First experience of the use of a generic of plerixafor in peripheral blood stem cell mobilization in multiple myeloma and lymphoma patients.

Mobilization failure in patients is a major therapeutic concern which makes subsequent ASCT impossible. A new growth factor called Plerixafor (Mozobil®) developed by the pharmaceutical industry (Sanofi-aventis, France), is a chemoreceptor antagonist, CXCR4 type, which disrupts the interaction of SDFI and CXCR4, thereby enhancing the effect of G-CSF mobilization and is especially indicated for mobilization failure. Currently, there is a generic of plerixafor developed by the pharmaceutical industry (Hetero Drugs Ltd, India). The brand name of this medicine is Mozifor®. The objective of this study was to evaluate if generic plerixafor has the same efficacy and safety as originator plerixafor when used with G-CSF in the mobilization of PBSCs for autologous ASCT in multiple myeloma (MM) and lymphoma failure patients. The 32 patients received plerixafor were divided in two groups. The first group concerns the 11 consecutive patients prospectively received generic plerixafor (Mozifor®) in the period between January to July 2020. These were compared with a retrospective control cohort (second group n = 21) who had been treated between 2009 and 2019 with originator plerixafor (Mozobil®). For the Mozifor® group, the mean CD34+ was 4.54x106/kg(1.56-6.79), the median time to achieve an absolute neutrophil count >0.5 G/L was 13 days (range: 8-21). The median time to self-sustained platelet count >20 G/L was 15 days (range: 8-24). For the Mozobil® group, the mean CD34+ was 3.1x106/kg (0.56-8.91) (p=0.86), the median time to achieve an absolute neutrophil count >0.5 G/L was 10 days (range 7-23). The median time to self-sustained platelet count >20 G/L was 13 days (range: 7-29). Our study showed that the generic of plerixafor was practically identical to that of the originator (Mozobil®) with no significant difference (p = 0.52). This study demonstrates the safety and feasibility of mobilization PBSC with generic plerixafor in ASCT in MM and lymphoma. Although these outcomes are encouraging, prospective comparison with other traditional auto-HCT regimens used for patients with MM and lymphoma is warranted.

A simplified method for autologous stem cell transplantation in multiple myeloma.

BACKGROUND AND OBJECTIVES: We evaluated the efficacy and safety of non-cryopreserved storage of autologous hematopoietic stem cells with no post-transplant granulocyte colony-stimulating factor (G-CSF) support in adult patients undergoing autologous stem cell transplantation (ASCT) for multiple myeloma (MM). DESIGN AND SETTING: Retrospective review of patients undergoing ASCT from May 2009 to July 2011. PATIENTS AND METHODS: Autologous stem cell were mobilized using G-CSF. Leukapheresis to harvest stem cells was performed on day -2 and -1. The grafts were kept in a conventional blood bank refrigerator at 4°C until reinfusion on day 0. The conditioning regimen consisted of melphalan 200 mg/m2 in all patients. The post-chemotherapy myeloablative phase was managed without growth factors. RESULTS: Between May 2009 to July 2011, 54 adults with MM were treated in our center in Oran. The median age at ASCT was 55 years (range, 35-65). There were 37 males and 17 females. The median harvested CD34+ cell count was 3.60X106/kg (range, 1.90 to 10.52). All patients had neutrophil engraftment on the median of day 10 (range, 6-17) and platelet transfusion independence on the median of day 13 (range 9-24). In the 47 evaluable patients the median post-transplant overall survival had not been reached; the estimated overall survival at 30 months was 93.8% (0.05%) , and the estimated disease-free survival at 27 months was 93.6% (0.05%). CONCLUSION: High-dose chemotherapy and ASCT using non-cryopreserved stem cells and no G-CSF support is safe and feasible in the treatment of MM under our work conditions in developing countries.

A population-based study of the epidemiology and clinical features of adults with acute myeloid leukemia in Algeria: report on behalf of the Algerian Acute Leukemia Study Group.

