Pegfilgrastim: More Cost Effective and Equally Efficacious Option as Compared to Filgrastim in Autologous Stem Cell Transplant.

Use of growth factor after high-dose chemotherapy (HDC) and autologous peripheral blood stem cell (PBSC) support is current standard in reducing days of neutropenia. This retrospective study aims to compare the efficacy of two standard growth factors, pegfilgrastim (PEG) and filgrastim (FIL) after HDC. We collected data on 195 consecutive adult patients who received an autotransplant (myeloma, lymphoma and others) between January 2004 and December 2014 at two tertiary care centres. The primary end point was the duration of neutropenia in terms of days to reach an ANC > 0.5 × 109/L. Filgrastim was given to 110 patients and PEG was given to 85 patients. Time to engraftment, defined as the time to reach an ANC of 0.5 × 109/L on 2 consecutive days after the day of auto-SCT, was 12.6 days with FIL compared with 12.1 days with PEG group (p = 0.126). When comparing the total days of severe neutropenia (WBC < 0.1 × 109/L), there were 5.5 days of severe neutropenia with FIL compared with 5.8 days with PEG group (p = 0.7). The duration of febrile neutropenia was an average of 5.3 days with FIL and 4.6 days with PEG (p = 0.029). The total number of antibiotic days was shorter for the patients who received PEG, being 11.08 days with PEG and 12.1 days with FIL (p = 0.184).The average cost savings per person in terms of number of days of hospitalization and number of days of total parental nutrition was 582 Rs (p = 0.512) and 6003 Rs (p = 0.018) respectively in favour of PEG arm. PEG is similar to FIL in hematological reconstitution, however it is more cost effective alternative after HDC and PBSC.

Engraftment Syndrome: Clinical Features and Predictive Factors in Autologous Stem Cell Transplant.

Engraftment Syndrome (ES) maybe observed in patients who undergo autologous stem cell transplant (SCT). To investigate clinical criteria for ES diagnosis and analyse the risk factors for this complication, we reviewed all auto-SCT cases (Lymphoma and Myeloma) performed during the past 9 years at two tertiary care centres. We analysed all patients with a non-infectious fever, developed within 7 days of engraftment (first day of ANC of 500 on two consecutive days) in 178 patients undergoing autologous stem cell transplant. A total of 46/178 (25.8%) patients developed non-infectious fever and one or more clinical signs of ES within 7 days of engraftment. In all, 29 (61%) fulfilled the Maiolino and 12 (26%) the Spitzer criteria. The incidence of engraftment syndrome using the Maiolino criteria in our study was 29 (15%), which compares well with Spanish study (13% using same criteria) and the original Maiolino study (20%). All patients with ES satisfactorily recovered and discharged with a median of 20 days from hospital. There was no significant difference in number of days of hospitalisation and days of antibiotics between the ES and non ES arms. All patients recovered without any morbidity and only 1 (2%) patient required readmission for fungal pneumonitis. 8 (17%) patients required ICU admission due to delay in initiation of steroids. None of the factors including number of chemotherapy cycles, conditioning regime, disease status, CD34 collection, growth factors and day of WBC engraftment except female (p = 0.064) were statistically significant (in univariate or multivariate analysis). Our study shows that engraftment syndrome is common in autologous transplant setting. Maiolino criteria to diagnose ES is more sensitive in our setting. If detected and treated early there is not much morbidity or mortality related to ES.

Highly elevated serum CA 125 in a lady with ascites and retroperitoneal mass--a diagnostic dilemma.

BACKGROUND: Cancer antigen 125 (CA 125), a widely used tumor marker for monitoring epithelial ovarian cancer, is also found to be raised in non-gynecological tumors and non malignant disease involving peritoneum. We report a case of non-Hodgkin's lymphoma who presented with peritoneal and pleural effusions with a very high level of serum CA 125. CASE: Fifty four years female presented with gross ascitis, bilateral moderate pleural effusions, right retroperitoneal mass and a very high serum CA 125 level (4462.60 u/ml). She was initially evaluated to rule out ovarian malignancy but her biopsy from retroperitoneal mass came out to be diffuse large B cell non-Hodgkin's lymphoma. CONCLUSION: In a female patient with ascitis with high serum CA 125 level, a differential diagnosis of lymphoma should not be overlooked unless cytology comes positive for epithelial carcinoma cells.

