Background: Hematopoietic Stem Cell transplantation (HSCT) is a potentially curative treatment for several hematological diseases, but it is often complicated by significant morbidity and mortality. This is particularly related to chronic Graft versus Host Disease (GVHD) that can deeply impact patients’ quality of life (QoL). Aims: Our purpose was to evaluate patients’QoL after HSCT and to clarify the impact of chronic GVHD. Methods: We conducted a cross-sectional descriptive study at the National Bone Marrow Transplant Center including patients who underwent HSCT between January 2018 and December 2019. These patients filled in the questionnaire for the quantitative measurement of quality of life using 36-Item Short-Form Health Survey (SF-36) and to the Functional Assessement of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) during a phone interview. Results: Of the 52 patients still alive at the time of the survey, 43 patients were contactable and willing to participate (participation rate: 83%). The median age of the participants was 28 years (7-52) with a sex ratio of 1.52. Underlying disease was acute leukemia for 29 patients and aplastic anemia for 14 others. The median time between HSCT and the interview was of 26 months (17-39). At the time of the survey, all patients were in complete remission and 28% among them (12 of 43) had active extensive chronic GVHD. Results obtained in the different dimensions of the SF-36 and FACT-BMT scales indicated good overall QoL in patients after HSCT. However, using SF-36, patients with chronic active GVHD had significantly lower scores on « role limitation due to their physical condition » (p=0.001), «role limitation due to their psychological condition » (p=0.0001), « vitality » (p= 0.045) and « general health perception » (p=0.027) than the other patients. In addition, the FACT-BMT score revealed a negative impact on chronic GVHD in physical well-being dimension (p=0.009) and the functional well-being dimension (p=0.027). Apart from chronic active GVHD, a negative impact on QoL was noted with: adult age, peripheral stem cells transplants and GVHD prophylaxis with ciclosporin alone. Summary/Conclusion: Active chronic GVHD was associated with impared QoL in patients after HSCT hence the need for rapid diagnosis and optimal prophylaxis and treatment of this complication.

Background: Cryopreservation of hematopoietic stem cells (HSC) is associated with variable loss of CD34+ graft richness. Aims: Our aim was to examine the validity of measuring CD34 richness on flow cytometry from cryotubes before thawing infusing bags in order to reduce risks associated with low-quality grafts. Methods: CD34+ cells richness was analyzed on flow cytometry in leukapheresis procedures before freezing and after thawing. Data from control cryotubes were compared to those from infusing bags using Wilcoxon signed-rank test. Results: Between October 2017 and November 2020, 129 patients underwent HSC autologous transplantation in our department for multiple myeloma (n=94) or Hodgkin and non-Hodgkin lymphoma (n=35). The mean time from mobilization to HSC transplantation was 3.3 months (0-11).The median age was 52 years (11-66) with a sex ratio of 1.4. We analyzed 154 infusion bags. The mean amount of CD34+ cells on flow cytometry was respectively 3.2 x 10⁶/kg (0.39-19.95) and 1.86 x 10⁶/kg (0.16-21.58) per bag before cryopreservation and after thawing, corresponding to a cell loss of 40% (p=0.008). The mean CD34+ cell richness found in cryotubes after thawing was 1.7x 10⁶/kg (0-21.09), concordant with that found in the infusing bags after thawing (p=0.132). The positive predictive value (PPV) of cryotubes (CD34+ cells richness in infusing bag greater than 2 x 10⁶/kg when cryotube richness is greater than 2 x 10⁶/kg) was 70% and the negative predictive value (NPV) was 71%. Cryopreservation duration >3 months did not alter the predictive value of cryotubes (PPV=71%, NPV=68%). The PPV was lower for patients older than 50 years (60%) and for patients treated for lymphoma (50%) compared to those younger than 50 years (82%) and treated for multiple myeloma (75%). No delayed engraftment was noted in our cohort regardless of CD34+ richness in the cryotube. Summary/Conclusion: Cryotube used to evaluate CD34+ richness prior to reinfusion is not informative enough although its predictive value may differ according to the age and the underlying disease.

