Shano Naseem

Pediatric patients with bicytopenia/pancytopenia: Review of etiologies and clinico-hematological profile at a tertiary center

BACKGROUND The etiology of bicytopenia/pancytopenia varies widely in children, ranging from transient marrow viral suppression to marrow infiltration by fatal malignancy. Depending on the etiology, the clinical presentation can be with fever, pallor or infection. Knowing the exact etiology is important for specific treatment and prognostication. AIMS To evaluate the etiological and clinico-hematological profile in children with bicytopenia and pancytopenia. MATERIALS AND METHODS A review of bicytopenic and pancytopenic children referred for bone marrow examination from January 2007 to December 2008 was done. Detailed history, clinical examination and hematological parameters at presentation were recorded. RESULTS AND CONCLUSION During the study period, a total of 990 children were referred for bone marrow examination for different indications. Of these, 571 (57.7%) had either pancytopenia (17.7%) or bicytopenia (40%). Commonest form of bicytopenia was anemia and thrombocytopenia seen in 77.5% cases, followed by anemia and leukopenia in 17.3% and leukopenia and thrombocytopenia in 5.5% cases. Most common etiology was acute leukemia (66.9%) in bicytopenic children and aplastic anemia (33.8%) in pancytopenic children. Children with bicytopenia had a higher incidence of underlying malignancy (69.5% vs. 26.6%), splenomegaly (60.5% vs. 37.4%), lymphadenopathy (41.8% vs. 15.1%) and circulating blasts (64.6% vs. 20.1%) and a lower incidence of bleeding manifestations (12.1% vs. 26.6%) as compared to children with pancytopenia.

Primary bone marrow lymphoma is a rare neoplasm with poor outcome: case series from single tertiary care centre and review of literature†

Primary bone marrow lymphoma is a rare disease and remains undiagnosed due to deceptive clinical presentation. Here, we report four cases of primary bone marrow B‐cell non‐Hodgkin lymphoma, which presented with cytopenias without any lymphadenopathy or organomegaly. Bone marrow examination revealed large atypical B‐cells with a reactive T‐cell infiltrate with suppression of the normal hematopoietic elements. This lymphoma is known to have a poor prognosis. Inspite of treatment, two of our patients died during chemotherapy. Two patients relapsed, of which one showed an early relapse after two months and was put on an alternative regimen. The other patient relapsed twice at an interval of 4 and 5 years, respectively, following which he remained in remission for another 5 years and had recently shown a relapse for the third time. Review of literature revealed seven case series and 11 case reports of primary bone marrow lymphoma in the last five decades.

Homozygosity mapping reveals founder SEC23B‐Y462C mutations in Indian congenital dyserythropoietic anemia type II

F1P1 V F 8 6.2 8.8 390 2 LM 1:1 ND CDA II band 3 Y462C/Y462C F2P1 V M 9 5.5 12.5 384 <0.2 LM 1:4 ND CDA II band 3 Y462C/Y462C F3P1 V M 6 10.8 6.4 368 0.4 LM 1:2 POS CDA II band 3 Y462C/Y462C F4P1 V M < 1 7.5 4.1 311 2.5 LM, EM 1:5 ND CDA II band 3 Y462C/Y462C F4P2 V M < 1 7.1 4.1 282 3.3 LM, EM 1:3 ND ND Y462C/Y462C F5P1a V M 21 8.4 3.2 301 2.6 LM, EM 1:3 ND CDA II band 3 Y462C/Y462C F6P1a V F 16 9.1 4.1 288 2.9 LM, EM 1:3 ND CDA II band 3 Y462C/Y462C F7P1a V F 17 7.6 5.4 221 4.2 LM, EM 1:2 ND CDA II band 3 Y462C/Y462C F8P1 V M 7 7 5.9 243 2 LM, EM 1:3 ND ND Y462C/Y462C F9P1 V M 6 5.3 6.1 210 1.6 LM, EM 1:3 ND ND Y462C/Y462C F10P1 V F 2 10.7 11 279 1 LM, EM 1:2.5 POS ND Y462C/Y462C F11P1 V M 7 6.2 7.1 289 1.2 LM, EM 1:4 ND ND Y462C/Y462C F12P1 V M 5 3.7 12.1 276 2 LM 1:1 POS ND Y462C/Y462C F13P1 V F 10 8.2 10.2 588 2.8 LM 1:3 ND ND Y462C/Y462C F13P2 V M 26 9.8 8.3 243 3.4 LM 1:4 ND ND Y462C/Y462C F14P1 V F 14 6.8 2.4 157 1.8 LM 1:4 ND ND Y462C/Y462C F15P1 V F 9 7 13.5 200 0.5 LM 1:1.2 POS ND Y462C/Y462C F16P1 V/O M 1 6.5 5.7 271 ND LM ND ND ND Y462C/WT F17P1 V/O M 1 7 7.8 431 ND LM, EM 1:4.5 ND ND Y462C/WT F18P1 V M 2 7.6 18.8 290 6.5 LM, EM 1:1 ND ND ND F19P1 V M 13 10.9 8.1 256 0.4 LM, EM 1:2 POS ND ND F20P1 V F 1 6.5 11.3 285 4.5 LM, EM 1:1 POS ND ND F21P1 V M 5 7.8 10.8 559 2.8 LM 1:3.5 POS ND ND F22P1 V F 6 9.1 15.9 340 3.5 LM NA POS ND ND F23P1 O F 10 6.4 4.9 459 3 LM 1:2 POS CDA II band 3 WT/WT F24P1 O M 4 7.5 7.6 335 NA LM 1:2.5 ND CDA II band 3 WT/WT F24P2 O M 4 6.3 11.7 439 1.5 LM, EM 1:3.5 POS CDA II band 3 WT/WT F25P1 O F 4 6 4.4 330 NA LM, EM 1:4 POS CDA II band 3 WT/WT

