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The first meeting of the African Blood and Marrow Transplantation (AfBMT) was held in Casablanca from April 19, 2018 to April 21, 2018, with the aim of fostering hematopoietic stem cell transplantation (HSCT) activity in Africa. Out of the 54 African countries, HSCT is available only in six (Algeria, Egypt, Morocco, Nigeria, South Africa, and Tunisia). During this meeting, African teams and international experts from the Worldwide Network for Blood and Marrow Transplantation (WBMT) gathered to share their experience and discussed ways to help fill the gap. Nurses and patients held their meeting in parallel. International support and collaboration can help by providing expertise adapted to local resources and regional population needs. Local engagement including government and private participants are necessary to initiate and develop local HSCT capability.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits is a new disorder with undefined treatment modalities. We propose cyclophosphamide‐bortezomib‐dexamethasone and autologous stem cell transplantation as a therapeutic protocol.

The purpose of our study was to investigate the epidemiology of coagulase negative staphylococci (CoNS) responsible for bacteremia in hematopoietic stem cell transplant (HSCT) recipients and to determine the prevalence and the genetic background of methicillin resistance. The prevalence of CoNS bacteremia was 7.4% (54/728), higher in allograft (10.7%) than in autograft (4.7%) recipients. A sepsis or a septic shock were observed in 9% of cases. No deaths were attributable to CoNS bacteremia. The methicillin resistance rate was 81%. All MR-CoNS, harbored mecA gene and 90% were typeable with SCCmec typing using PCR amplification. The SCCmec type IV was the most frequent (44%). Clonal dissemination of MR- Staphylococcus epidermidis strains was limited. Our study showed a low prevalence and favorable outcome of CoNS bacteremia in HSCT recipients with limited clonal diffusion. However, they were associated with a significant rate of severe infections and a high rate of methicillin resistance, mediated by SCCmec IV element in most cases.

Aim The objective of the study was to estimate the cumulative incidence (CI) of relapse, relapse-free survival (RFS) and overall survival (OS) in ALL patients after a once-a-day fractionated TBI (F-TBI) regimen with 9.9 Gy. The secondary objectives were evaluation of short and long-term toxicity and non-relapse mortality (NRM). Background Total body irradiation (TBI), as a part of the conditioning regimen before allogeneic stem cell transplantation (ASCT) for acute lymphoblastic leukemia (ALL), allows disease control by eradicating residual blast cells in the transplant recipient. Materials and methods Retrospective study conducted in patients with ALL who received between March 2003 and December 2013 a conditioning regimen with F-TBI and chemotherapy. Irradiation was delivered with 3.3 Gy once-a-day for three consecutive days. Results Eighty-seven patients were included. The median age was 19 years (range: 5–49 years). The 3-year CI of relapse was 30%. The estimated 3-year RFS and OS were 54% and 58%, respectively. Cumulative incidence of acute graft-versus-host disease (aGVHD) grade II–IV and chronic GVHD (cGVHD) was 31% and 40%, respectively. Interstitial pneumonitis was observed in 2 patients. The 3-year CI of NRM was 16%. In multivariate analysis, cGVHD was associated with a lower CI of relapse (RR = 0.26, 95% CI: 0.07–0.95, p = 0.04). High-risk cytogenetics was associated with a lower RFS (RR = 2, 95 CI: 1.04–3.84, p = 0.03). Grade II-IV aGVHD was an independent predictor of higher CI of NRM (RR = 6.7, 95% CI: 1.4–31.7, p = 0.02). Conclusions Once-a-day F-TBI regimen is effective, safe and practical in patients who underwent ASCT for ALL.