Imatinib mesylate in chronic myeloid leukemia: a prospective, single arm, non-randomized study.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder characterized by the balanced reciprocal translocation t (9:22). The resulting fusion gene, the BCR-ABL, is responsible for oncogenesis. Imatinib mesylate is a novel molecule, which inhibits the protein product of this fusion gene and hence has been used in the treatment of CML. The present study evaluates 174 patients with CML treated with imatinib mesylate. Of these 174 patients, 97 were in chronic phase, 47 in accelerated phase and 30 patients had blast crisis. Patients in chronic phase received imatinib mesylate in the dose of 400-mg daily, while those in accelerated phase and blast crisis received 600 to 800 mg daily. Of the 97 patients with chronic phase, 49 patients (50.5%) achieved a major (major + complete) cytogenetic response. Of the 47 patients in accelerated phase, 10 patients (21.3%) achieved a major cytogenetic response and in 30 patients with blast crisis, 7 (23.3%) achieved a major cytogenetic response. Dermatitis, mucositis, neutropenia and thrombocytopenia were some of the major toxicities. Of interest, 121 of the 174 patients (69.5%) developed generalized hypopigmentation. We conclude that imatinib mesylate is a safe and effective first-line therapy for chronic myeloid leukemia.

Outcome of acute myeloid leukaemia in adults: a retrospective analysis.

BACKGROUND: There are little data from India on the management of acute myeloid leukaemia. With better understanding of the biology of the disease, and routine use of high-dose cytarabine as post-remission therapy with or without haematopoietic blood stem cell transplantation (HSCT), the results have improved in the past two decades. We analysed our results in a cohort of recently treated patients. METHODS: A total of 166 newly diagnosed patients with AML (excluding acute promyelocytic leukaemia), 15-60 years of age were treated with daunorubicin (60 mg/m2/day x3 days) or idarubicin (12 mg/m2/day x3 days) with cytarabine (100 mg/m2/day continuous i.v. infusion x7 days) induction chemotherapy. Post-remission therapy included 2 cycles of high-dose cytarabine (15-18 g/m2) followed by monthly cycles of outpatient maintenance chemotherapy x4 cycles, consisting of daunorubicin (45 mg/m2 i.v. x1 day and cytarabine 100 mg/ m2 s.c. twice daily x5 days). Six patients in remission received sibling donor allogeneic HSCT. RESULTS: Morphological complete remission was achieved in 69.9% of the patients. Resistant disease after induction chemotherapy was seen in 14.6% and early mortality occurred in 16%. Relapse-free survival and event-free survival at a median of 36 months was 34% and 22%, respectively. Relapse occurred in 43.9%. The median duration of remission was 12 months. CONCLUSIONS: Our results conform to the published literature from larger cooperative studies from the West. Currently available cytotoxic drugs are unlikely to improve the results any further.

Primary non-Hodgkin's lymphoma of the bone: a single institution experience.

UNLABELLED: Primary non-Hodgkin's lymphoma of the bone is an unusual entity. Twenty-five patients with diffuse large cell lymphoma of the bone were registered at the Tata Memorial Hospital (TMH) from August, 1991, to May, 2002. Pain at the local site and soft tissue swelling were the commonest symptoms. Involvement of the bones in the lower half of the body was more frequent than the bones in the upper half. Osteolytic lesions and an associated soft tissue mass were the common radiological findings. Nineteen patients received CHOP chemotherapy and five received COP chemotherapy. Twenty-three patients received involved field radiotherapy. The overall response to therapy was 96%. On follow-up, two patients had a nodal relapse. One patient died of progressive disease, and one patient died of cryptococcal meningitis. There were no deaths due to treatment-related toxicity. The mean progression free survival was 9.39 yr and the overall survival was 11.66 yr. The median overall survival has not been reached. At last follow-up, 21 patients were being following up at TMH and are free of disease. CONCLUSION: Primary bone lymphoma is a malignancy that is highly curable with a combination of chemotherapy and radiotherapy.

Activation of HHV-6 in lymphoproliferative disorders: a polymerase chain reaction-based study.

HHV-6 is a latent herpes virus persisting throughout the adult life of the infected host in an integrated form and is often activated in immunocompromised situations. Detection of HHV-6 DNA in the plasma of an individual indicates the presence of active viral replication in the host. Because lymphomas are known to be associated frequently with host immunosupression, we studied activation of HHV-6 in 98 patients diagnosed with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL). HHV-6 activation was documented in 34% of cases of non-Hodgkin's lymphoma and 39% of those of Hodgkin's disease; however, no correlation of activation status with pathological types of Hodgkin's disease and between copy numbers in peripheral blood mononuclear cell DNA and the corresponding plasma DNA was noticeable.

Allogeneic blood stem cell transplantation in chronic myeloid leukaemia-chronic phase following conditioning with busulphan and cyclophosphamide: a follow up report.

