Impact of ABO-incompatible donor on early and late outcome of hematopoietic stem cell transplantation.

ABO incompatibility is not a barrier to allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of an ABO mismatch on the outcome of the HSCT remains controversial. We analyzed whether ABO incompatibility leads to an increased risk of early/late complications, mortality, or increased transfusion requirements. The 147 consecutive allogeneic HSCTs includes 80 ABO-identical and 25 major, 30 minor, and 12 bidirectional ABO-mismatched grafts. The four groups were balanced with respect to disease status at transplantation. Transplantation-related mortality was significantly greater (P < .01) and overall survival significantly shorter (P = 0.2) among HSCT recipients with minor ABO-mismatched grafts. The relapse rate, progression-free survival, and transfusion requirements until discharge were not different between ABO-identical and ABO-mismatched groups. Pure red cell aplasia (PRCA); (P < .0001) and delayed red blood cell (RBC) engraftment (P < .001) were more frequent in HSCT recipients with major mismatched donors. Delayed RBC engraftment was associated with posttransplantation hyperferritininemia and increased mortality risk (P = .05). The greater frequency of sinusoidal obstruction syndrome and graft-versus-host disease (GVHD) in patients with minor mismatched transplants, did not show statistical significance. In contrast severe GVHD was significantly more frequent among minor mismatched patients (P = .04). ABO-mismatched HSCT might have an unfavorable impact on transplant outcomes. Selection of ABO-compatible donors when possible, strategies to prevent and treat PRCA, modifications in transfusion practice, and effective iron chelation are among the measures that can improve transplant outcomes.

Benefit of high-dose methylprednisolone in comparison with conventional-dose prednisolone during remission induction therapy in childhood acute lymphoblastic leukemia for long-term follow-up.

Eight-year event-free survival (EFS) was evaluated in 205 patients with acute lymphoblastic leukemia (ALL), to consider the efficacy of high-dose methylprednisolone (HDMP) given during remission induction chemotherapy between 1 and 29 days. The St Jude Total XI Study protocol was used after some minor modifications in this trial. Patients were randomized into two groups. Group A (n = 108) received conventional dose (60 mg/m(2)/day orally) prednisolone and group B (n = 97) received HDMP (Prednol-L, 900-600 mg/m(2) orally) during remission induction chemotherapy. Complete remission was obtained in 95% of the 205 patients who were followed-up for 11 years; median follow-up was 72 months (range 60-129) and 8-year EFS rate was 60% overall (53% in group A, 66% in group B). The EFS rate of group B was significantly higher than of group A (P = 0.05). The 8-year EFS rate of groups A and B in the high-risk groups was 39% vs 63% (P = 0.002). When we compared 8-year EFS rate in groups A and B in the high-risk subgroup for both ages together /=10 years, it was 44% vs 74%, respectively. Among patients in the high-risk subgroup with a WBC count >/=50 x 10(9)/l, the 8-year EFS was 38% in group A vs58% in group B. During the 11-year follow-up period, a total of 64 relapses occurred in 205 patients. In group A relapses were higher (39%) than in group B (23%) (P = 0.05). These results suggest that HDMP during remission-induction chemotherapy improves the EFS rate significantly for high-risk patients in terms of the chances of cure.

Chronic hemolytic anemia associated with glucose 6-phosphate dehydrogenase (Guadalajara)1 159 C --> T (387 Arg --> Cys) deficiency associated with Gilbert syndrome in a Turkish patient.

The case of an 8-year-old male child with severe kernicterus sequelae is presented in this paper. The child's hemoglobin value varied between 6.0 and 10.8 g/dL and his reticulocyte count ranged between 3.4 and 46.0% during the steady-state condition and hyperhemolytic crisis, respectively. A chronic hemolytic type of red cell G6PD deficiency was diagnosed. DNA studies indicate that the mutation was G6PD Guadalajara 1159 C --> T (387 Arg --> Cys) that is situated at the NADP binding site. Additionally, extra nucleotides of (TA) in the A(TA)n TAA motif of the promoter region of the uridine diphosphate-glucuronosyltransferase gene (UGT-1 A) were found to be homozygous in the patient. The coexistence of Gilbert syndrome with a chronic type of G6PD deficiency was suggested as a cause of neonatal hyperbilirubinemia leading to kernicterus.

