Rapidly Progressing Plasma Cell Leukemia with Underlying Plasmablastic Morphology: A Rare Case Report of a 25-Year Old Male.

Multiple myeloma constitutes a wide spectrum of diseases, ranging from slow-growing monoclonal gammopathy of undetermined significance to rapidly progressing plasma cell leukemia. It is a very rarely diagnosed hematological malignancy in those less than 30 years of age. A 25-year-old male presented with complaints of fatigue and low-grade fever. On investigation, he was found to have bicytopeina and features of tumor lysis syndrome. Initially, this was thought to be indicative of acute leukemia. However, upon further analysis with bone marrow biopsy, serum protein electrophoresis, and immunofixation, it was determined that the patient had an IgG myeloma with plasmablastic morphology. It rapidly progressed and the peripheral smear started showing clusters of plasma cells suggesting a picture of plasma cell leukemia. The patient succumbed to this aggressive disease despite treatment. This case illustrates that myeloma should also be included in the differential diagnosis for young patients, especially the rare plasmablastic variant, which can be misdiagnosed as acute leukemia. The aggressive morphology also tends to show rapid progression to plasma cell leukemia, which has a poor prognosis.

CML in Elderly: Does Age Matter?

The median age of diagnosis for chronic myeloid leukemia (CML) in India is 35 years on the contrary to western literature which is 47 years. The outcome of the elderly patient in CML TKI era is not reported from the Indian population. However, Western literature suggests that use of TKI alleviate the adverse impact of age in outcomes of CML. This study was carried out to analyze the clinical profile and outcome of elderly, in comparison with younger patients with CML. We retrospectively analyzed CML patients treated at our department from January 2008 to December 2017. The data cutoff date was December 2018. The cohorts of 712 patients were divided into two groups. Patients belonging to the age group of ≥ 60 years were classified as the study group and those who were 18-60 years were used as controls. Patient's clinical history, examination and milestones in terms of achieving hematological, molecular responses and toxicity profile were also recorded. The total of 712 patients, 52 patients in the study group and 660 patients in the control group were treated during the study period. The study group was having more co-morbidities than the control group (15.3% vs. 4.5%). Patients having high-risk EUTOS score were similar in both groups (38.4% vs. 37.6%). The patients presented in blast phase were higher in the study group as compared to control group (9.6% vs. 6.36%) but the differences were not statistically significant. Rates of achieving a hematological response at 3 months (85.1% vs. 86.89%) and the major molecular response at 18 months (54.3% vs. 60.16%) were almost similar in both groups. However, hematological toxicity, muscle cramps and gastritis were reported more in elderly patients. The outcome of CML patients in TKI era do not differ in elderly patients. However, toxicity profile was not significantly inferior in elderly patients.

T-Cell Prolymphocytic Leukemia: An Experience from a Tertiary Cancer Centre in South India.

Background: T-cell prolymphocytic leukemia (T-PLL) is a rare lymphoid malignancy with dismal prognosis. Most patients have increased lymphocyte count (>1,00,000/dL) and widespread disease at presentation. Despite high response rate seen with alemtuzumab, the disease relapse is inevitable. Materials andMethods: This was a retrospective observational study done at a tertiary cancer center in South India. All patients diagnosed with T-PLL from August 2010 to July 2015 were studied for the clinical characteristics, pathological findings and treatment outcomes. Results: Seven patients were diagnosed as T-PLL over a period of 5 years. The median age at diagnosis was 51 years. In the present series, 6 patients (86%) had splenomegaly and 3 had hepatomegaly (43%). Generalized lymphadenopathy was seen in 4 (57%) patients at presentation. Skin lesions were seen in 5 (71%) patients, whereas pleural effusion was seen in only one patient (14%). All had elevated total leukocyte count, with more than 1, 00,000/dL in 4 patients. The median survival was 5 months with different chemotherapy (CT) regimens (5 patients treated with CT and 2 received best supportive care). Conclusion: T-PLL is a rare disease with no definite treatment guidelines. At present, the best outcomes are achieved if treatment with alemtuzumab is followed by stem cell transplant, but the disease invariably relapses. Countries where affordability remains a big challenge, the best approach needs to be defined beyond the monoclonal antibodies and transplant.

Study of clinical, haematological and cytogenetic profile of patients with acute erythroid leukaemia.

