Nehal Masood

Outcome of match related allogeneic stem cell transplantation procedures performed from 2004 till 2011

We present our initial experience of allogeneic stem cell transplant procedure performed between April 2004 and August 2011 for various haematological disorders. All patients with non-malignant and malignant haematological disorders with HLA matched donors were selected after pre-transplant workup. Ninety seven patients underwent the procedure. Most common indications for transplant were aplastic anaemia in n = 34 (35%), followed by β-Thalassemia major in n = 21 (21.6%) and chronic myeloid leukemia in n = 11 patients (11.3%). