A clinicopathologic study of mantle cell lymphoma in a single center study in India.

We present clinical features, histopathology and results of treatment in cases of mantle cell lymphoma (MCL) at our hospital. We had 93 cases (2.1%) of MCL out of total 4301 cases of non-Hodgkin's lymphoma (NHL) in a 4-year period. It included 68 cases (1.7%) of MCL from 3987 cases of NHL diagnosed on histopathology. Remaining 25 cases (7.9%) diagnosed solely on peripheral blood examination were excluded. Thirty-six (85%) patients had advanced-stage disease. Sixty-three were nodal and five were extranodal (all gastrointestinal tract). Common patterns were diffuse (64%), nodular (25%) and mantle zone type (11%). Sixty-two cases had lymphocytic while six had blastic morphology (all nodal). Tumor cells expressed CD20 (100%), CD43 (94%), CD5 (89%) and cyclin D1 (85%). Bone marrow was involved in 25 (59%) cases. Thirty-two patients could be treated. Median recurrence-free survival was 22.23 months. Diffuse pattern of nodal involvement had a lower overall survival.

Activity and toxicity of 2-CDA in Langerhans cell histiocytosis: a single institutional experience.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder characterized by clonal proliferation of immature and abnormal bone marrow derived langerhans cells. Treatment is usually multimodal. Potent anti-monocyte as well as immunomodulatory activity of 2-CDA and its proven efficacy in many lymphoproliferative disorders has made 2-CDA a rational choice in treatment of LCH. AIM: To evaluate the efficacy and toxicity profile of 2-CDA in children with relapsed or refractory LCH. SETTING AND DESIGN: This is a pilot study and we present the initial data of the first seven patients treated at our institution. MATERIALS AND METHODS: Seven patients of relapsed and refractory LCH were enrolled from July 2000 to June 2004. The cohort of seven patients included six males and one female with a median age at initiation of cladribine was 2.25 years (range, 1.67 to 7.0 years). Three patients had received one prior chemotherapy regimen while the rest were heavily pretreated. Cladribine was administered over two hours IV daily for five days and repeated every four weeks. RESULTS: After a median of six courses of cladribine (range, 2 to 9), two (33%) patients achieved PR and two (33%) patients have SD on imaging but are clinically better. None experienced grade 3 or 4 hematologic toxicity. At a median follow-up of 19 months (range, 8 to 52 months), five patients remain alive and one patient has died. CONCLUSION: Our study shows that single agent 2-CDA is active and well-tolerated in children with relapsed or refractory LCH.

Metastatic gastric adenocarcinoma.

Gastrointestinal tumors represent less than 5% of all pediatric neoplasms. Within this subgroup carcinomas are rare, especially that of stomach. The authors present this rare entity with an equally rare presentation.

Low incidence of CNS relapse with cranial radiotherapy and intrathecal methotrexate in acute lymphoblastic leukemia.

OBJECTIVES: To assess the incidence of isolated central nervous system (CNS) relapses in patients of acute lymphoblastic leukemia (ALL) treated with a protocol containing cranial irradiation and intrathecal methotrexate as CNS directed therapy. DESIGN: Prospective non randomized study. SETTING: Department of Medical Oncology, Tata Memorial Hospital. SUBJECTS: 623 children of ALL on MCP 841. METHODS: CNS relapse was diagnosed, if upon examination of the CSF, more than 50 cells/microliter were observed, or a count of 5 cells which were unequivocally lymphoblasts. RESULTS: The incidence of isolated CNS relapse was 1.75% with the use of this treatment. Age, sex, white blood cell count, platelet count, lactic dehydrogenase and immunophenotyping were not significantly related to isolated CNS relapse. CONCLUSION: A low incidence of isolated CNS relapse demonstrates the adequacy of the presymptomatic CNS therapy.

Prognostic significance of DNA index by flowcytometry in acute lymphoblastic leukaemia.

DNA index (DI) is considered an important prognostic factor in acute lymphoblastic leukaemia (ALL). We undertook this study to correlate DI with other presenting features and response to therapy. Of the 30 patients of ALL treated at our hospital and entered in this study, 15 were put on the aggressive MCP (multi center protocol) 841 protocol and equal number on the Alternate protocol. Eighteen achieved complete remission (13/15 on the former protocol and 5/15 on the later). DI was less than 0.8 in 8 (27%) patients, between 0.8 and 1.2 in 18 (60%) and more than 1.2 in 4 patients (13%). These figures are different from those reported in Caucasians. On multivariate regression analysis, the DI significantly correlated with percentage of blasts in peripheral blood (P = 0.0035). There was no correlation with outcome or response to treatment.

Cytogenetic studies on patients of acute lymphoblastic leukemia Burkitt's type with (8;14) & (14;18) translocations.