Human recombinant granulocyte colony stimulating factor reduces the duration of neutropenia following HLA-identical allogeneic bone marrow transplantation. However, its use remains controversial due to the risk of increasing the incidence of acute graft-versus-host disease (GVHD) and slower platelet recovery. To clarify these risks, we conducted a prospective randomized placebo-controlled trial of filgrastim 5 µg/kg/day i.v. from day 7 post-transplant until neutrophil recovery in 145 consecutive adults undergoing HLA-identical allogeneic bone marrow transplantation, with cyclosporine and methotrexate as GVHD prophylaxis. The primary endpoint was the incidence of acute GVHD; hematological recovery, nonrelapse mortality, and post-transplant complications were secondary endpoints. Filgrastim had no significant effect on the incidence of acute GVHD, platelet recovery, platelet transfusion requirements, chronic GVHD, or survival. Filgrastim accelerated granulocyte recovery significantly (with absolute neutrophil counts >.5 × 109/L achieved after a median of 16 days versus 23 days for placebo; P

Hematopoietic Stem Cell Transplantation (HSCT) activity was evaluated in the African (AFR)/EMRO region and compared to the global activity for the years 2006-2013. Data were obtained from 1570 teams in the 6 WHO continental regions. Of these, 29 (1.85%) of all teams were active in 12 of the 68 AFR/EMRO countries. They reported 2.331 (3.3%) of the worldwide 71.036 HSCT, and a transplant rate of 32.8 (TR; HSCT/10 million inhabitants; worldwide 128.5). This reflects still the lowest regional TR despite an increase of 90% since 2006. HSCT activity in AFR/EMRO countries was characterized by a higher use of allogeneic compared to autologous HSCT, an almost exclusive use of family donors, including haploidentical family donors. These findings contrast with the prevalence of autologous over allogeneic HSCT, and a higher frequency of unrelated HSCT in other parts of the world. Of note, the increase by 200% in HSCT for hemoglobinopathies from 2006 to 2013 (72 per year) in the AFR/EMRO region. This reflects the specific role of HSCT for these disease categories with high prevalence and incidence in the AFR/EMRO region. This report provides information for the competent authorities to foster adequate infrastructure. It urges transplant organization to optimize their cooperation.

Hematopoietic Stem Cell Transplantation (HSCT) is the only potentially curative treatment option for the hematologic complications that occur in patients with Fanconi anemia (FA). In this study, we present a retrospective multicenter analysis from the Eastern Mediterranean Blood and Marrow Transplantation Group (EMBMT) of matched related donor HSCT for FA in adolescents and adults transplanted between 1988 and 2015. Forty-five patients received HSCT with a median age at transplant of 18 years, the interquartile range (IQR) (15–23.5); 25 (55.6%) patients were females and 20 (44.4%) were males. Conditioning regimen was fludarabine-based in 29 (64.4%) patients, irradiation-based in five (11.1%) patients, and the remaining patients received other combinations. Indication for HSCT was bone marrow failure in 39 (86.7%) and myelodysplastic syndrome in six (13.3%) patients. Stem cell source was bone marrow in 22 (48.9%), peripheral blood in 20 (44.4%), umbilical cord blood in one (2.2%), and combination of bone marrow and cord blood in two (4.4%) patients. Twenty-seven (60%) patients engrafted and five (11.1%) had primary engraftment failure. The median time to neutrophil engraftment was 14 days (range 10–21 days); median time for platelet engraftment was 17 days (10–33 days). The probability of developing grade II–IV acute GVHD for all patients was 7.0% and chronic GVHD 36.6%. No new malignancies were reported. The OS probability was 53.6% (95% CI, 38.3–68.9%) with a median follow-up of 13 months (95% CI, 1–240). Our HLA-matched related HSCT results in AYA patients with FA compare favorably with other reported international registry data.