Background: Peripheral T-cell lymphoma (PTCL) is a rare heterogeneous lymphoma with a poor long-term survival. Aims: Our purpose was to assess the efficacy and prognosis of autologous stem cell transplantation (ASCT) as a frontline treatment for PTCL. Methods: Patients (pts) with primary diagnosed PTCL received 6–8 weeks of pre transplant induction chemotherapy. If in complete or partial remission, they proceeded to consolidation with BEAM based ASCT. We retrospectively analyzed all consecutive patients with PTCL treated with ASCT in the Tunisian National Center of Bone Marrow transplantation from January 2004 to February 2017. PTCL diagnosis confirmed by immunohistochemistry according to 2016 WHO classification criteria. Results: In all, 32 pts were enrolled. Median age at ASCT was 41 years (range 24 to 60 years) and 23 patients (72%) were male. PTCL subtypes included ALK-negative anaplastic T cell lymphoma (TCL) (n = 12); PTCL not otherwise specified, (n = 9); angioimmunblastic TCL (n = 2); enteropathy type TCL (n = 2); extra nodal natural killer TCL, nasal type (n = 2); and hepato splenic TCL (n = 2). 81.2% had advanced disease (Ann Arbor stage III or IV). Three patients (9,4%) had bone marrow involvement and 47 % had elevated serum lactate dehydrogenase. 72 % of all patients had a good PS (WHO 0 to 1). According to IPI, pts were classified low risk (33%), low intermediate (53%) or high intermediate (13%). Pre-transplant first line chemotherapy was CHOP/CHOEP regimen (60%) or ACVBP regimen (40%). 30% of pts had refractory disease and received second line chemotherapy. Pts achieved CR (61%) or PR (39%) prior to ASCT. The median time to neutrophil engraftment was 9 days (range 7 to 16) and the median time to platelet engraftment was 11 days (range 6 to 18). The median hospital stay was 33 days (range 17 to 99). After a median follow-up post ASCT of 23 months (range 5 to 150), 12 patients remained alive. The main cause of death was lymphoma progression (73%). Non-relapse mortality was 3%. The 5-year DFS and OS rate was 35% and 38% respectively. Patients transplanted in CR had a 5-year OS rate of 42%, compared with an OS of 31% in patients in PR. Summary/Conclusion: Frontline ASCT following conventional chemotherapy in PTCL is safe and may be beneficial

Background: Renal failure (RF) is a common complication of multiple myeloma found in 25% at diagnosis and in 50% during the course of the disease. RF persistence after induction treatment may constitute a factor of ineligibility for autologous stem cell transplantation (ASCT). However, its impact on toxicity and survival post-ASCT is still subject to discussion. Aims: We aimed to compare the toxicity and survival after ASCT in newly diagnosed multiple myeloma (NDMM) patients (pts) with or without RF at diagnosis Methods Retrospective comparative study of two groups of NDMM pts without RF at diagnosis (Group 1: G1) or with RF at diagnosis (Group 2: G2). These patients were treated according to the Tunisian national referential by dexamethasone, thalidomide +/- bortezomib and transplanted at the hematology department of the national center of bone marrow transplant between January 2011 and December 2016. The IMWG 2014 and IMWG 2016 response criteria were used to assess hematologic and renal response respectively. Results: Data from 134 patients were analyzed. Median age at ASCT was 54 years (range, 25-65). Sex ratio was 1.2. In all, 114 (85%) and 20 (15%) pts were included in G1 and G2 respectively. In G2, 13 pts (65%) had severe renal impairment at diagnosis; 2 of them required at least one dialysis session. After induction, renal response was complete (70%), partial (15%) or minor (15%). As a pre-transplant conditioning, all pts in G1 received melphalan (MEL) at the dose of 200 mg/m2. In G2, pts received either MEL 200 mg/m2 (85%) or MEL 140 mg/m2 (15%). The two comparative groups were matched with regards to preASCT patient's characteristics and hematological status. In G2 compared to G1, risk of grade ≥3 mucositis (100 vs 51%) was significantly higher, while no significant differences were found in duration of neutropenia (medians 6 vs 6 days), microbiologically documented infection (31 vs 26%), duration of hospitalization (medians: 23 vs 23 days), post-transplant response (ORR; 75 vs 87%), time to progression (median 20 vs 19 months), 5-year PFS (34vs 33%) and OS (61 vs 59%) Summary/Conclusion: Apart from mucositis, ASCT in MM with or without RF was associated with a comparable toxicity and survival rate