BACKGROUND AND OBJECTIVES: In Algeria, the incidence of hematologic malignancies has been difficult to estimate for many years. Today, many hematological centers, including 14 university hospitals, have been developed in the entire north and have useful epidemiological data pertinent to acute myeloid leukemia (AML). We studied the incidence of AML and its subtypes, age distribution, geographic distribution and trends in the rate of diagnosis over the last 5 years in Algeria. Secondary goals were to study trends of referral of AML cases from various regions to specific centers to assess the needs for health infrastructure and change of current practices. DESIGN AND SETTING: Retrospective analysis of nationwide survey of all adult cases of AML (>16 years) diagnosed between 1 January 2006 and 31 December 2010. PATIENTS AND METHODS: A survey form was distributed to all departments of hematology at the 15 participating centers. RESULTS: The 1426 cases of AML diagnosed during the study period represented an annual incidence of 0.91/100000 persons with a male to female (M/F) ratio of 1:16 and a median age of 45 years (range, 16-82 years). Nationally, 20% of cases AML were diagnosed in the whole western region of the country, 47% in the central and 33% in the east. There was a trend of continuous increase in the rate with age and in the rate of diagnosis over the last 5 years. The most common subtype was M2, followed by M4 and M5. CONCLUSION: An overall increase in the number of AML patients diagnosed nationwide over the last five years indicates a need for additional health care resources including curative and therapy-intense strategies, such as stem cell transplant facilities to optimize outcome. The relatively younger age of patients compared to the Western countries may be due to the demographic composition of our population.

The spectrum of beta-thalassemia mutations in the Oran region of Algeria.

In order to delineate the spectrum of beta-globin gene defects causing beta-thalassemia in the Oran region of Algeria, we have analyzed a representative sample of 31 beta-thalassemia patients. This led to the detection of 10 mutations. Four of them [nonsense codon 39 (C->T), IVS-I-110 (G->A), IVS-I-2 (T->C), and frameshift codon 6 (-A)] account for approximately 77% of the beta-thalassemia chromosomes. Three of these mutants are also widespread in Mediterranean populations, whereas the fourth, IVS-I-2 (T->C), appears typical of the Oranese population. The six other variants are less frequent. The possible origin of these mutated alleles, either by recurrent mutational event or by migration from other populations, is discussed.

Extent and high frequency of a short conversion between the human A gamma and G gamma fetal globin genes.

Southern blotting and DNA sequencing after polymerase chain reaction (PCR) amplification provide evidence for the frequent occurrence (in 7 out of 24 chromosomes) of a short conversion G gamma----A gamma in the 3' end of the human fetal A gamma globin gene. This short conversion is characterized by the presence, 3 nucleotides downstream from the termination codon of the A gamma gene, of the TCAC sequence that is normally present at the equivalent position at the 3' end of the G gamma gene; it is therefore identical to a conversion already described. Interestingly, we have found that this conversion is associated with the presence of the HindIII polymorphic restriction site in the A gamma IVS2, occupying an equivalent position in both the G gamma and A gamma genes. Our observations strengthen the hypothesis that the presence of the HindIII polymorphic restriction site in A gamma IVS2 and the presence of the sequence TCAC at the 3' end of the A gamma gene might be the result of a single conversion event.

Genetic factors involved in human G gamma and A gamma globin gene expression.

G gamma to A gamma globin ratios, haplotypes at the beta globin gene cluster and the C----T substitution at -158 5' to the G gamma globin gene were studied in three Algerian families that include SS or S-beta(0) thal patients. G gamma to A gamma ratios were found similar, within a family, in subjects displaying the same combination of chromosomes 11, the ratio observed for a given combination depending on the chromosome haplotypes. Our data can be explained by the existence of several alleles of a genetic factor closely linked to the beta globin gene cluster and involved in the determination of G gamma to A gamma globin ratio.

[Medical transfers in pediatric oncology. Reflections apropos of economic, technical and ethical problems (Oran 1977-1983)]. / Transferts sanitaires en oncologie pédiatrique. Réflexions à propos de problèmes économiques, techniques et éthiques (Oran 1977-1983).

In an underdeveloped country such as Algeria [20 million inhabitants, 2,140 US Dollars per capita gross national product (GNP)], satisfying a high level of health demand is difficult both in primary care and hospital. Limited facilities (hospital beds 2.3%; physicians 1:2,500; public health expenditure: 2% of GNP) combined with demographic pressure (population under 15 years of age: 47%) further compromise medical benefits. Qualitatively severe diseases such as pediatric cancers cannot be wholly managed locally. Thus administrative regulations permit sending patients with such situations abroad. We tested the feasibility of managing locally to a great extent (radiotherapy excepted) pediatric cancers. For leukemias and lymphomas, actuarial life expectancies corresponded to middle values of internationally published data. Cost-benefit estimations seemed good compared with other severe diseases managed both locally and abroad. Our present problem deals with balancing oncologic activity (more than 100 new cases a year) within a general pediatric department practice.

[Management of beta-thalassemias in a developing country. Experience of a pediatric service in Oran (Algeria)]. / Prise en charge des bêta-thalassémies dans un pays en voie de développement. Expérience d'un service de pédiatrie d'Oran (Algérie).