Evaluation of coagulation in pediatric bone marrow transplantation patients.

A hypercoagulable state is frequently described in adult patients undergoing bone marrow transplantation (BMT). In this study, the coagulation profile of 29 children was prospectively investigated in the pre- and post-transplant period. A significant rise in the activated partial thromboplastin time (aPTT) values was detected on days 7 and 14 after transplantation. Moreover, an increase in the d-dimer level was also notable, regardless of the clinical condition of the patients. The other coagulation parameters investigated (i.e. protein S, protein C, anti-thrombin III, factor VIII, von Willebrand factor, and prothrombin time) remained essentially unchanged. However, hyper-fibrinogenemia was observed in all patients with chronic myeloid leukemia (CML) (n=5) before and after transplantation. In summary, in the present study pediatric bone marrow transplantation patients did not show a hyper-coagulable state after marrow infusion. However, a significant rise in PTT and d-dimer values were noted.

Clinical importance of serum vascular endothelial and basic fibroblast growth factors in children with acute lymphoblastic leukemia.

The aim of this study is to evaluate, for the first time serum levels of vascular endothelial growth factor (s-VEGF), and basic fibroblast growth factor (s-b FGF) in children with acute lymphoblastic leukemia (ALL), and its relation to clinical manifestations of the disease. Although VEGF and b FGF have been suggested to be reliable prognostic indicators and important tools for treatment approach in malignant haematopoietic and solid tumours, experience in childhood ALL has been limited to only one study on angiogenesis and urine b FGF. All 31 ALL patients included in the present study at the time of diagnosis and in remission, and all 10 control children had detectable serum levels of VEGF and b FGF. The median level of s-VEGF at the time of diagnosis was significantly lower than in the control group and at the time of remission (respectively p = 0.005, p = 0.0001). Twenty six of 31 patients had an increasing trend of s-VEGF levels in remission reaching control values compared with the levels obtained at diagnosis. S-b FGF median levels at the time of diagnosis were the same as those of the control group, significantly lower than the median s-b FGF values in remission (p = 0.001). In patients with lower platelet counts (< 50 x 10(9)/L) growth factors (VEGF and b FGF) were lower than in patients with higher platelet counts (p = 0.0009 and p = 0.002 respectively). In patients with hepatosplenomegaly (longitudinal size > 3 cm) b FGF levels were higher than patients without hepatosplenomegaly (P = 0.003). We concluded that the increment in both s-VEGF and s-b FGF in patients in remission may be related to the renewal of normal haematopoiesis. The increase in s-VEGF values in 26 out of 31 patients in remission compared to normal control values, may also suggest that there is clinical significance in ALL patients.

Evaluation of children with myelodysplastic syndrome: importance of extramedullary disease as a presenting symptom.

Thirty-three children diagnosed with primary myelodysplastic syndrome (MDS) in a single institution over an 8 year period were evaluated with special emphasis on children who presented with extramedullary disease (EMD). EMD was present at diagnosis in 12 (36%) of the 33 children with MDS. Three patients with juvenile myelomonocytic leukemia (JMML) and 2 patients with chronic myelomonocytic leukemia (CMML) presented with pleural effusion. Pericardial effusion was present in 3 of these patients, two of whom also had thrombosis. Pyoderma gangrenosum, relapsing polychondritis were the initial findings in another two cases with JMML. Lymphadenopathy (n=1), gingival hypertrophy (n=2), orbital granulocytic sarcoma (n=1) and spinal mass (n=1) were the presenting findings in 5 patients with refractory anemia with excess of blasts in transformation. Since high-dose methylprednisolone (HDMP, 20-30 mg/kg/day) has been shown to induce differentiation and apoptosis of myeloid leukemic cells in children with different morphological subtypes of acute myeloid leukemia in vivo and in vitro, 25 children with de novo MDS were treated with combined HDMP and cytotoxic chemotherapy. Dramatic improvement of EMD and decrease in blast cells both in the peripheral blood and bone marrow were obtained following administration of short-course HDMP treatment alone as observed in children with AML. HDMP, combined with low-dose cytosine arabinoside and mitoxantrone were used for the remission induction. Remission was achieved in 8 (80%) of 10 children who presented with EMD and in 9 (60%) of 15 children without EMD. Long-term remission (>6 years) was obtained in 4 (two with JMML and two with CMML), three of whom presented with EMD. In conclusion EMD can be a presenting finding in childhood MDS as observed in adults. In addition, the beneficial effect of HDMP combined with more intensive chemotherapy should be explored as alternative therapy in children with MDS not suitable for bone marrow transplantation.

