Outcome of Acute Myeloid Leukemia in Children Adolescents and Young Adults Treated with an Uniform Protocol in Casablanca, Morocco.

Treatment of acute myeloblastic leukemia in children, adolescents and young adults (AYA) is a challenge in low-income countries. To evaluate treatment outcomes of children (≤ 15 years) and AYA (15-30 years) diagnosed with novo AML and treated in a single center according to the AML-MA 2011 protocol. From January 2011 to December 2015, eligible patients (age ≤ 30 years) with novo AML had been enrolled on a uniform treatment protocol. The diagnosis was confirmed according to the FAB classification using the WHO 2008 criteria. Patients with WBC ≥ 50 G/L had pretreated 4 days of hydroxyurea followed by two inductions and two consolidations. Supportive care consisted of transfusion of labile blood products, antibiotics and antifungals, and patient and family education by the hygiene team. 155 patients were recruited, 41 were < 15 years old (22 boys, median age 7.8 years). Of the 114 AYA enrolled, (48 women, median age 23 years). Complete remission after two inductions was 28/41 (68.3%) of the children, including 100% of the children in the favorable group and 71/114 (62.3%) of the AYA, 22 of whom (68.7%) were in the favorable group. The number of deaths among children was 6 (14.6%). The evaluation of the AML-MA-2011 National Protocol in the age groups of children and AYA reveals that the objective of treatment is almost achieved in terms of complete remission in the two age groups.

Effectiveness of antibacterial prophylaxis during induction chemotherapy in children with acute lymphoblastic leukemia.

BACKGROUND: Pediatric patients receiving induction chemotherapy for newly diagnosed acute lymphoblastic leukemia (ALL) are at high risk of developing life-threatening infections. We investigated whether uniform antibacterial guidelines, including mandatory antibacterial prophylaxis in afebrile patients during induction, decreases the incidence of microbiologically documented bacteremia. METHODS: Between 2012 and 2015, 230 patients with newly diagnosed ALL (aged 1-21) were enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 11-001 (DFCI 11-001). Induction therapy, regardless of risk group, included vincristine, prednisone, doxorubicin, methotrexate, and PEG-asparaginase. Afebrile patients received fluoroquinolone prophylaxis at the initiation of induction and those presenting with fever received broad-spectrum antibiotics; antibiotics were continued until blood count recovery. Rates of documented bacteremias and fungal infections on DFCI 11-001 were compared to those on the predecessor protocol (DFCI 05-001), which included the same induction phase without antibiotic prophylaxis guidelines. RESULTS: Sixty-six (28.7%) patients received fluoroquinolone prophylaxis, the remaining patients received broad-spectrum antibiotics. Twenty-four (36.4%) patients on prophylaxis developed fever and seven (10.6%) developed bacteremia. The overall rate of infection during induction on DFCI 11-001 was lower than on DFCl 05-001 (14.3% vs. 26.3%, P < 0.0001) due to a decreased rate of bacteremia (10.9% vs. 24.4%, P < 0.0001). The rate of fungal infections (4.8% vs. 3.6%) and induction death (0.9% vs. 2%) was not significantly different. CONCLUSION: For children with newly diagnosed ALL, uniform antibiotic administration until blood count recovery, including fluoroquinolone prophylaxis for afebrile patients, reduced the incidence of bacteremia during the induction phase. Larger, randomized studies should be performed to confirm these findings.

Biology and outcome of childhood acute megakaryoblastic leukemia: a single institution's experience.

