BackgroundKnowledge concerning the clinical and biological presentation, as well as the outcome of treatment, of biphenotypic acute leukemia in children is limited. Design and MethodsThis retrospective review analyzes the clinical features and outcome of children with biphenotypic acute leukemia diagnosed and treated over an 8-year period. According to the EGIL scoring system 24 (3.7%) of 633 patients with acute leukemia were classified as having biphenotypic acute leukemia. The diagnostic work-up and results were reviewed specifically for this study in the light of the newly published WHO criteria for the diagnosis of leukemia of ambiguous lineage. Based on these criteria, 11 (1.7%) patients were categorized according to the new nomenclature as having mixed phenotype acute leukemia. The majority of the patients (58.3%) had a B-lymphoid/myeloid phenotype, followed by the T-lymphoid/myeloid phenotype. The most frequent chromosomal abnormality involved the 14q32 locus. Patients received therapy based on a treatment regimen for acute lymphocytic leukemia regimen, which included myeloid-effective agents. ResultsAt a median follow up of 4 years (range, 6 month -7 years) the overall survival rate was 75.7% and the event-free survival rate was 73.5%. The survival of those patients who underwent hematopoietic stem cell transplantation in first complete remission was not different from that of the patients who were treated with chemotherapy alone (overall survival: 70.1% versus 81.1%, respectively, p=0.39; event-free survival: 70.1% versus 76.2%, respectively, p=0.75). The outcome of the 11 patients who were retrospectively classified as having mixed phenotype acute leukemia according to the new WHO criteria was excellent, with no relapses or deaths occurring among these patients. ConclusionsAn acute lymphocytic leukemia type of induction therapy, using agents that are active against lymphoid and myeloid leukemias, appears to be more effective in achieving and maintaining complete remissions regardless of whether the patients are classified according to EGIL criteria or the new WHO criteria. Hematopoietic stem cell transplantation may not be necessary for all patients in first complete remission.Key words: biphenotypic acute leukemia, diagnosis, therapy, immunophenotyping, stem cell transplant.Citation: Al-Seraihy AS, Owaidah TM, Ayas M, El-Solh H, Al-Mahr M, Al-Ahmari A, and Belgaumi AF. Clinical characteristics and outcome of children with biphenotypic acute leukemia. Haematologica 2009; 94:1682-1690. doi:10.3324/haematol.2009

• Hematopoietic cell transplantation results in long-term survival.• Primary graft failure is very high and the predominant cause of death.We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. Thirty-four percent of transplants used grafts from HLA-matched siblings, 13% from HLA-mismatched relatives, 12% from HLA-matched, and 41% from HLA-mismatched unrelated donors. The median age at transplantation was 12 months. Busulfan and cyclophosphamide was the most common conditioning regimen. Long-term survival was higher after HLA-matched sibling compared to alternative donor transplantation. There were no differences in survival after HLAmismatched related, HLA-matched unrelated, or mismatched unrelated donor transplantation. The 5-and 10-year probabilities of survival were 62% and 62% after HLA-matched sibling and 42% and 39% after alternative donor transplantation (P 5 .01 and P 5 .002, respectively). Graft failure was the most common cause of death, accounting for 50% of deaths after HLA-matched sibling and 43% of deaths after alternative donor transplantation. The day-28 incidence of neutrophil recovery was 66% after HLA-matched sibling and 61% after alternative donor transplantation (P 5 .49). The median age of surviving patients is 7 years. Of evaluable surviving patients, 70% are visually impaired; 10% have impaired hearing and gross motor delay. Nevertheless, 65% reported performance scores of 90 or 100, and in 17%, a score of 80 at last contact. Most survivors >5 years are attending mainstream or specialized schools. Rates of veno-occlusive disease and interstitial pneumonitis were high at 20%. Though allogeneic transplantation results in long-term survival with acceptable social function, strategies to lower graft failure and hepatic and pulmonary toxicity are urgently needed. (Blood. 2015;126(2):270-276)