BACKGROUND: Acute erythroid leukaemia (AEL) is a rare subtype of acute myeloid leukaemia (AML), constituting <5% of all the cases of AML. The World Health Organization (WHO) in 2001 classified AEL into two types: (1) erythroid/myeloid leukaemia which required ≥50% erythroid precursors with ≥20% of the non-erythroid cells to be myeloid blasts and (2) pure erythroleukemia (pEL) with ≥80% erythroblasts. The WHO 2008 classification kept these subcategories, but made erythroleukemia a diagnosis of exclusion. There are very few studies on the clinico haematological and cytogenetic profile of this disease, considering the rarity of its occurrence and poor prognosis. MATERIALS AND METHODS: This study was done by retrospective analysis of data from 32 case files of patients diagnosed with AEL. Clinical details noted down were the demographic profile, peripheral blood smear details and bone marrow examination details: (1) blasts-erythroblasts and myeloblasts, (2) dysplasia in the cell lineages and (3) cytogenetic abnormalities. RESULTS: The most common presenting symptom was fever. Pancytopenia at presentation was seen in 81.25% of patients. Dysplasia was observed in bone marrow in 100% of erythroblasts and in 40% of myeloblasts in erythroid/myeloid subtype. In pure myeloid subtype, myeloid and megakaryocytic dysplasias were not obvious. Complex karyotype was noticed only in patients of pEL. CONCLUSION: AEL is a rare group of heterogeneous diseases with many neoplastic and non-neoplastic conditions mimicking the diagnosis. The clinical presentation and cytogenetics are also non-specific, presenting additional challenges to the diagnosis.

G-banding and fluorescence in situ hybridization in childhood acute myeloid leukemia from South India.

BACKGROUND: The current WHO classification of hematologic malignancies defines distinct entities of myeloid disorders based on the presence of recurrent cytogenetic abnormalities. Diagnostic clonal chromosomal abnormalities provide important prognostic information and are among the most important factors in predicting initial response to chemotherapy, duration of remission and overall survival.  METHODS: This study analyzed chromosomal abnormalities in bone marrow aspirates of 50 children diagnosed with acute myeloid leuckemia (AML).  RESULTS: The culture success rate was 94%, clonal chromosomal abnormalities constituted 62% and recurrent chromosomal abnormalities were 56%. In the favorable prognostic category, there were 51.6% of cases with t(8;21)(q22;q22), 16.1% had t(15;17)(q22;q21), and a total of 12.9% had chromosome 16 rearrangement. The adverse risk category showed a low frequency of t(9;11)(p22;q13); t(1;22)(p13;q13); inv(3)( q21q26); add 4(q35) and ring chromosome. According to fluorescent in situ hybridization (FISH) results in 16 cytogenetically normal patients, there were no CBFß/MYH11 fusion genes observed in chromosome 16 rearrangements.  DISCUSSION: Larger studies of this kind may provide more information about chromosome 16 rearrangements in cytogenetically normal patients. The present analysis suggests that both age and cytogenetics are important strategies for risk stratification (outcome). Additional laboratory parameters should also be considered in childhood AML.

Wilms' tumor: single centre retrospective study from South India.

Wilms' tumor is the most common malignant renal tumor in paediatric age group, and is classically managed by multimodal treatment which involves surgery, radiotherapy and chemotherapy. The last few decades have seen a dramatic change in the prognosis of this disease, which once was a uniformly lethal malignancy. While there is plenty of data in world literature on the outcome of Wilms' tumor, there is paucity of data from India. Hence, we conducted the present study to analyze the outcome of Wilms' tumor at our institute. To study the clinicopathologic profile and outcome of Wilms' tumor with NWTS (National Wilms' Tumor Study Group) IV protocol. Sixty-one patients with histopathological proven diagnosis of Wilms' tumor and had received treatment at our institute from Jan 2003 through Dec 2010 were included for analysis. Patients received treatment based on NWTS IV protocol. Patients were analysed for overall survival and event free survival and these outcomes were correlated with age, sex, stage at presentation and histology. Favourable histology which included focal anaplasia was found in 80.3 % while unfavourable histology was elicited in 19.7 % of the cases. The estimated 5 year event-free survival was 83.3 % and overall survival was 85.2 %. Tumour histology was the single most important factor predicting the survival. Patients with childhood Wilms' still present very late in our setting, this poses management challenges as large tumor are technically difficult to deliver at surgery. Histology has a crucial role in outcome of this disease. With multidisciplinary approach, similar survival rates to National Wilms' Tumor Study Group seems to be achievable even in Indian scenario.

