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Sickle cell anemia (SCA) remains associated with high risks of morbidity and early death. Allogeneic hematopoietic SCT (HSCT) is the only curative treatment for SCA. We report our experience with transplantation in a group of patients with the non-Black African variant and the Black African variant of SCA. This study included 40 consecutive SCA patients (13 patients with the non-Black African variant and 27 with the Black African variant) who underwent BM transplantation from HLA-identical sibling donors between June 2004 and May 2013, following a myeloablative-conditioning regimen. All patients obtained sustained engraftment. One patient (non-Black African variant) became a stable mixed chimera with 25% donor cells more than 6 years after transplantation. The probabilities of survival, SCA-free survival and TRM at 5 years after transplant were 91%, 91% and 9%, respectively. All surviving patients remained free of any SCA-related events after transplantation. Our results confirm that it is possible to offer a greater than 90% chance of cure to children with SCA. HSCT should be considered the standard of care for who have an HLA-identical donor, before complications result from the sickling of RBC.

Ninety-seven patients affected by high-risk hematological malignancies underwent G-CSF primed, unmanipulated bone marrow (BM) transplantation from a related, haploidentical donor. All patients were prepared with an identical conditioning regimen including Thiotepa, Busilvex, Fludarabine (TBF) and antithymocyte globulin given at myeloablative (MAC=68) or reduced (reduced intensity conditioning (RIC)=29) dose intensity and received the same GvHD prophylaxis consisting of the combination of methotrexate, cyclosporine, mycofenolate-mofetil and basiliximab. Patients were transplanted in 1st or 2nd CR (early phase: n =60) or in >2nd CR or active disease (advanced phase: n =37). With a median time of 21 days (range 12–38 days), the cumulative incidence (CI) of neutrophil engraftment was 94±3%. The 100-day CI of III–IV grade acute GvHD and the 2-year CI of extensive chronic GvHD were 9±3% and 12±4%, respectively. Overall, at a median follow-up of 2.2 years (range 0.3–5.6), 44 out of 97 (45%) patients are alive in CR. The 5-year probability of overall survival (OS) and disease-free survival (DFS) for patients in early and advanced phase was 53±7 vs 24±8% ( P =0.006) and 48±7 vs 22±8% ( P =0.01), respectively. By comparing MAC with RIC patient groups, the transplant-related mortality was equivalent (36±6 vs 28±9%) while the relapse risk was lower for the MAC patients (22±6 vs 45±11%), who showed higher OS (48±7 vs 29±10%) and DFS (43±7 vs 26±10%). However, all these differences did not reach a statistical significance. In multivariate analysis, diagnosis and recipient age were significant factors for OS and DFS. In conclusion, this analysis confirms, on a longer follow-up and higher number of patients, our previous encouraging results obtained by using MAC and RIC TBF regimen as conditioning for G-CSF primed, unmanipulated BM transplantation from related, haploidentical donor in patients with high-risk hematological malignancies, lacking an HLA-identical sibling or unrelated donor and in need to be urgently transplanted.

Background Advances in knowledge about the metabolic pathways involved in the pathogenesis of psoriasis and related diseases have led to a search for new therapeutic targets and the development of new biological drugs. Several studies have focused on HLA-C*06 and investigated correlations between the genetic risk factors of psoriasis and clinical parameters such as the severity of the disease and the response to treatment. Objective Our objective is to share experience from our institution in the observation of two patients with severe chronic plaque psoriasis who were unresponsive to any anti-TNF-α treatment and only partially responsive to ustekinumab. The patients are carriers of a rare allele of HLA-C that occurs in Caucasians. Methods The patients with moderate-to-severe chronic plaque psoriasis, and candidates for biological therapy were typed for the HLA-C locus at high resolution via polymerase chain reaction sequence-specific oligonucleotide probes (PCR-SSOP) using a commercial kit (LAB ® Type, One Lambda Inc., Canoga Park, CA, USA). The socio-demographic variables and clinical data were collected. Results In our cohort of 134 patients, only two showed the presence of the allele HLA-C*18:01. To our knowledge, a coincidence between HLA-C*18 and severe psoriasis in Caucasian patients has not previously been described. The fact that both of these patients showed the same clinical history (unresponsive to any anti-TNF-α treatment and partially responsive to ustekinumab) cannot be attributed to a random observation because HLA-C*18 is extremely rare in Europe. As a consequence, at this latitude, it probably indicates a severe disease for which the proper therapy has still not been identified.

We analyzed the long-term outcome of 4865 patients treated in Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia (ALL) of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Treatment was characterized by progressive intensification of systemic therapy and reduction of cranial radiotherapy. A progressive improvement of results with reduction of isolated central nervous system relapse rate was obtained. Ten-year event-free survival increased from 53% in Study 82 to 72% in Study 95, whereas survival improved from 64 to 82%. Since 1991, all patients were treated according to Berlin-Frankfurt-Muenster (BFM) ALL treatment strategy. In Study 91, reduced treatment intensity (25%) yielded inferior results, but intensification of maintenance with high-dose (HD)- L -asparaginase (randomized) allowed to compensate for this disadvantage; in high-risk patients (HR, 15%), substitution of intensive polychemotherapy blocks for conventional BFM backbone failed to improve results. A marked improvement of results was obtained in HR patients when conventional BFM therapy was intensified with three polychemotherapy blocks and double delayed intensification (Study 95). The introduction of minimal residual disease monitoring and evaluation of common randomized questions by AIEOP and BFM groups in the protocol AIEOP-BFM-ALL 2000 are expected to further ameliorate treatment of children with ALL.