BACKGROUND: Allogeneic bone marrow transplantation (BMT) or peripheral blood stem cell transplantation remains the only modality of treatment that can eradicate a leukaemia clone in the majority of patients with chronic myeloid leukaemia (CML). However, the advent of the targeted molecule imatinib mesylate (formerly STI-571) against the bcr-abl chimeric protein in the disease has brought the issue of managing newly diagnosed CML patients, especially those with available donors, to the crossroads. Although the curative potential of this agent remains unknown, it can produce complete cytogenetic response in > 60% of newly diagnosed patients. METHODS: From May 1991 to October 2002, a total of 55 Ph+ CML-chronic phase patients received oral busulphan 16 mg/kg and cyclophosphamide 120 mg/kg i.v. as a conditioning regimen. All patients received human leucocyte antigen (HLA)-identical sibling donor haematopoletic stem cells--bone marrow in 41 patients (74.5%) and peripheral blood stem cells in 14 (25.4%). Post-transplant prophylaxis for graft-versus-host disease included a short course of methotrexate (on days +1, +3, +6 and +11) and cyclosporin till day +180 in 38 patients (69.1%), while a combination of cyclosporin and methylprednisolone was used in the remaining 17 (29%). RESULTS: At a median follow up of 48 months (10-144 months), 26 patients (47.3%) are alive. Early mortality (100-day) occurred in 17 patients (30.9%). Acute graft-versus-host disease developed in 37 patients (67.3%), and was grade IV in 6 of them. Chronic graft-versus-host disease developed in 17 patients (30.9%). Relapse occurred in only 2 patients (3.6%) till date. The leukaemia-free survival is 64.3% in the peripheral stem cell group, whereas it is 41.5% in the bone marrow recipient group. CONCLUSION: Allogeneic BMT appears to result in eradication of CML and ensure disease-free survival in about half the patients. However, efforts should be made to prevent graft-versus-host disease and minimize early mortality.

Consolidation radiation after complete remission in Hodgkin's disease following six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy: is there a need?

PURPOSE: Combined modality treatment using multidrug chemotherapy (CTh) and radiotherapy (RT) is currently considered the standard of care in early stage Hodgkin's disease. Its role in advanced stages, however, continues to be debated. This study was aimed at evaluating the role of consolidation radiation in patients achieving a complete remission after six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy using event-free survival (EFS) and overall survival (OS) as primary end points. PATIENTS AND METHODS: Two hundred and fifty-one patients with Hodgkin's disease attending the lymphoma clinic at the Tata Memorial Hospital (Mumbai, India) from 1993 to 1996 received induction chemotherapy with six cycles of ABVD after initial staging evaluation. A total of 179 of 251 patients (71%) achieved a complete remission after six cycles of ABVD chemotherapy and constituted the randomized population. Patients were randomly assigned to receive either consolidation radiation or no further therapy. RESULTS: With a median follow-up of 63 months, the 8-year EFS and OS in the CTh-alone arm were 76% and 89%, respectively, as compared with 88% and 100% in the CTh+RT arm (P =.01; P =.002). Addition of RT improved EFS and OS in patients with age < 15 years (P =.02; P =.04), B symptoms (P =.03; P =.006), advanced stage (P =.03; P =.006), and bulky disease (P =.04; P =.19). CONCLUSION: Our study suggests that the addition of consolidation radiation helps improve the EFS and OS in patients achieving a complete remission after six cycles of ABVD chemotherapy, particularly in the younger age group and in patients with B symptoms and bulky and advanced disease.

Successful allogeneic stem cell transplantation with fludarabine-based conditioning regimen in severe aplastic anemia.

Graft failure is a problem in HLA-identical sibling transplants for patients with refractory severe aplastic anaemia (SAA). Intensification efforts includes addition of radiation or biologic agents such as antithymocyte globulin (ATG), procarbazine or cyclophosphamide has often been advocated to combat this problem. With this approach engraftment rate has improved. However the incidence of transplant related complications are also increased, resulting in little change in the overall outcome. We therefore investigated the use of combination of fludarabine and cyclophosphamide as a non-myeloablative conditioning regimen in a patient who was refractory to multiple immunosuppressive agents and transfusions. He received peripheral blood stem cells from his HLA-identical sibling donor. With a follow up of eighteen months, the patient is alive with complete and durable hematopoietic engraftment. Fludarabine-based conditioning regimen therefore has the potential to be successfully and safely used in patients with SAA undergoing transplant.

Use of a reduced-intensity conditioning regimen for allogeneic transplantation in patients with chronic myeloid leukemia.