Relapse in hairy cell leukemia due to isolated nodular skin infiltration.

Leukemic skin infiltration is quite uncommon in certain types of leukemia. Here, a child with hairy cell leukemia who developed isolated skin infiltration during remission is reported. The failure to diagnose the leukemic infiltration until the nodule reached a diameter of 2 cm is emphasized.

Acute lymphoblastic leukemia in a child with Wilson disease.

Wilson disease is an autosomal recessively inherited disease of copper metabolism and is characterized by liver and central nervous system dysfunction. The heterozygote carrier state rate is about one in 90 persons and the incidence of the disease is about 30 in 1,000,000. Although leukemia is the most common form of childhood malignancies, the probability of the presence of Wilson disease and acute lymphoblastic leukemia in the same patient is very low. We report an unusual case of a child with Wilson disease who developed acute lymphoblastic leukemia in three months.

Acute parvovirus B19 infection mimicking juvenile myelomonocytic leukemia.

An 11-month-old patient with parvovirus infection mimicking juvenile myelomonocytic leukemia (JMML) is presented. The patient's history, presenting physical and laboratory features, was suggestive of JMML and consisted of fever, hepatosplenomegaly, lymphadenopathy, desquamation of the skin, anemia, leukocytosis with monocytosis and trilineage dysplastic findings of the peripheral blood and bone marrow. However, positive IgM titers for parvovirus B19 followed by seroconversion, negative cytogenetics and the benign follow-up of the patient suggested acute parvovirus infection as an etiologic factor for development of dysplastic features in the patient, and thus is recommended for consideration in the differential diagnosis of MDS. Although parvovirus B19 infection mimicking MDS has previously been shown in two patients with spherocytosis and one with subclinical immune deficiency; to our knowledge, the present report is the first describing the association of acute parvovirus B19 infection with dysplastic features mimicking myelodysplasia (MDS) in a child without a demonstrable underlying hematolymphoid disorder.

Triosephosphate isomerase deficiency with elevated sweat chloride test: report of a case.

A 15-month-old girl with severe hemolytic anemia and progressive respiratory failure is presented. She was well until the age of six months when she developed a pulmonary infection. During the next six months, she had frequent respiratory infections and her paleness became evident. At the age of 12 months, she was observed to have easy fatigability and muscle weakness, and she received her first blood transfusion. She was referred to our hospital at the age of 15 months. The physical examination revealed a malnourished girl with hypotonia, nystagmus, generalized muscle weakness and severe breathing difficulty requiring ventilatory support The hemoglobin (Hb) was 9.7 g/dl; hematocrit (Hct) 29%, mean corpuscular volume (MCV) 101 fl and reticulocyte count 15%. Peripheral blood smear revealed macrocytosis and stomatocytosis (30% of the red cells) and polychromasia. Sweat chloride test was 90 and 94 mEq/L on two separate occasions. The serum vitamin E level was 0.26 mg/dl (N: 0.44-0.68). She was found to be heterozygous for factor V Leiden mutation. Although malnutrition, low serum vitamin E and elevated sweat chloride test were suggestive of cystic fibrosis, this diagnosis failed to account for all the findings in the patient. A search for a red cell enzyme deficiency revealed that the red cell triosephosphate isomerase (TPI) activity was low. DNA analysis showed the 315 G-C (105 Glu-Asp) TPI mutation, thus confirming the diagnosis of TPI deficiency.

Loss of maternal allele in a child with myelodysplastic syndrome and monosomy 7.