Background:Cytomegalovirus (CMV) infection is a major complication after allogeneic stem cell transplantation (ASCT).Aims:The aim of the study was to evaluate the impact of CMV reactivation on the relapse rate after ASCT in patients with acute myeloid leukemia (AML).Methods:Retrospective study conducted in patients with AML who underwent ASCT from HLA identical sibling donor between January 2011 and December 2018. Conditioning regimen consisted of Busulfex and Cyclophosphamide (Bu/Cy) or Fludarabine and Busulfex (F/Bu). Graft‐versus‐host disease (GVHD) prophylaxis consisted of cyclosporine and a short course of methotrexate. Antiviral prophylaxis for CMV infection was assured by Acyclovir from day +1 to day +180. CMV detection was carried out once‐a‐week from engraftment to day +100 by either pp 65 antigenemia test or real‐time quantitative PCR.Results:Ninety‐three patients were enrolled (55 men and 38 women). Median age was 33 years (range, 5 ‐ 49 y). At the time of transplant, 73 patients (78.5%) were in CR1, 16 patients (17.2%) were in CR2 and 4 patients (4.3%) were in response failure. CMV serostatus for donor (D) and recipient (R) was available for 44 cases (47.3%). Serostatus of R+/D+ and R+/D− was observed in 38 patients (86.4%). Stem cell source were BM in 49 cases (52.7%) and PBSC in 44 cases (47.3%). No graft failure was observed. Acute GVHD grade II‐IV occurred in 19 patients (20.4%). Chronic GVHD was observed in 40 patients (45.4%). Twenty‐nine patients (31.2%) developed CMV reactivation. With a median follow‐up of 2 years (range 49 days – 7 years), the overall survival (OS) and the non‐relapse mortality (NRM) were not statistically significant between patients with CMV reactivation and those without CMV reactivation (74% vs 63%, p = 0.3 and 20.7% vs 7.8%, p = 0.08, respectively). Twenty‐four patients (25.8%) relapsed at a median of 6 months (range 2 ‐ 67 months). the rate of relapse among patients with CMV reactivation was significantly lower than in those without CMV reactivation (10.3% vs 32.8%, p = 0.02). In univariate analysis, the CMV reactivation was the only factor associated with a decreased risk of relapse (OR = 0.23, 95% CI: 0.06–0.87, p = 0.02).Summary/Conclusion:CMV reactivation was associated with decreased relapse risk after ASCT for patients with AML without a benefit in OS.

To describe the hematopoietic stem cell transplantation (HSCT) activities for children in the Eastern Mediterranean (EM) region, data on transplants performed for children less than 18 years of age between 1984 and 2011 in eight EM countries (Egypt, Iran, Jordan, Lebanon, Oman, Pakistan, Saudi Arabia and Tunisia) were collected. A total of 5187 transplants were performed, of which 4513 (87%) were allogeneic and 674 (13%) were autologous. Overall, the indications for transplantation were malignant diseases in 1736 (38.5%) and non-malignant in 2777 (61.5%) patients. A myeloablative conditioning regimen was used in 88% of the allografts. Bone marrow (BM) was the most frequent source of stem cells (56.2%), although an increasing use of PBSC was observed in the last decade. The stem cell source of autologous HSCT has shifted over time from BM to PBSC, and 80.9% of autologous HSCTs were from PBSCs. The donors for allogeneic transplants were matched-related in 94.5% of the cases, and unrelated transplants, mainly cord blood (99%) in 239 (5.5%) cases. This is the first report to describe the pediatric HSCT activities in EM countries. Non-malignant disorders are the main indication for allogeneic transplantation. Frequency of alternate donor transplantation is low.

This study compared retrospectively the effectiveness, toxicity and hematopoietic recovery after autologous peripheral blood stem cell transplantation (ASCT) of two consecutive peripheral blood stem cell mobilization regimens in newly diagnosed MM patients. Patients in group 1 (n=178) were treated with 4 g/m2 of cyclophosphamide (CY) plus G-CSF (5 μg/kg/day). Patients in group 2 (n=117) with 750 mg/m2 of VP16 plus G-CSF (10 μg/kg/day). Optimal mobilization, defined by a target number of 8 × 106 CD34+ cells/kg collected, was achieved in 62.4% and 89.7% of patients in groups 1 and 2, respectively (P<10−4). The median number of aphaeresis sessions was reduced from two in group 1 to one in group 2 (P<10−4). Grade4 neutropenia, febrile neutropenia and IV antibiotic use were significantly more frequent in group 1 than in group 2 (P<10−4). Red blood cell transfusion requirements were significantly greater in group 1 (P=0.007). The switch to VP16-G-CSF10 resulted in a significant reduction of the number of hospitalization days (P<10−4). Neutrophil and platelet recovery after ASCT occurred on days 11 and 12, respectively, in the two groups with no significant differences. VP16+G-CSF10 allowed liberation of resources in the clinical and aphaeresis departments and demonstrated a better effectiveness-safety profile than CY+G-CSF5.