Reduced-intensity conditioning that harnesses the potential of a graft-versus-tumor (GVT) effect has been proposed as an alternative to conventional myeloablative allogeneic stem cell transplantation. The primary aim is engraftment and this can be achieved with minimal immunosuppression. In this report, we describe the use of such regimens for CML in 17 patients who received human leukocyte antigen (HLA)-matched sibling allografts. Conditioning was with fludarabine, antithymocyte globulin (ATG) and busulfan for the first 11 patients, whereas fludarabine, busulfan and TBI were used for the remaining six patients. Engraftment was prompt in most of the cases. Complications and need for supportive therapy in the immediate post-transplant period were reduced drastically. Only two patients (both in the TBI group) died within the first 100 days. Acute graft-versus-host disease (GVHD) grade II-IV was seen in seven patients. Complications occurred later on. Chronic GVHD was observed in 11/17 patients. Lung infection and GVHD were the major killers. In surviving patients, after a median follow-up of 30 months (range 37-21 months), 6/17 (35.3%) are alive. Five are disease free and one patient is still in relapse even after a second donor lymphocyte infusion. Total treatment time and cost were more than with conventional transplants. We conclude that reduced-intensity transplantation still requires further refinement.

Fluorescence in situ hybridization: a highly efficient technique of molecular diagnosis and predication for disease course in patients with myeloid leukemias.

The accuracy of cytogenetic diagnosis in the management of hematological malignancies has improved significantly over the past 10 years. Fluorescence in situ hybridization (FISH), a technique of molecular cytogenetics, has played a pivotal role in the detection of unique sub-microscopic chromosomal rearrangements that helped in the identification of chromosomal loci, which contain genes involved in leukemogenesis. We studied the feasibility and sensitivity of the FISH technique for molecular analysis of translocations markers, t(9;22) and t(15;17) for accurate molecular diagnosis and for monitoring the disease in 21 patients with chronic myeloid leukemia (CML) who received interferon-alpha and/or chemotherapy (7 patients), bone marrow transplantation (14 patients), and 14 patients with acute promyelocytic leukemia (APL) who received all-trans-retinoic acid (ATRA) and/or chemotherapy. We also applied conventional karyotyping (CK) for identification of t(9;22) and t(15;17) at diagnosis. All CML cases had a Ph; t(9;22) and except for two cases all APL had t(15;17). The FISH studies on CML marrows in complete cytogenetic remission (CCR) (100% Ph- by CK) achieved by IFN-alpha, showed 0-2.5% of cells with BCR-ABL fusion in first cytogenetic remission (Controls, range 0.5-1.5%). Repeat follow-up FISH studies could be done in two cases in remission, which demonstrated 0-10% of cells with BCR-ABL fusion. Evaluation of Ph positive status of CML marrow at diagnosis by CK (100% Ph+ cells) and FISH (80-92% BCR-ABL fusion) pointed the existence of dormant clone of normal residual hematopoietic cells along with actively proliferating clones of Ph positive cells. Fluorescence in situ hybridization analysis of post-BMT CML marrows in CCR (0% Ph+ mitoses) could detect MRD with range of 1-6%. Among 14 patients, 9 who showed percentage of BCR-ABL positive cells (0.0-1.5%) almost similar to normal controls, 6 patients had comparatively good prognosis (disease-free survival 7-14 months). Of five patients with residual leukemic cells in the range of 2-6%, 4 relapsed within a period of 3-24 months. Fourteen APL patients in CCR [100% t(15;17) negative cells by CK] were evaluated by FISH to check the presence of residual leukemic cells. In these patients FISH could efficiently detect 1-14.5% of residual cells with PML-RARA (patients mean MRD 5%, controls mean MRD 3.5%, P=.02). Since the time of FISH analysis, 5 to 7 patients with higher fraction of leukemic cells (5-11%) relapsed within a short period (1-7 months). On the contrary, 5 of 7 patients with either absence or low percentage of PML-RARA positive cells remained in complete remission for 11-24 months. Our data show that FISH has a potential to detect and measure the fraction of aberrant malignant cells in remission marrows, induced by BMT in CML and chemotherapy in APL. These findings encourage the investigations on a large scale to merit its potential for identification of patients at high risk. In the present studies, FISH on interphase cells also demonstrated its efficiency in the molecular diagnosis by its ability to detect BCR-ABL and PML-RARA fusion in CML with masked/variant Ph and t(15;17) negative APL, respectively. The efficiency of technique in molecular diagnosis was also proved in one of the CML patients who progressed to myeloid blastic phase where interphase FISH could identify an extra BCR-ABL fusion on both chromosomes 9 indicating insertion of BCR into ABL and its duplication.