Purpose Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi anemia (FA). Data on outcomes in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome (MDS), or acute leukemia have not been separately analyzed. Patients and Methods We analyzed data on 113 patients with FA with cytogenetic abnormalities (n = 54), MDS (n = 45), or acute leukemia (n = 14) who were reported to the Center for International Blood and Marrow Transplant Research from 1985 to 2007. Results Neutrophil recovery occurred in 78% and 85% of patients at days 28 and 100, respectively. Day 100 cumulative incidences of acute graft-versus-host disease grades B to D and C to D were 26% (95% CI, 19% to 35%) and 12% (95% CI, 7% to 19%), respectively. Survival probabilities at 1, 3, and 5 years were 64% (95% CI, 55% to 73%), 58% (95% CI, 48% to 67%), and 55% (95% CI, 45% to 64%), respectively. In univariate analysis, younger age was associated with superior 5-year survival (≤ v > 14 years: 69% [95% CI, 57% to 80%] v 39% [95% CI, 26% to 53%], respectively; P = .001). In transplantations from HLA-matched related donors (n = 82), younger patients (≤ v > 14 years: 78% [95% CI, 64% to 90%] v 34% [95% CI, 20% to 50%], respectively; P < .001) and patients with cytogenetic abnormalities only versus MDS/acute leukemia (67% [95% CI, 52% to 81%] v 43% [95% CI, 27% to 59%], respectively; P = .03) had superior 5-year survival. Conclusion Our analysis indicates that long-term survival for patients with FA with cytogenetic abnormalities, MDS, or acute leukemia is achievable. Younger patients and recipients of HLA-matched related donor transplantations who have cytogenetic abnormalities only have the best survival.

The study revealed that combined immunodeficiencies are not uncommon and are the most frequent occurring diagnosis in our patient population. This study is a prerequisite to establish a national registry of primary immunodeficiency in Saudi Arabia.

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Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) is one of approximately 50 known lysosomal storage disorders. MPS VI is characterized by an absence or deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B) resulting in accumulation of dermatan sulfate. Prior to the availability of enzyme replacement therapy (ERT) the clinical management of MPS VI was limited to supportive care and allogeneic hematopoietic stem cell transplantation (HSCT); however, due to the rarity of this disease, little is known about the long-term outcomes of HSCT for MPS VI. The following retrospective study was performed using aggregate data gathered by the Center for International Blood and Marrow Transplant Research (CIBMTR) between 1982 and 2007 to determine survival probability for patients with MPS VI following allogeneic HSCT. This analysis identified 45 MPS VI patients with a median age of 5 years (range, 1-22 years) at the time they received an allogeneic HSCT. Cumulative incidence (95% CI) of acute graft vs. host disease at 100 days was 36% (21-53%). Probability of survival was 78% (65-89%) at 100 days and 66% (52-79%) at 1 and 3 years. While these data are based upon small numbers of recipients, they represent the largest series to date and may help clinicians assess the relative risks and benefits of currently available therapies.

Pulmonary complications after hematopoietic cell transplantation (HCT) can lead to significant morbidity and mortality. Limited evaluation of the true incidence of these complications in children and subsequent outcomes of these complications have not been evaluated recently. In April 2018, the National Heart, Lung, and Blood Institute; the Eunice Kennedy Shriver National Institute of Child Health and Human Development; and the National Cancer Institute cosponsored a meeting of experts to describe the status of pulmonary complications in children after HCT, identify critical gaps in knowledge, and explore avenues for research to advance care and optimize outcomes. The Center for International Blood and Marrow Transplant Research was used to evaluate the cumulative incidence of pulmonary complications in children and their respective survival. Of the 5022 children included in this analysis who received allogeneic HCT from 2010 to 2016, 606 developed pulmonary complications within the first year after HCT. Pneumonitis occurred in 388 patients, 125 patients developed pulmonary hemorrhage, and 200 patients had lung graft-versushost disease (GVHD). For those developing pulmonary complications within 1 year, overall survival 100 days after diagnosis of pulmonary complications was 49% (95% confidence interval [CI], 43% to 54%) for patients with pneumonitis, 23% (95% CI, 16% to 31%) in patients with pulmonary hemorrhage, and 87% (95% CI, 81% to 91%) in patients with pulmonary GVHD. This study demonstrates the approximate incidence of these complications, as well as their significant effects on survival, and can serve as a baseline for future research.

Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapybased conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.