Monosomy 7 or partial deletion of the long arm of chromosome 7 is frequently described in children with myelodysplastic syndrome and acute myeloblastic leukemia. Parental origin of chromosome 7 in children with sporadic monosomy 7 has been examined very rarely. To investigate if monosomy 7 shows parent-of-origin, we have studied a female child with monosomy 7 and de novo myelodysplastic syndrome by a series of polymorphic polymerase chain reaction markers. We found loss of maternal allele and discussed the results with the previous reports.

Differentiation of leukemic cells induced by short-course high-dose methylprednisolone in children with different subtypes of acute myeloblastic leukemia.

Differentiation of myeloid leukemic cells to mature granulocytes by high-dose methylprednisolone (HDMP, 20-30 mg/kg/day) with a favorable antileukemic effect has previously been demonstrated in children with acute promyelocytic leukemia and acute myeloblastic leukemia (AML) M4. In the present study, three children with other morphological subtypes of AML (two AML M1, one AML M2) were given methylprednisolone (30 mg/kg/day) orally in a single dose. After a short-course (3 or 7 days) of HDMP treatment alone, a striking decrease in blast cells associated with an increase in maturing and abnormally nucleated polymorphonuclear-like cells some containing Auer rods were detected in all patients in peripheral blood or bone marrow smears. During HDMP treatment, in parallel to morphological improvements, marked increases in the percentage of cells expressing granulocytic antigen (CD15) were observed. The increase of CD15 expression on myeloid cells, together with the steady expression of CD34 and CD117 antigens in Casel(AML M1) , is suggestive of aberrant CD34 + CD117 + CD15 + cells, which may indicate the leukemic origin of the maturing myeloid cells. These results suggest that HDMP treatment may induce differentiation of myeloid leukemic cells in some children with different morphological subtypes of AML, and that the differentiation-inducing effect of HDMP should be explored in other malignant diseases.

Autoimmune hemolytic anemia with warm antibodies in children: retrospective analysis of 51 cases.

In this paper, research based on 51 children with a positive antiglobulin test is presented. Eighteen of the children had acute anemia and 33 had chronic anemia. Two clinical patterns were distinguished: an acute transient type and a prolonged chronic type. Corticosteroid therapy was effective in all acute cases but its results were variable in the chronic cases. The acute form was more frequent in young children, while chronic autoimmune hemolytic anemia (AIHA) occurred mainly among children at puberty. In the chronic form of the disease, it was sometimes necessary to add immunosuppressive drugs and in two cases to perform a splenectomy.

Necrotizing otitis externa, otitis media, peripheral facial paralysis, and brain abscess in a thalassemic child after allogeneic BMT.

Severe infection is one of the major complications in the early and late post-bone marrow transplantation period. The authors report a thalassemic child who developed necrotizing otitis externa and otitis media, a very rare complication after bone marrow transplantation, and then peripheral facial nerve paralysis and brain abscess in the early period of bone marrow transplantation despite antibacterial and antifungal prophylaxis. Necrotizing otitis media is characterized by necrosis and sloughing of considerable areas in the middle ear and adjacent tissues and is an unusual disorder because of today's antibiotics. Granulocytopenia and background ear tissue exposed to previous repeated otitis media attacks may be the predisposing factors in this case. The authors conclude that the children with previous histories of recurrent otitis media should be prepared and monitored very carefully during bone marrow transplantation because of the risk of necrotizing otitis media, especially in the granulocytopenic period.

Dramatic resolution of pleural effusion in children with chronic myelomonocytic leukemia following short-course high-dose methylprednisolone.

High-dose methylprednisolone (HDMP) which can induce--differentiation and -apoptosis of myeloid leukemic cells has been shown to be very effective in the treatment of extramedullary infiltration (EMI) of children with acute myeloblastic leukemia (AML). In the present study 2 children with chronic myelomonocytic leukemia (CMML) who had pleural effusions were given a single daily dose of oral methylprednisolone (20 mg/kg or 30 mg/kg). In addition to dramatic improvement of respiratory symptoms, pleural effusions disappeared in four days in both patients possibly due to apoptotic cell death induced by HDMP treatment. Further studies are needed to determine whether high-dose corticosteroids are also effective on the resolution of pleural effusions associated with other malignant disease.