To describe the clinical and biologic features of pediatric acute megakaryoblastic leukemia (AMKL) and to identify prognostic factors, experience at St Jude Children's Research Hospital was reviewed. Of 281 patients with acute myeloid leukemia treated over a 14-year period, 41 (14.6%) had a diagnosis of AMKL. Six patients had Down syndrome and AMKL, 6 had secondary AMKL, and 29 had de novo AMKL. The median age of the 22 boys and 19 girls was 23.9 months (range, 6.7-208.9 months). The rate of remission induction was 60.5%, with a 48% rate of subsequent relapse. Patients with Down syndrome had a significantly higher 2-year event-free survival (EFS) estimate (83%) than did other patients with de novo AMKL (14%) or with secondary AMKL (20%; P < or =.038). Among patients who had de novo AMKL without Down syndrome, 2-year EFS was significantly higher after allogeneic bone marrow transplantation (26%) than after chemotherapy alone (0%; P =.019) and significantly higher when performed during remission (46%) than when performed during persistent disease (0%; P =.019). The 5-year survival estimates were significantly lower for de novo AMKL (10%) than for other forms of de novo AML (42%; P <.001). Treatment outcome is very poor for patients with AMKL in the absence of Down syndrome. Remission induction is the most important prognostic factor. Allogeneic transplantation during remission offers the best chance of cure; in the absence of remission, transplantation offers no advantage over chemotherapy alone. (Blood. 2001;97:3727-3732)

Use of reverse transcriptase polymerase chain reaction for diagnosis and staging of alveolar rhabdomyosarcoma, Ewing sarcoma family of tumors, and desmoplastic small round cell tumor.

PURPOSE: To compare the use of reverse transcriptase polymerase chain reaction (RT-PCR) with that of morphology-based methods for diagnosis, staging, and detection of metastatic disease in pediatric alveolar rhabdomyosarcoma (ARMS), Ewing sarcoma family of tumors (ESFT), and desmoplastic small round cell tumors (DSRCT). MATERIALS AND METHODS: RT-PCR assays for the EWS-FLII, EWS-ERG, PAX3-FKHR, PAX7-FKHR, and EWS-WTI fusion transcripts were performed on RNA extracted from the primary tumor tissue, bone marrow, and body fluids obtained at initial presentation and relapse. Molecular findings were compared with original histologic diagnoses and results of staging procedures. RESULTS: Eighty-eight samples from 47 patients with ARMS (n = 13), ESFT (n = 31), or DSRCT (n = 3) were analyzed. The detection rate of metastatic disease was significantly higher with RT-PCR (95%) as compared with the morphologic methods (70%) for the three pediatric sarcomas studied. In primary tumors with characteristic fusion transcript, RT-PCR was positive in all cases with morphologic evidence of metastatic disease. Moreover, in six patients (3 with ARMS, 2 with DSRCT, and 1 with ESFT) with metastatic disease, micrometastases in bone marrow (4) and other sites (2) were detected by RT-PCR alone. Importantly, none of the patients with localized disease diagnosed had micrometastases detected by RT-PCR in bone marrow. CONCLUSIONS: The high sensitivity and specificity of RT-PCR for the characteristic fusion transcripts of pediatric sarcomas make it an ideal method to aid in the routine staging of these patients. In addition, the 100% sensitivity of RT-PCR in detection of micrometastasis makes it useful for follow-up and detection of minimal residual disease. However, the clinical significance of molecularly-detectable disease remains unknown. Further studies should aim to elucidate the therapeutic and prognostic implications of micrometastases detected by RT-PCR alone.

Splenic rupture in children with hematologic malignancies.

BACKGROUND: Splenic rupture is an uncommon but life-threatening complication of leukemias and lymphomas, and is reported mostly in adults. The authors investigated the frequency with which splenic rupture is diagnosed in pediatric patients with hematologic malignancies and reviewed its clinical profile and outcome. METHODS: The data base of St. Jude Children's Research Hospital was searched for cases coded as splenic laceration or rupture, splenic infarction, or splenectomy in patients diagnosed with lymphoma or leukemia between January 1962 and December 1997. The medical records of patients with histopathologic or radiologic evidence of splenic rupture were reviewed. The time spanned by the study was divided into early (1962-1990) and recent (1991-1997) eras to reflect the availability of modern diagnostic imaging techniques. RESULTS: Seven children experienced splenic rupture. They were between ages 5-17 years. There were four males and three females. Primary diagnoses included acute myeloid leukemia (four patients), acute lymphoblastic leukemia (two patients), and Hodgkin lymphoma (one patient). Five patients were diagnosed in the recent era and two in the early era. Four patients had radiologic or bacteriologic evidence of fungal infection concomitant with the splenic event. Of five deaths, only two were related causally to splenic rupture; these occurred in the early era. All seven acute episodes of splenic rupture were managed conservatively without surgery. CONCLUSIONS: The overall frequency with which splenic rupture was detected in children with hematologic malignancy at the study institution was 0.18%. In the recent era, the frequency of detection was 9-fold higher (0.55%) than that of the early era (0.06%). Improved imaging techniques and increased utilization of imaging studies may account for the increased incidental detection of "preclinical" splenic rupture. Adolescent age group, acute myeloid leukemia (especially acute promyelocytic leukemia), a high leukocyte count, thrombocytopenia, and coagulopathy may predispose children with leukemia to pathologic splenic rupture. Fungal infection frequently was associated with splenic rupture and may play a role in its pathogenesis.