Eight patients with acute lymphoblastic leukemia of Burkitt's type (ALL-L3) and two patients with Burkitt's lymphoma (BL) were subjected for cytogenetic studies. Translocation (8;14)(q24;q32) was present in nine (90%) patients; seven patients of ALL-L3 and two of BL. One ALL-L3 patient revealed t(14;18)(q32;q21) in 100 per cent metaphases. Additional clonal chromosomal anomalies present in these patients were deletion (6q) (40%) and trisomy 21(20%). The occurrence of t(8;14)(q24;q32) in ALL-L3 and BL patients in our series supports the association of t(8;14) with ALL-L3 and Burkitt's lymphoma.

Myelodysplastic syndrome. A clinical and pathological analysis of 88 patients.

Eighty eight patients with myelodysplastic syndromes were studied to determine the clinical and pathological features and the prognosis. All the patients had anemia. Neutropenia was seen in 44% and thrombocytopenia in 78% patients. The subtypes included refractory anemia in six, refractory anemia with ringed sideroblasts in three, refractory anemia with excess blasts in 30, refractory anemia with excess blasts in transformation in 32 and chronic myelomonocytic anemia in 17 patients. Forty four patients who received chemotherapy were evaluable for response. Three of the 15 patients treated with hydroxyurea achieved partial remission. Eighteen patients were treated with low dose cytosine arabinoside and complete remission was achieved in five and partial response in six patients. Aggressive chemotherapy was given to 11 patients at the onset of the illness resulting in complete remission in six and partial response in two patients. Nineteen of the 88 patients transformed to acute myeloid leukemia. The crude survival of all the patients ranged from 15 days to 22.5 months. The mortality was due to hemorrhage in 15% and septicemia in 85%. Our data reveals ineffectiveness of the current therapy and emphasizes on the need to develop newer therapeutic approaches.

Infantile neuroblastoma: 10 year TMH experience.

The results of 19 children with neuroblastoma under one year of age treated at the Tata Memorial Hospital between 1981-1990 were analysed. Biologically, neuroblastomas in children under the age of 12 months have an entirely different prognosis as compared to older children. There were four children less than six months of age and 15 children between six and 12 months. All patients with stage II (2/2) disease are alive; 3/4 patients with stage IV-S disease are disease free; 3/5 stage III patients are disease free and 2/8 patients with stage IV disease are disease free. The survival of infants with stage II and IV-S is better than for those with stage III and IV disease.

Prognostic significance of myeloperoxidase containing blast cells in acute myelogenous leukaemia.

Fifty three newly diagnosed patients of de novo acute myelogenous leukaemia (AML) received treatment consisting of remission induction with daunorubicin 60 mg/m2 on day one and continuous infusion of cytosine arabinoside 200 mg/m2/day over 24 h from day one to 7. Thereafter patients in complete remission received consolidation chemotherapy with two identical courses. Complete remission (CR) could be achieved in 40 patients (75.5%). Seven patients (13.2%) died with complications during aplasia phase following remission induction therapy while six patients (11.3%) had resistant disease. Twenty seven patients (67.5%) developed relapse while eight patients (15.1%) continue to remain in complete remission ranging from 51 to 68 months (median 62.5). The projected event free survival and disease free survival at 60 months is 15 per cent (SE + 11.9%) and 21 per cent (+6%) respectively. Evaluation of the prognostic significance of pretherapy characteristics showed that infection at presentation and low number of myeloperoxidase (MPO) containing blasts affected the achievement of complete remission adversely on univariate analysis. Similarly age at diagnosis, of more than 45 yr, total leucocyte count of 50,000/cumm or more and low number of MPO containing blasts affected the remission duration (disease free survival) adversely on univariate analysis. On multivariate analysis, MPO positivity of blast cells, remained the only significant independent characteristic. High MPO positivity affected the remission duration favourably (P < 0.01). Patients with high MPO positivity also achieved CR with one induction cycle in 32 out of 40 instances while only 2 out of 5 patients with low MPO positivity, achieved CR with one chemotherapy cycle (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Childhood myelodysplastic syndromes: clinical features, cytogenetics and prognosis.

Sixteen children with myelodysplastic syndrome as defined by the French-American-British co-operative group are presented. The mean age was 10.5 (2.5 to 16) years, with a male predominance. All patients belonged to the more aggressive subtypes of myelodysplastic syndromes. Seven patients presented with refractory anaemia with excess blasts, six had refractory anemia with excess blasts in transformation, and three had chronic myelomonocytic leukemia. Cytogenetic analysis done in 7 of the 16 patients, revealed karyotype abnormalities involving chromosomes 7, 8 and 17. One patient with Down's syndrome had karyotype of 47, XY, +21 (major clone) and 46, XY (minor clone). Five of these patients evolved to acute leukemia. The mean duration of survival was 5.5 months. Aggressive chemotherapy as a primary line of treatment induced remission in five out of six patients. Predominance of aggressive types of myelodysplastic syndromes in children and their good but short-lived response to aggressive chemotherapy suggests the need for early bone marrow transplantation following chemotherapy.