Resume Introduction L’anemie de Fanconi (AF) est une maladie hereditaire caracterisee par une heterogeneite genetique et phenotypique. De nombreux groupes ont mis en place des registres propres a leur pays. En Tunisie, le groupe tunisien d’etude de l’AF (GETAF) a cree le registre tunisien de l’AF « TFAR ». Patients et methodes Tous les services d’hematologie et de pediatrie de Tunisie ont ete contactes pour inclure leurs malades diagnostiques entre janvier 1983 et decembre 2008. Le registre TFAR a ete integre dans le site web du groupe GETAF a l’adresse : www.fanconi-tunisie.net . Resultats Le tri des fiches a permis de retenir 142 patients appartenant a 118 familles. L’âge median de diagnostic etait de 11 ans. Une consanguinite etait notee dans 86 % des cas, un syndrome malformatif dans 91 %, une pancytopenie au moment du diagnostic dans 69 %. Parmi 28 patients, 95 % appartenaient au groupe FANCA. Cent neuf patients etaient traites par androgenes et 27 avaient eu une allogreffe de moelle osseuse geno-identique. Un syndrome myelodysplasique (SMD) avait ete diagnostique dans 4 % des cas, une leucemie aigue (LA) dans 6 % et une tumeur solide dans 2 % des cas. L’âge median de survie etait de 17 ans et 5 mois, il etait significativement meilleur chez les patients allogreffes. Conclusion L’AF parait frequente en Tunisie. L’atteinte hematologique est la circonstance de decouverte la plus frequente. Elle est souvent moderee ou severe et necessite un traitement par androgenes ou allogreffe de moelle osseuse. Celle-ci devrait concerner tous les patients ayant un donneur familial HLA-compatible.

FY antigens are candidate minor histocompatibility antigens relevant to renal allograft rejection, but no data have been reported about their role in graft-versus-host disease (GVHD) incidence after human leukocyte antigen (HLA)-identical siblings hematopoietic stem cell transplantation (HSCT). The aim of this study was to examine the effect of donor/recipient disparity at FY antigens on the incidence of GVHD in Tunisian patients receiving an HLA-identical HSCT. This work enrolled 105 Tunisian pairs of recipients and their HLA-identical sibling donors of HSCs. FY genotyping was performed with the polymerase chain reaction-sequence-specific primer method and donor/recipient disparity for these antigens was analyzed at two levels: incompatibility and nonidentity. The case-control analyses showed no significant correlation between FY disparity and the incidence of either acute or chronic GVHD. Sample size calculation showed that 572 cases and 1716 controls would be necessary to be able to detect a significant association with 80% power and two-sided type I error level of 5% (α=0.05). The lack of association in the studied cohort may be explained by the low immunogenicity of FY antigens in HSCT context, compared with other antigens such as HA-1 and CD31.

Chemokine receptors are very important players in the pathogenesis of GVHD. The aim of this study is to test the hypothesis that the lack of expression of the DARC receptor on erythrocytes can affect the GVHD incidence. A total of 105 recipients and their 105 respective sibling donors of HSCs were enrolled in this study. All patients were evaluated for acute and chronic GVHD. The DARC genotyping assay was performed using the SSP-PCR method. The case–control analyses showed that the donor DARC 146G allele and T− 46G146 haplotype, coding for the FY2 version of DARC, are very significant in the GVHD paradigm because they are associated with the incidence of acute effects of this outcome in recipients (p = 0.007, χ² = 7.200). It seems that this version of DARC receptor is a powerful facilitator of chemokine transcytosis and subsequently leukocyte migration into GVHD target organs.

The CTLA-4 genetic variation, such as single nucleotide polymorphisms (SNPs) may be critical and can affect the functional activity of cells that initiate the graft-versus-host disease (GVHD) effects. The aim of this study is to examine the effect of donor CTLA-4 alleles and haplotypes for the -318C>T and the 49A>G polymorphisms on the occurrence of GVHD in Tunisians recipients of HSCs. A total of 112 patients and their 112 respective sibling donors of HSCs were enrolled in this study. All patients had either grades 0-I or grades II-IV acute GVHD, or chronic GVHD. The SNPs genotyping assay was performed using sets of sequence specific primers (SSP-PCR). The single marker association analysis showed that the 49G allele, in a genetic recessive model, may be a potential risk factor only for the chronic GVHD (p = 0.032, odds ratio [OR] = 2.58, 95% confidence interval = 1.05-6.32). The haplotypes analyses showed that the CTLA-4 -318C49G nucleotide combination is significantly associated with the incidence of chronic GVHD (p = 0.043, χ² = 3.27). Donor CTLA-4 -318C49G haplotype may be a significant risk factor for developing chronic GVHD after allo-stem cell transplantation. We suppose that donor T cells expressing this haplotype in a homozygous state have higher proliferation than those expressing other haplotypes, especially after recognition of the recipient's minor histocompatibility antigens.

