical factors likely to affect engraftment, demonstrated a delayed recovery time of over 20 days. Some graft variables were found to be significantly increased in these patients by univariate analysis. One variable was the total number of nucleated cells cryopreserved and infused. Among the nucleated cells, the absolute number of granulocytes before and after cryopreservation also differed significantly between the two groups. A multivariate analysis showed that the main predictive factor for delayed recovery was the number of nucleated cells in the graft (p=0.0044). The influence of contaminating cells might be related to the release of elastase, matrix metalloproteinase-9, interleukin (IL)-1β, and IL-6 involved in stem cell homing., Conclusion: Therefore, the numeration of total nucleated cells and granulocytes should be considered as a possible quality control variable of PHSCs submitted for cryopreservation., (© 2010 American Association of Blood Banks.)