Since 1982, four consecutive studies on childhood acute myeloid leukaemia (AML) (namely LAM-82, -87, -87M and -92) have been conducted in Italy by the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) group. The induction therapy of the first three studies consisted of daunorubicin and cytarabine structured in a 3+7 backbone. In the most recent protocol (LAM92), patients received two induction courses including idarubicin, cytarabine and etoposide. Patients with acute promyelocytic leukaemia (20% of diagnoses) were included in LAM-87 and 87M studies. Postremissional therapy significantly changed over time, with an ever-increasing role given to stem cell transplantation (SCT). The long-term outcome of patients enrolled in the LAM-82, 87 and 87M studies was comparable, whereas that of children treated according to LAM-92 study was significantly better ( P <0.005). Either allogeneic or autologous SCT was employed as consolidation therapy in more than 75% of cases enrolled in this latter study. Patients enrolled in the LAM-92 study were stratified in standard and high-risk groups with different outcome (67 vs 47%, respectively, P =0.04). Altogether, the results obtained in these four studies have permitted a progressive refinement of treatment, contributing to the structure of the ongoing LAM-2002 protocol that stratifies patients according to the presence of definite genetic anomalies and response to induction therapy.

Five-year event-free survival in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) currently exceeds 80–85%. However, 15–20% of patients still experience a relapsed/refractory disease. From 1 January 2015 to 31 December 2020, thirty-nine patients, 0–21 years old with r/r BCP-ALL were treated with blinatumomab with the aim of inducing remission (n = 13) or reducing MRD levels (n = 26) in the frame of different multiagent chemotherapy schedules, in seven AIEOP centers. Patients were treated in compassionate and/or off-label settings and were not enrolled in any controlled clinical trials. Treatment was well tolerated; 22 (56.4%) patients reported adverse events (AE) on a total of 46 events registered, of which 27 (58.7%) were ≤2 grade according to CTCAE. Neurological AEs were 18 (39.1%); only two patients required transient blinatumomab discontinuation. Complete remission (CR) rate was 46% for the 13 patients treated with ≥5% blasts and 81% PCR/FC MRD negativity in the 26 patients with blasts < 5%. Median relapse-free survival was 33.4 months (95% CI; 7.5–59.3); median overall survival was not reached over a mean follow-up of 16 months. In our study, as in other real-life experiences, blinatumomab proved to be effective and well-tolerated, able to induce a high rate of CR and MRD negativity.

We evaluated the incidence of GVHD, risk factors and the impact of graft composition on acute GVHD (aGVHD) in 92 children who underwent BMT for thalassemia following busulfan/cyclophosphamide (BUCY)-based conditioning regimens and GVHD prophylaxis with CSA/short-MTX and methylprednisolone. The incidence of grade 2–4 and 3–4 aGVHD was 35% (95% confidence interval (CI) 25–44) and 9% (95% CI 4–16), respectively. We found that CD3 + and CD34 + cell doses above the median were associated with high incidence of grade 2–4 aGVHD (49 vs 20%, P =0.005 and 46 vs 23%, P =0.021, respectively). In multivariate analysis, high CD3 + (hazard ratio (HR) 4.6; 95% CI 1.4–14.7; P =0.010) and CD34 + (HR 4.3; 95% CI 1.4–12.7; P =0.011) cell doses were associated with grade 2–4 aGVHD. We further examined the effect of CD3 + and CD34 + cell doses on aGVHD using quartile cutoff points and found a minimum threshold for CD3 + (38 × 10 6 /kg) and CD34 + (4 × 10 6 /kg) cells above which the incidence of grade 2–4 aGVHD is significantly increased. This study shows for the first time a positive correlation between the number of CD3 + and CD34 + cells and aGVHD in children receiving sibling BMT, and indicates that using tailored and more intensive post transplant immunosuppression may permit to better control aGVHD.

The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic SCT (allo-HSCT). We applied whole-genome analysis to investigate genetic variants—other than HLA class I and II—associated with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110 β-Thalassemic patients. We identified two single-nucleotide polymorphisms (SNPs) in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558, both located in the HLA class III region, in strong linkage disequilibrium between each other ( R 2 =0.92). When considered as single SNP, none of them reached a significant association with graft rejection (nominal P <0.00001 for BAT2 SNP rs11538264, and P <0.0001 for BAT3 SNP rs10484558), whereas the BAT2/BAT3 A/C haplotype was present at significantly higher frequency in patients who rejected as compared to those with functional graft (30.0% vs 2.6%, nominal P =1.15 × 10 −8 ; and adjusted P =0.0071). The BAT2/BAT3 polymorphisms and specifically the A/C haplotype may represent a novel immunogenetic factor associated with graft rejection in patients undergoing allo-HSCT.