Graft-versus-Host disease (GVHD) has been widely linked to immunogenetic causes such as disparity between the recipient and its HLA geno-identical donor for some Non-HLA antigens called minor histocompatibility antigens (MiHAgs). HA-2 is one of potential human MiHAgs but its effect on the GVHD occurrence remains not clear. In order to examine such association in the Tunisian cohort of HSCs recipients, we performed a retrospective study on patients who received an HLA-identical HSCT between 2000 and 2009. The study was performed on 60 HLA-A2-positive patients who had received a haematopoietic stem cell transplant from an HLA-identical sibling. All patients received cyclosporine A and/or methotrexate for GVHD prophylaxis. HA-2 genotyping assay was performed with SSP-PCR method and HLA-A*0201 positive samples were identified mainly with Luminex HLA-Typing method. Luminex HLA-Typing assay showed that only 53 cases were positives for the HLA-A*0201 allele. Among these cases, only 3 pairs were mismatched for the MiHAg HA-2. Acute GVHD occurred in 01 HA-2-mismatched pair while chronic GVHD was detected in 02 disparate couples. Univariate and multivariate analyses showed that MiHAg HA-2 disparity does not have any significant effect on the occurrence of either acute or chronic GVHD. This last one appeared to be correlated only with the age of patient (adulthood) (p: 0.011, OR: 22.092). Our findings support the previously reported data denying the influence of the HA-2 disparity on the GVHD occurrence after HSCT.

INTRODUCTION: Minor histocompatibility antigen HA-1 (MiHAg-HA-1) disparity between a patient and his or her human leukocyte antigen (HLA) genoidentical donor has been widely associated with an increased risk of graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. OBJECTIVE: To examine the effect of HA-1 disparity on the incidence of both acute and chronic graft-versus-host disease in Tunisian recipients of hematopoietic stem cells. METHODS: A total of 60 patients and their 60 respective sibling hematopoietic stem cell donors were enrolled in this study. All patients prophylactically received cyclosporine A and/or methotrexate for graft-versus-host disease. An HA-1 genotyping assay was performed with the SSP-PCR method, and HLA-A*0201- and/or HLA-A*0206-positive samples were identified using the Luminex HLA typing method. RESULTS: The Luminex HLA typing assay showed that 54 patients were positive for either the HLA-A*0201 or HLA-A*0206 alleles. Among these cases, six pairs were mismatched for MiHAg-HA-1. Both acute and chronic graft-versus-host disease occurred in four mismatched patients (Fisher's p-values were 0.044 and 0.170, respectively). A univariate logistic regression model analysis showed that only acute graft-versus-host disease may be affected by recipient MiHAg-HA-1 disparity (p: 0.041, OR: 6.727), while chronic graft-versus-host disease correlates with both age and recipient/donor sex mismatch (p: 0.014, OR: 8.556 and p: 0.033, OR: 8.664, respectively). CONCLUSION: Our findings support previously reported data suggesting a significant association between HA-1 disparity and the risk of acute graft-versus-host disease following hematopoietic stem cell transplantation.