Poland's syndrome and Wilms tumor: an unusual association.

Poland's syndrome, a rare congenital disorder with pectoralis muscular girdle defect, have been reported in association with lymphoreticular malignancies in the past. Childhood solid tumors in association with this congenital anomaly have not been reported so far. We describe this rare association of Poland's syndrome and Wilms tumor. Due to the possibility of increased risk of leukemogenesis in patients with Poland's syndrome, chemo-radiation therapy of Wilms tumor in our patient may increase the risk of secondary leukemia. Therapeutic modification of primary cancer in these patients may be necessary with careful long-term follow-up for early detection and treatment of secondary cancer.

Childhood cancers in Zambia before and after the HIV epidemic.

Human immunodeficiency virus (HIV) related cancers in children are not as common and as well described as in adults. An HIV epidemic has been prevalent in Zambia since 1983-1984. To study the effect of the epidemic on the epidemiology of cancers in children a retrospective study was undertaken at the University Teaching Hospital (UTH), Lusaka, Zambia. All the histopathological records from 1980 to 1992 were reviewed and all cases of cancers in children less than 14 years of age were analysed. In order to define the effect of the HIV epidemic, the epidemiological features of various childhood cancers occurring before (during the years 1980-1982) and after (during the years 1990-1992) the onset of the HIV epidemic were compared. A significant increase in the occurrence of total childhood cancers was found. This is mostly due to a highly significant increase in the incidence of paediatric Kaposi's sarcoma (p = 0.000016), which is causally related to HIV infection, and a significant increase in the incidence of retinoblastoma (p = 0.02), which has an unknown relation to HIV infection. Though not yet statistically significant, there has also been a gradual and sustained increase in the incidence of non-Hodgkin's lymphoma, nasopharyngeal carcinoma, and rhabdomyosarcoma. There has been a significant reduction in the incidence of Burkitt's lymphoma. A prospective in depth epidemiological study of HIV related childhood cancers in Africa is urgently needed.

Plasmodium falciparum malaria in vivo drug sensitivity in Lusaka, Zambia.

In most of sub-Saharan African, drug resistant falciparum malaria has become a major health care concern. Drug sensitivity was evaluated in vivo in Lusaka, Zambia, in 71 episodes in 61 patients with uncomplicated falciparum malaria, for Chloroquin (CQ), Pyrimethamine/sulfadoxine (PS) and halofantrine (HF). CQ resistance was found at R2 (16 pc) and R3 (24.5 pc) level in 37 patients, R3 (10.5 pc) resistance to PS was found among 19 subjects studied. The drug resistance to CQ was inversely related to age.

Influence of HIV epidemic on the incidence of Kaposi's sarcoma in Zambian children.

Acquired immunodeficiency syndrome-associated Kaposi's sarcoma (KS) is well documented in adults. However, very little information is available about KS in the pediatric age group. A retrospectively study was undertaken at the University Teaching Hospital (UTH), Lusaka, Zambia, to define the incidence and clinical profile of KS in Zambian children over the last 13 years and to determine the influence, if any, of the current human immunodeficiency virus (HIV) epidemic on the pattern of pediatric KS. All the histopathological records from 1980 to 1992 were reviewed and all cases of KS along with the total number of malignancies, both in children and adults, were analyzed. Along with this, 17 of 23 case files of pediatric KS patients treated at the UTH since 1984 were retrieved and clinical details recorded. Of a total of 915 cases of KS, 85 (9.25%) were in children < 14 years of age. The age ranged from 7 months to 14 years, with an average of 5.62 years; the male/female ratio was 1.76:1. A significant increase in the incidence of pediatric KS has been recorded since 1987 (p < 0.001). This coincides with the advent of the HIV epidemic in the country. The disease was aggressive and fulminant in pediatric patients. More than 80% HIV seropositivity was detected. Children with blood transfusion-related HIV infection had cutaneous or lymphocutaneous disease, indicating that the mode of acquisition of HIV infection may influence the clinical appearance of KS. Thus, HIV-associated KS in children is becoming a common entity in Zambia. An urgent prospective epidemiologic study is needed to address this problem in HIV-affected regions.