Paroxysmal Nocturnal Hemoglobinuria is rare cause for thrombosis of the intra-abdominal veins in the ethnic Indian population - results from FLAER-based flowcytometry screening.

Paroxysmal nocturnal hemoglobinuria (PNH) may present as cytopenia, hemolysis, or thrombosis at unusual sites including splanchnic vessels. Thrombosis of the portal veins and hepatic veins are associated with thrombophilic risk factors: deficiencies of protein C, protein S, and antithrombin, positivity for antiphospholipid antibodies, and factor V Leiden mutation. There is limited information regarding PNH presenting primarily as a thrombotic event. We prospectively screened 142 consecutive patients with intrabdominal thrombosis and 106 controls with fluorescently labeled inactive toxin aerolysin (FLAER)‐based flowcytometry to assess the frequency of PNH as a thrombophilic risk factor in patients with intra‐abdominal thrombosis.

Detection of paroxysmal nocturnal hemoglobinuria-phenotype in patients with chronic lymphocytic leukemia and multiple myeloma

BACKGROUND Paroxysmal nocturnal hemoglobinuria (PNH) results due to decrease or absence of glycosylphosphatidylinositol-anchored (GPI) molecules, such as CD55 and CD59, from the surface of the affected cells. PNH-phenotype has been described in various hematological disorders, mainly aplastic anemia and myelodysplastic syndromes; recently it has been reported in patients with lymphoproliferative syndromes and multiple myeloma (MM). MATERIALS AND METHODS We evaluated the presence of CD55 negative and/or CD59 negative red blood cell (RBC) populations in newly diagnosed treatment naive-54 chronic lymphocytic leukemia (CLL) and 29 MM patients by flow cytometry. RESULTS PNH-phenotype was not reported in any patient; however, RBC populations deficient in CD55 were detected in 16.66% (9/54) CLL and 6.89% (2/29) MM patients. Clinical presentation or the hematological parameters did not show any relationship with the presence of CD55 deficient RBC population. CONCLUSION Our study showed absence of PNH-phenotype in patients with CLL and MM; however, isolated CD55 deficient RBC were identified in both CLL and MM. Larger prospective studies by other centers, including simultaneous analysis of granulocytes for the presence of PNH-phenotype, are needed to corroborate these findings and to work out the mechanisms and the significance of the existence of this phenotype in these patients.

Application of flow cytometry in pediatric hematology-oncology†

Applications of flow cytometry in pediatric cancers have expanded substantially in recent years. In acute leukemias, the commonest childhood cancer, flow cytometry can now define complex antigenic profiles that are associated with specific cytogenetic/molecular defects and can also directly identify BCR‐ABL fusion protein. Flow cytometry based scoring system has been described for diagnosis of myelodysplastic syndromes. In solid tumors, flow cytometry was previously used mainly to determine DNA content for prognosis; however, recent studies in children with neuroblastoma and Ewing sarcoma have identified its diagnostic utility. In this review, we will discuss the current and future applications of flow cytometry in pediatric hematology‐oncology. Pediatr Blood Cancer 2011;57:18–29.

Synchronous Occurrence of Prostate Carcinoma and Multiple Myeloma: A Case Report

We describe a rare case of metastatic prostate cancer to bone marrow and synchronous multiple myeloma as the second malignant disease. Various diagnostic procedures, including cytomorphology and immunohistochemistry analyses together contributed to the detection of metastasis of prostate cancer and synchronous plasma cell proliferation in the bone marrow. The association between these two disorders is poorly understood however, some studies show that bone marrow microenvironment may play a crucial role. The need for further research in this regard is required to unfold this fascinating association.