Candida parapsilosis est une levure saprophyte de la peau, caractérisée par son affinité pour les cathéters, responsable d’un large éventail de manifestations cliniques dont les candidémies, infections de pronostic redoutable. C’est un complexe génétiquement hétérogène comportant trois groupes distincts : Candida parapsilosis (groupe I), Candida orthopsilosis (groupe II) et Candida metapsilosis (groupe III), phénotypiquement identiques. L’objectif de notre travail était l’étude épidémiologique de ce complexe de levures en identifiant les souches correspondantes aux trois groupes par une analyse moléculaire. Notre étude a porté sur 26 souches du complexe C. parapsilosis, préalablement identifiées par les méthodes mycologiques classiques, isolées entre janvier 2011 et juin 2014 dans le laboratoire de parasitologie-mycologie de l’hôpital La Rabta. Parmi les 26 souches, 19 ont été isolées à partir d’hémocultures ; 3 à partir de prélèvements auriculaires ; 2 à partir de prélèvements buccaux et 2 au niveau de cathéters. Trois protocoles d’extraction d’ADN génomique du complexe C. parapsilosis ont été testés : un kit d’extraction (Quick Yeast Genomic DNA Extraction Kit), l’acétate de lithium et l’acétate de potassium. Puis, nous avons mis en place une technique de diagnostic moléculaire par PCR-RFLP. Le gène SADH (716 pb) a été choisi pour la présence au niveau de sa séquence d’un polymorphisme de restriction BanI. L’amplification du gène SADH permet, après digestion par l’enzyme de restriction BanI, d’isoler les trois groupes selon le profil obtenu. Les résultats obtenus au cours de ce travail ont montré que la méthode d’extraction utilisant l’acétate de lithium était la plus efficace en termes de rendement et de profil d’extraction. Le contrôle par électrophorèse de l’amplification du gène codant pour la SADH a confirmé l’identification phénotypique en mettant en évidence la bande de 750 pb spécifique du complexe C. parapsilosis. Enfin, le contrôle par électrophorèse des réactions de digestion enzymatique par BanI des amplifias du gène SADH a montré, pour les 26 souches testées, la présence de 2 bandes de 200 pb et de 550 pb, correspondant à l’espèce C. parapsilosis sensu stricto. Ces résultats doivent impérativement être confirmés par séquençage automatique des produits d’amplification par PCR du gène codant pour la SADH pour chaque souche isolée.

Allogeneic hematopoietic cell transplantation (HCT) activity significantly increased in the Eastern Mediterranean area over the past decade. However, comparative outcomes with longer established centers, especially European Blood and Marrow Transplantation (EBMT) centers, have not been reported. We compared outcomes of matched-sibling allogeneic HCT between East Mediterranean Blood and Marrow Transplantation (EMBMT) and EBMT centers for adult patients with AML in first CR using myeloablative conditioning. We matched 431 patients from EMBMT with 431 patients from EBMT centers according to patient, disease and transplant characteristics. EMBMT recipients and donors were more likely to be CMV seropositive. There were no significant differences in the incidence of acute or chronic GVHD, or the 3-year cumulative incidence of non-relapse mortality (NRM) and relapse incidence (RI) between the two groups (NRM: EMBMT=16% vs EBMT=11), (RI: EMBMT=13% vs EBMT=19%). Notably, the 3-year leukemia-free survival (LFS) and OS were similar between the groups (LFS: EMBMT=70±2% vs EBMT=69±3%), (OS: EMBMT=74±2% vs EBMT=73±2%). Despite differences in socioeconomics, health resources and transplant experience, matched-sibling allogeneic HCT outcomes in emerging centers in the EMBMT region appear similar to EBMT centers.

BM failure (BMF) is a major and frequent complication of dyskeratosis congenita (DKC). Allogeneic hematopoietic SCT (allo-HSCT) represents the only curative treatment for BMF associated with this condition. Transplant-related morbidity/mortality is common especially after myeloablative conditioning regimens. Herein, we report nine cases of patients with DKC who received an allo-SCT at five different member centers within the Eastern Mediterranean Blood and Marrow Transplantation Registry. Between October 1992 and February 2011, nine DKC patients (male, 7 and female, 2), with a median age at transplantation of 19.1 (4.9–31.1) years, underwent an allo-HSCT from HLA-matched, morphologically normal-related donors (100%). Preparative regimens varied according to different centers, but was reduced intensity conditioning (RIC) in eight patients. Graft source was unstimulated BM in five cases (56%) and G-CSF-mobilized PBSCs in four (44%) cases. The median stem cell dose was 6.79 (2.06–12.4) × 106 cells/kg body weight. GVHD prophylaxis consisted of CsA in all nine cases; MTX or mycophenolate mofetil were added in five (56%) and two (22%) cases, respectively. Anti-thymocyte globulin was administered at various doses and scheduled in four (44%) cases. Median time-to-neutrophil engraftment was 21 (17–27) days. In one case, late graft failure was noted at 10.4 months post allo-HSCT. Only one patient developed grade II acute GVHD (11%). Extensive chronic GVHD was reported in one case, whereas limited chronic GVHD occurred in another four cases. At a median follow-up of 61 (0.8–212) months, seven (78%) patients were still alive and transfusion independent. One patient died of metastatic gastric adenocarcinoma and graft failure was the cause of death in another patient. This study suggests that RIC preparative regimens are successful in inducing hematopoietic cell engraftment in patients with BMF from DKC. Owing to the limited sample size, the use of registry data and heterogeneity of preparative as well as GVHD prophylaxis regimens reported in this series, we are unable to recommend a particular regimen to be considered as the standard for patients with this disease.