Seventeen patients with Fanconi anemia (FA) underwent allogeneic bone marrow transplantation (BMT) from matched related donors (MRD) between January 1999 and June 2003. Median age at BMT was 11 years. Conditioning regimen consisted of low-dose cyclophosphamide (CY; 40 mg/kg) and busulfan (BU; 6 mg/kg) with the addition of lymphoglobulin (20 mg/kg) in two patients. Graft-versus-host disease (GVHD) prophylaxis included cyclosporine A (CsA) and methotrexate (MTX; 5 mg/m(2) at day 1, 3, 6). All patients engrafted (for an absolute neutrophil count >0.5 x 10(9)/L) after a median time of 12 days (range 10-16 days). Fourteen patients (82%) had sustained grafts, whereas three others (18%) rejected grafts between day +39 and +80 after transplantation. Two of them are still alive after successful second PBSC transplantation and one died. Acute and chronic GVHD occurred in 23% and 13% of patients, respectively. With a median follow-up of 16 months (range 3-53 months), survival rate was 72% and Karnofsky score was at least 90%. The low-dose BU/CY regimen, in FA patients allografted from an HLA-matched related donor, allowed engraftment with relative low toxicity. Early graft failure (GF) remains a problem and may require modification of this regimen.

Neisseria mucosa, a Gram-negative diplococcus, is part of normal nasopharyngeal flora. We report a case of bacteremia caused by N. mucosa in a 50-year-old neutropenic patient suffering from non-secretory multiple myeloma stage IIIA. This case underscores that mostly nonpathogenic N. mucosa can cause bacteremia in neutropenic patients who developed mucositis after hematopoietic stem cell transplantation.

International audience; Tunisian population is characterized by its heterogeneous ethnic background and high rate of consanguinity. In consequence, there is an increase in the frequency of recessive genetic disorders including Fanconi anemia (FA). The aim of this study was to confirm the existence of a founder haplotype among FA Tunisian patients and to identify the associated mutation in order to develop a simple tool for FA diagnosis. Seventy-four unrelated families with a total of 95 FA patients were investigated. All available family members were genotyped with four microsatellite markers flanking FANCA gene. Haplotype analysis and homozygosity mapping assigned 83 patients belonging to 62 families to the FA-A group. A common haplotype was shared by 42 patients from 26 families at a homozygous state while five patients from five families were heterozygous. Among them, 85% were from southern Tunisia suggesting a founder effect. Using multiplex ligation-dependent probe amplification (MLPA) technique, we have also demonstrated that this haplotype is associated with a total deletion of exon 15 in FANCA gene. Identification of a founder mutation allowed genetic counseling in relatives of these families, better bone marrow graft donor selection and prenatal diagnosis. This mutation should be investigated in priority for patients originating from North Africa and Middle East.

Interleukine 6 (IL-6) is the most important cytokine involved in malignant plasma cells growth and survival.To analyse bone marrow plasma cells IL6 receptor gene expression in both multiple myeloma patients at diagnosis and healthy bone marrow donors.Clinical and biological patients' features and responses to Dexamethasone-Thalidomide induction therapy were gathered. 47 patients and 16 case controls were analyzed: Bone marrow plasma cells were isolated; and IL6 receptor gene expression was quantified using Taqman quantitative PCr technology and 2-ΔCT formula.Quantitative and qualitative IL6 receptor gene expression were negatively correlated with the degree of response to therapy (p= 0.02). In this study, plasma cells IL6 receptor gene expression seems to be decisive in predicting the response to treatment.Understanding the mechanisms involved in plasma cells IL6 receptor gene expression may offer a better appreciation of the physiopathologic and anti-oncogenic ways of drug resistance in multiple myeloma and consequently the discovery of new specific drugs.

International audience; Background:Chromosome breakage hypersensitivity to alkylating agents is the gold standard test for Fanconi anemia (FA) diagnosis. The aim of the present study was to assess the proportion of FA cases among aplastic anemia (AA) in Tunisian pediatric patients.Observation:Investigation of mitomycin C-induced chromosomal breakage was carried out in 163 pediatric patients with AA and siblings of the cases where diagnosis of FA was confirmed. We identified 31 patients with FA whose percentage of unstable mitoses ranges from 65% to 100%. Among 18 siblings who were investigated for chromosomal instability, 3 were incidentally found to be affected.Conclusions:FA is an important cause of AA in Tunisia. Our report is the first study in North Africa that explored cytogenetic and phenotypic findings in FA children. It also showed the importance of mitomycin C sensitivity screening in all FA siblings.