Factors Affecting Early Molecular Response in Chronic Myeloid Leukemia

OBJECTIVES There is controversy about whether 3- or 6-month molecular assessment predicts progression-free and overall survival in those with chronic myeloid leukemia (CML). The factors predicting molecular response at 3, 6, and 12 months have not been studied extensively. The study objective was to study the factors affecting molecular response at 3 and 6 months in patients with CML who are receiving imatinib mesylate. METHODS We prospectively enrolled patients with newly diagnosed CML who were receiving imatinib mesylate as the initial therapy for CML. The diagnosis of CML was based on clinical examination, bone marrow, and demonstration of BCR ABL(IS) transcripts by polymerase chain reaction. The molecular response(IS) was assessed at 3, 6, and 12 months by GeneXpert (Cepheid, Sunnyvale, CA) and co-related with various baseline characteristics of patients. We also looked at whether early achievement of a complete hematologic response within 6 weeks predicts molecular response at 3 or 6 months. The study took place at a tertiary care hospital in Northwest India catering to patients belonging to low-middle socioeconomic status. RESULTS We enrolled 131 patients with CML in the chronic phase from July 1, 2013, to August 31, 2014. The median age of the patients was 40 years (range, 13-67) with a male preponderance (61% were male). Most patients presented with symptoms of low-grade fever (52.7%) and abdominal fullness (26.7%). Spleen was palpable in 84.7% of patients. The median hemoglobin at presentation was 10.8 g/dL (range, 4.8-18.4 g/dL), white cell count was 138.3 × 10(9)/L (4.1-697 × 10(9)/L), and platelet count was 326 × 10(9)/L (85-1819 × 10(9)/L). The median number of peripheral blood basophils was 3% (range, 0%-20%), and blasts were 3% (range, 0%-10%). Myelofibrosis of more than grade 1 was present in 30% of patients. Most patients belonged to intermediate Sokal (45.8%) and Hasford (55%) scores and low EUropean Treatment Outcome Study (78.6%) score. Of 128 evaluable patients at 3 months, 96.9% achieved complete hematologic remission (CHR) and 82.3% achieved BCR ABL(IS) of less than 10%. None of the patients who had BCR ABL(IS) > 10% at 3 months achieved BCR ABL(IS) < 1% at 6 months or < 0.1% at 12 months. Early achievement of CHR (< 6 weeks), peripheral blood blast count of < 5%, and lactate dehydrogenase < 851 U/L were significantly associated with achievement of BCR ABL(IS) < 10% at 3 months and BCR ABL(IS) < 1% at 6 months. CONCLUSIONS We found that BCR ABL(IS) assessment at 3 months is superior to assessment at 6 months. Patients with CML in the chronic phase who achieve CHR within 6 weeks are more likely to achieve BCR ABL(IS) < 10% at 3 months and < 1% at 6 months than patients who achieve CHR between 7 and 12 weeks.

T-lineage acute lymphoblastic leukemia and parvovirus infection in a child with neurofibromastosis-1.

Neurofibromatosis (NF-1) patients have an increased risk of developing malignancies most commonly rhabdomyosarcomas, optic gliomas, brain tumors and non-lymphocytic leukemias. Acute lymphoblastic leukemia (ALL) has been infrequently reported in association with NF-1. We describe a rare association of NF-1, T-lineage ALL and parvovirus infection in a 12-year-old child. In addition, it is also to emphasize that a high index of suspicion should be kept for parvovirus B19 infection as a cause of bicytopenia/pancytopenia in ALL patients following induction chemotherapy.

Primary/de novo paroxysmal nocturnal hemoglobinuria in a child from north India: a case report with review of literature.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematologic disorder, characterized by intravascular hemolysis, thrombosis, or bone marrow failure. It is very rare in children. The clinical manifestations are due to deficiency of a family of membrane proteins that are anchored into the cell membrane through glycosylphosphatidylinositol (GPI). Currently, flow cytometric analysis of GPI-linked proteins has replaced the traditional Ham test (acidified-serum lysis test) and sucrose lysis test, it being a quantitative and more sensitive method. The only curative treatment of the disease is stem cell transplantation. We are reporting a case of de novo pediatric PNH, presenting with hemoglobinuria and a sizeable clone of GPI-anchor deficient blood cells, along with review of reported cases of PNH in pediatric patients. PNH can occur in children and has varied clinical and hematologic presentations; the presence of PNH should be considered in every child with an acquired bone marrow failure, unexplained hemoglobinuria and/or unexpected serious thrombosis. Pediatricians should keep this disorder in mind, when patients present with above features.