Clinical analysis of mortality in hospitalized Zambian children with sickle cell anaemia.

The hospital records of 62 Zambian children with sickle cell anaemia (SCA) who died during a 3 year period (January 1987 to December 1989) at the Paediatric Wing of the University Teaching Hospital, Lusaka, Zambia, were reviewed retrospectively. The SCA patients accounted for 2.92 percent of the total admissions and the average case fatality was 6.61 percent of the total SCA admissions. The case fatality rate has reduced considerably as compared to the one observed in 1970 in Zambia, although the major causes of death remain the same. The maximum mortality was noted in the age group of one to five years (54.84%). The common causes of death were infections (29.54%), vasoocclusive crises (22.72%) and splenic sequestration crises (20.45%). The problems of sub-Saharan Africa, like malaria, malnutrition and now the HIV infection also adde to the mortality (15.90%).

PIP: Physicians analyzed the hospital records of 62 sickle cell anemia (SCA) patients who were admitted to the pediatric wing of the University Teaching Hospital in Lusaka, Zambia, between January 1987 and December 1989 and who died. They examined the case fatality rate and the causes of death. During this period, SCA patients comprised 938 of the 31,843 pediatric admissions (2.95%). The case fatality rate of these 938 urban SCA patients was 6.61%, which is much lower than the 1970 rate of 18.57%. The researchers attributed the lower case fatality rate to the comprehensive health care provided by the hospital's sickle cell disease clinic, established in 1971. Sickle cell-related deaths during the study period made up 0.97% of all pediatric deaths. The case fatality rate was 20.17% for all pediatric admissions. SCA-related mortality peaked in the 1-5 year old age group (38.71%) followed by the 6-10 year old age group (20.97%). As for causes of death, the case records of only 44 sickle cell-related deaths were available. The pediatricians were not able to specify the exact clinical diagnosis in 18 case files (29.03%). The major categories of causes of death were infections (29.54%), vaso-occlusive crises (22.72%), and splenic sequestration crises (20.45%). The infections included 6 cases of bronchopneumonia, 4 cases of confirmed malaria, 1 case of pneumococcal meningitis, and 1 case of HIV infection with cardiomyopathy. The researchers were not sure whether the HIV infection or SCA caused cardiomyopathy. An earlier study at the hospital found HIV seroconversion in more and more SCA patients. This study's major obstacles were poor record keeping, poor communication channels, inability to conduct autopsies due to social and cultural reasons, procedural delays, and unavailability of pathologists. These obstacles must be addressed to improve knowledge on death in SCA patients.

Aniridia--Wilms' tumour association--a case with 11p 13-14.1 deletion and ventricular septal defect.

A two year old female child with bilateral wilms tumor (WT) along with multiple congenital anomalies like bilateral aniridia with congenital cataracts and nystagmus, microcephaly, mental retardation and ventricular septal defect has been described. The karyotype analysis revealed 46 xx, del 11p 13-14.1. Association of ventricular septal defect with the classical features of 'Aniridia-Wilms' tumor association' is an unusual feature in this case.

Fanconi's anemia: a clinico-hematological and cytogenetic study.

Eleven patients with typical features of Fanconi's anemia with cytogenetic studies were evaluated. Cytogenetic abnormalities was seen in all but one patient. Two patients had acute non-lymphoblastic leukemia (ANLL) and nine had Fanconi's anemia (FA). All patients with FA responded to oxymetholone and are well with a median follow up of 38.6 months. Both patients with ANLL died. This study stresses the need of an accurate cytogenetic analysis in FA patients along with a clinicohematological correlation.