Objective The aim of this study is to examine the effect of donor PECAM-1 alleles and haplotypes for the SNPs L98V, S536N, and R643G on the occurrence of GVHD in Tunisian recipients of HSCs. Design and methods This study enrolled 102 patients and their 102 respective HLA-identical sibling donors of HSCs. The PECAM-1 SNPs genotyping assay was performed using sets of sequence specific primers (SSP-PCR). Results The single marker association analysis showed that the L98 allele, in a recessive genetic model, may be a potential risk factor only for acute GVHD ( p = 0.036, OR = 2.580, 95% C.I. = 1.053–6.326). However, the haplotype analysis showed a lack of association between donor's PECAM-1 SNPs and GVHD incidence in recipient. Conclusion The homozygosity state for donor PECAM-1 L98 allele may be a significant risk factor for acute GVHD. This is probably due to its action on the function of donor leukocytes especially during the extravasation process.

GVHD is the major cause of mortality after HLA-identical HSCT. Such complication has been widely linked to donor/recipient disparity for minor histocompatibility antigens (MiHAgs). PECAM-1 is one of potential human MiHAgs but its effect on the GVHD occurrence remains not clear. In order to examine such association in the Tunisian cohort of HSCs recipients, we performed a retrospective study on patients who undergone HLA-identical HSCT between 2000 and 2009. Genotyping of the three selected PECAM-1 polymorphisms (rs668, rs12953 and rs1131012) was performed with SSP-PCR method. Univariate analyses showed that grades II–IV acute GVHD were considerably linked to the non-identity for rs12953 only in HLA-B44-like positive patients ( p = 0.010, OR = 10.000). Multivariate analysis for chronic GVHD showed that this outcome may be affected only by the adulthood and the conditioning regimen. Our findings support the previously reported data suggesting a significant association between the PECAM-1 disparity and the risk of acute GVHD.

In 1998, the Tunisian team of the ‘Centre National de Greffe de Moelle Osseuse’ initiated allogeneic hematopoietic SCT (AHSCT) in Tunisia. As of June 2007, information was collected about 299 patients with a first AHSCT and 12 additional retransplants. The median age was 19 years (range 2–49 years). The main indications were aplastic anemia (n=106, 36%), leukemia and nonmalignant disorders (n=153, 51%), Fanconi anemia (n=26, 9%) and other nonmalignant disorders (n=14, 4%). Preparative regimens depended on indication. All donors were HLA geno-identical. The stem cell sources were BM (87%) and PBSCs (13%). At the time of analysis, 200 patients (67%) were alive after a median follow-up of 42 months (range 3–112 months). The overall TRM rate was 17%. Outcome depended on indication. According to our results, allogeneic HSCT is potentially curative for hematological diseases, but it is a toxic approach for malignant disorders.

A 55-year-old man with multiple myeloma developed sustained bleeding after bone marrow aspiration and cutaneous bleeding. Routine coagulation studies revealed a prolonged activated partial thromboplastin time and thrombin time (> 60 s) with a normal reptilase time. Further evaluation showed failure of the activated partial thromboplastin time to correct completely in a 1: 1 mixture with normal plasma. Treatment of the patient's plasma in vitro with protamine sulfate normalized the thrombin time. The presence of a heparin-like anticoagulant was suspected. The plasma heparin level was 0.73 IU/ml. Intravenous infusion of protamine sulfate appeared to neutralize the anticoagulant activity and stop the bleeding. The cancer cells themselves or the invasive nature of this type of cancer might result in a massive release of a heparinoid. Such coagulopathy appears to be a rare mechanism of bleeding and it is an important entity to consider since it is potentially reversible with protamine sulfate.