Cytotoxic therapy. Role of durable venous access.

Aggressive chemotherapy regimens and supportive measures in haemato-oncology patients demand reliable venous access. Experience with this method in India has been limited. During a period of six months, we have used 42 subclavian indwelling catheters and 31 cubital Cavafix long lines. The mean age of patients in the two groups was 32 years and 7 years respectively. Subclavian catheters had a median duration of catheter placement of 46 days (range 4-145) and total 1494 catheter days, while cubital longlines yielded a median duration of insertion of 14 days (range 4-27) and total 508 catheter days. Catheter related complications were infection in 25% of patients, thrombophlebitis in 22%, blockade in 12% and misplacement in 17% in both groups taken together. The patients and families were extremely satisfied with the devices. Our experience supports further use of durable venous access in cancer patients. Implanted central venous catheters should be preferred whenever feasible.

Acute non-lymphoblastic leukemia in children: prognostic factors and results of chemotherapy.

Twenty-nine children (age range 1-14, median 8 years) with acute non-lymphoblastic leukemia (ANLL) were induced in remission with daunorubicin and cytosine arabinoside. Twenty-three (79.3%) patients achieved complete remission (CR) and were administered two cycles of the same drugs as consolidation therapy; no maintenance treatment was given. Three (10.3%) patients died during induction; 3 (10.3%) patients were resistant to therapy. Multivariate analysis showed that female sex, TLC less than 50 X 10(9)/L, absence of in ection, albumin greater than 3.5 g/dl and high myeloperoxidase activity had a favourable influence on achievement of CR. TLC less than 50 X 10(9)/L and albumin greater than 3.5 g/dl also had a favourable prognostic value. Eight patients are alive between 13 and 32 months with overall survival at 2 years being 27.5%; four patients are free of disease with projected DFS at 2 years being 13.7%. The present data indicates the need for newer approaches to improve the long term survival in childhood ANLL.

Acute lymphoblastic leukemia in childhood: treatment, results and prognostic factors.

Two hundred and nine children (20 years and below) diagnosed as acute lymphoblastic leukemia between January 1980 and December 1983 were retrospectively analysed to evaluate the clinical features, prognostic factors and the results of therapy. One hundred and eighty one evaluable patients were treated with three different chemotherapy regimens consisting of vincristine and prednisolone (Group-A), vincristine, prednisolone and L-asparaginase (Group B-60 patients), and vincristine, prednisolone and adriamycin (Group C-81 patients). Complete remission was achieved in 152 (84%) patients, remission induction being 75 percent, 85 percent and 88 percent in Group A, B and C respectively. At a median follow-up of 36 months the disease free survival for complete responders was 35.5 patient. The disease-free survival for Group A, B and C was 20 percent, 47 percent 34 percent respectively indicating the superiority of a three drug regimen over the conventional two drug regimen. Patients at standard risk in each group had significantly better survival when compared to those at high risk. A 3-drug treatment regimen was superior to the 2-drug regimen and a low initial leucocyte count was an important favourable prognostic factor.

Limitations of the therapeutic regimens for myelodysplastic syndrome.

Thirty patients of myelodysplastic syndrome (MDS) were treated over a period of 2 yr using 3 different treatment regimens. Twelve patients received hydroxyurea, 4 were given low dose cytosine arabinoside and 14 others were treated with an aggressive acute myeloid leukaemia (AML) induction regimen. A low complete remission was obtained in the first 2 groups (17 and 25% respectively), whereas 9 (64%) patients attained complete remission with the AML induction regimen. Remission in the latter group was associated with prolonged and severe pancytopenia requiring intensive support. Patients in all the 3 groups had a short duration of remission culminating in death with progressive marrow failure or evolution to AML, indicating the limitations of the current treatment strategies for MDS and highlighting the need for exploring newer therapeutic approaches.

Multiple myeloma. Analysis of fifty cases.

Fifty patients of multiple myeloma have been studied. Seventy eight per cent of the patients were in the 5th, 6th and 7th decades of life. Commonest presenting feature was bone pains (76%). 8%, 20% belonged to stage I, II and III respectively. Skull (58%), ribs (52%) and pelvis (24%) were most commonly involved. Immunoelectrophoresis revealed IgG type of myeloma in 76% and IgA type in 10% cases. Bence-Jones proteinuria was seen in 60% of patients; Kappa specificity was commoner than lambda. Overall survival at 30 months was 50%. The survival was adversely influenced by advanced stage, higher plasma cell count in the bone marrow, low haemoglobin and high serum creatinine values.