Gynecomastia in a case of hairy cell leukaemia--cladribine induced?

Gynecomastia is benign enlargement of the male breast and is commonly drug induced. Various drugs are responsible and chemotherapeutic drugs can also cause gynecomastia. Cladribine is now widely used for the treatment of hairy cell leukaemia. We present a case report of development of unilateral gynecomastia in a case of hairy cell leukaemia treated with cladribine and question whether this was induced by the chemotherapy.

Mycobacterial pulmonary infection post allogeneic bone marrow transplantation.

Allogeneic bone marrow transplant recipients are prone to pulmonary infections caused by a wide spectrum of organisms. Since the first bone marrow transplatation (BMT) done in 1983 at the Tata Memorial Hospital, we have recently seen the first case of Mycobacterium Fortuitum Chelonae complex among 117 BMT (including 90 allogeneic and 27 autologous) patients. The patient was on immunosuppressants for chronic GVHD post allogeneic BMT done for CML-CP. He developed pulmonary mycobacterial infection 13 months post BMT. Diagnosis was difficult because of the atypical presentation, negative culture reports, and the presence of multiple pathogens due to immunosuppression. In our case the diagnosis was eventually established after examination of material obtained by bronchoscopy. Patient has shown response to antituberculosis drugs after 2 months. This shows the need to consider atypical mycobacterial infection in the differential diagnosis of pulmonary illness in the post allogeneic BMT setting.

2-CdA in the treatment of hairy cell leukaemia.

INTRODUCTION: Hairy cell leukaemia (HCL) is a rare lymphoproliferative disorder. Treatment options available are splenectomy, interferon, DCF and 2-CdA. 2-CdA is considered to have curative potential as proved by the other studies. METHODS: We gave 2-CdA in a dose of 0.09/kg/day as a continuous infusion in sixteen patients of hairy cell leukaemia. RESULTS: Three patients developed neutropenia post transfusion. At the end of three months all patients were in remission. Two patients relapsed at the median follow-up of 15 months. CONCLUSION: 2-CdA in HCL can achieve complete remission, prolonged survival and care as well.

Palliation of malignant colonic obstruction by self-expandable metal stent.

Advanced obstructive colorectal cancer is routinely treated by surgical colostomy. Self-expandable metal stents are a promising alternative. We report the use of an expandable metal stent to relieve colonic obstruction in an elderly lady with advanced colorectal malignancy.

Epstein-Barr virus association in classical Hodgkin's disease provides survival advantage to patients and correlates with higher expression of proliferation markers in Reed-Sternberg cells.

BACKGROUND: Most Epstein-Barr virus (EBV) associated lymphoproliferative disorders have high proliferation indices. However, classical Hodgkin's disease (cHD) is heterogeneous, with respect to proliferation index of the Reed-Sternberg cell (RS cell), and EBV association. Hence, we investigated whether cHD with and without EBV-association differ with respect to the proliferation index of the RS cells. Further we investigated whether this would have a bearing on patients survival. PATIENTS AND METHODS: We investigated 110 cases of cHD for: a) EBV association by immunohistochemical demonstration of EBV-latent membrane protein-1 and EBV encoded nuclear RNA 1 by mRNA in situ hybridisation; b) Proliferating cell nuclear antigen (PCNA) expression in the RS cells. RESULTS: EBV association was noted in 86 of 110 cases (78%). Higher PCNA expression (P = 0.004) and younger age (P = 0.001) correlated independently with EBV association. The 10 year relapse free survival (RFS) of EBV+ and EBV- patients were 60% and 44%, respectively (P = 0.03). The 10 year overall survival (OS) of EBV+ and EBV- patients were 85% and 64%, respectively (P = 0.03). EBV association maintained its significant impact on RFS and OS within Cox proportional hazard model. CONCLUSIONS: Our study suggests that EBV is likely to confer a higher PCNA expression and also contribute towards maintaining the RS cells of cHD in cell cycle. Hence, RS cells in EBV associated cHD would be more responsive to chemotherapy and radiotherapy associated DNA damage. Thus, EBV-association provides survival advantage to cHD patients treated with standard chemotherapy and radiotherapy protocols.

Hydroxyurea induced leg ulcers.

A 34 years non diabetic lady with chronic myeloid leukaemia (CML) was treated with hydroxyurea and interferon. She developed leg ulcers. First time on left toe and three months later on right foot, a rare complication of hydroxyurea. Both were treated with local wound care and antibiotics. First time dose of hydroxyurea was reduced and second time drug was discontinued.