Rare and recurrent chromosomal abnormalities and their clinical relevance in pediatric acute leukemia of south Indian population.

BACKGROUND AND OBJECTIVES: This cytogenetic study detects a wide variety of common, rare and novel chromosomal abnormalities in patients with hematological disorders, providing valuable diagnostic and prognostic information. MATERIALS AND METHODS: We addressed the utility of the cytogenetic technique in 50 patients of pediatric acute leukemia prospectively. RESULTS: Successful cultures were found in 44 patients (88%) and abnormal karyotypes in 22 (44%). The common abnormalities like hyperdiploidy, del(6q), t(1;19)(q23;p13), t(4;11)(q22;q23), t(9;22)(q34;q11), rare t(2;7)(q23;p11) and t(4;12)(q21;p13) and a novel translocation t(7;9)(q22;q21) were observed in acute lymphoblastic leukemia. In acute myeloid leukemia, t(8;21)(q22;q22), del(16)(q22), t(15;17)(q22;q21) and t(9;11)(p22;q23) were commonly seen. CONCLUSION: Chromosomal abnormalities of this small group of patients are compared with the relevant literature with respect to the incidence rate and prognosis.

Combined study of cytogenetics and fluorescence in situ hybridization (FISH) analysis in childhood acute lymphoblastic leukemia (ALL) in a tertiary cancer centre in South India.

FISH is one of the most sensitive molecular methods to detect genetic abnormalities with DNA probes. When cytogenetic studies are normal or insufficient, FISH may detect cryptic rearrangements, rare or slowly proliferative abnormal populations in non-mitotic cells. We cytogenetically evaluated 70 childhood ALL - 67.1% were found to have an abnormal karyotype. The 23 patients (32.9%) with a normal karyotype were analyzed by FISH applying two probes; TEL/AML1 and MYB which detect cryptic rearrangements of t(12;21)(p13;q22) and deletion of (6q) respectively, associated with a good prognosis. Out of 23 patients, one was positive for t(12;21)(p13;q22) (4.3%). None of our patients were positive for MYB del(6q). Two patients showed an extra signal for MYB on chromosomes other than 6 (8.6 %) indicating amplification or duplication. Findings were compared with the available literature. Our study clearly indicated the integrated FISH screening method to increase the abnormality detection rate in a narrow range. FISH is less useful for diagnostic study of patients with suspected del(6q) but it helps in detecting known cryptic rearrangements as well as identification of new abnormalities(translocation , duplication and amplification) at the gene level.

Bone marrow involvement at presentation in pediatric non-haematological small round cell tumours.

Pediatric small round cell tumors (SRCT) are a group of neoplasms occurring in children, which have in common a cytomorphology of groups of small round cells with scanty cytoplasm. The common SRCT encountered are neuroblastoma, retinoblastoma, Ewing's sarcoma/peripheral neuroectodermal tumor (PNET), rhabdomyosarcoma and lymphoma which show varying degrees of bone marrow involvement and bone marrow evaluation forms a part of the initial staging procedure. This study was undertaken to evaluate marrow involvement at presentation in pediatric non hematological SRCT. 7833 bone marrow aspirates done over a period of three years in different malignancies were analysed and of these 180 aspirates were performed in patients of pediatric non hematological SRCT at presentation. These cases were evaluated in detail for incidence of marrow involvement. Thirty two (17.7%) cases showed marrow involvement and these cases have been analysed with respect to the primary tumor. The SRCT showing involvement of bone marrow included neuroblastoma (48.8%), retinoblastoma (11.1%), Ewing's sarcoma/PNET (8.6%) and rhabdomyosarcoma (3.2%). These findings are discussed in the light of available world literature.

del(2)(p23) as a sole abnormality in a case of acute myeloid leukemia.

We report a case of acute myeloid leukemia (AML) [FAB-M5a] showing a deletion of the short arm of chromosome 2 at band p23 as a sole abnormality in the bone marrow cells. This abnormality deserves to be considered as an established nonrandom entity in AML.

The rheumatological prodrome: an unusual inaugural manifestation of acute myeloblastic leukemia.

Uncommon patterns of presentation of acute leukemia pose diagnostic problems. A rheumatological prodrome in acute myeloblastic leukemia is very rare. We describe one such patient who had a normal haemogram. Bone marrow examination done later revealed acute myeloblastic leukemia. The case is discussed with reference to literature.