The management of beta-thalassemia in a developing country faces a host of organizational, logistic, and funding problems. Experience acquired against this background of multiple deficiencies is reported here. Only 60% of children with documented beta-thalassemia were monitored more or less regularly. The remaining 40% died or were lost to follow-up. Clinical results were acceptable in terms of growth but transfusion goals (pretransfusion Hb greater than or equal to 10 g/dl) were achieved in only 7% of cases and adverse effects to transfusions proved difficult to prevent. Lastly, funding remained grossly inadequate since only 5.4% of actual costs in drugs and small equipment were covered. This lack of funds has a major impact on decision-making concerning the care of this type of patient.

Structural characterization of the beta-globin gene cluster in an individual expressing a very low level of G gamma globin chains.

We report the case of a normal individual displaying an extremely unbalanced G gamma/A gamma-globin ratio (G gamma-globin chains undetectable by urea/triton/ acrylamide gel electrophoresis and just reaching the threshold of detection by high performance liquid chromatography) associated with a very low level of G gamma-globin mRNA (at the most 5% of total gamma-mRNA after reverse transcriptase polymerase chain reaction determination). By DNA Southern blotting and sequencing, the very low level of G gamma-globin chains in this individual was found in association with subhaplotype [+ -----] (Hinc II 5' to epsilon, Xmn I 5' to G gamma, Hind III in G gamma and A gamma, Hinc II in and 3' to psi beta), with G gamma- and A gamma-globin gene sequences of the B type chromosome, and with a number of AT repeats in the locus control region hypersensitive site-2 site, similar to that reported to be associated with the Bantu beta S haplotype. These structural characteristics, described for the first time combined in the same individual, suggest that the G gamma/A gamma ratio in adults, is controlled by sequences distributed all along the beta-globin gene cluster.

[Acute lymphoblastic leukemia in children. Evaluation of risk factors and results of treatment in a pediatric milieu]. / Leucémies aiguës lymphoblastiques de l'enfant. Estimation des facteurs de risque et résultats de prise en charge en milieu pédiatrique.

Rapid progress in acute lymphoblastic leukemia treatment in childhood has allowed five years survival rates at least for 50% vs 30% of standard risk (60-70%) and high risk (30-40%) patients. Analyzing our material from University Hospital Pediatric Department (Oran, Algeria) was leading to such conclusions as: First: excess of higher risk acute lymphoblastic leukemias; Second: excess of bad prognosis enzymatic/cytologic markers; Third: post therapeutic 5 years survival probability compares with lowest figures found in literature. Bearing in mind higher risk clinical material and poorer resources of hospital facilities, medical manpower and nursing in such an underdeveloped country as Algeria, therapeutic results seemed reasonably promising.

Origin and spread of beta-globin gene mutations in India, Africa, and Mediterranea: analysis of the 5' flanking and intragenic sequences of beta S and beta C genes.

Nucleotide polymorphisms of both the 5' flanking and intragenic regions of the human beta-globin gene were investigated by directly sequencing genomic DNA after amplification by the polymerase chain reaction in 47 subjects homozygous for the beta S or the beta C mutation. The sickle-cell mutation was found in the context of five different haplotypes defined by eight nucleotide substitutions and various structures of a region of the simple repeated sequence (AT) chi Ty. All subjects from the same geographic origin bear an identical chromosomal structure, defining the Senegal-, Bantu-, Benin-, Cameroon-, and Indian-type chromosomes. These results strengthen our previous conclusions about the multiple occurrence of the sickle-cell mutation. The Benin-type chromosome was also found among Algerian and Sicilian sickle-cell patients, whereas the Indian-type chromosome was observed in two geographically distant tribes, illustrating the spread of these sickle-cell genes. We also found that the intragenic sequence polymorphisms (frameworks) are not always in linkage disequilibrium with the BamH I polymorphism downstream from the beta-globin gene, as had been previously observed. Finally, we present a tentative phylogenetic tree of the different alleles at this locus. Some polymorphisms of this sequence might be contemporary with our last common ancestor, the great apes, that is, about 4-6 millions years old.

Anthropological approach to the heterogeneity of beta-thalassemia mutations in northern Africa.

Results of an epidemiological survey for beta-thalassemic defects involving 239 chromosomes in Algeria are analyzed in relation to the geographic and historical background of the country and are compared with published series for the Tunisian population. Four common mutations account for 81% of the chromosomes, but 13 other defects have been found, illustrating the highly heterogeneous nature of the disease in the northern African countries of the Maghreb. The high frequency of homozygous cases reflects the endogamous social structure of these populations. Distribution of the mutations and linkage to specific RFLP haplotypes provide information concerning their origin and date of introduction in good correlation with the anthropological history of Algeria.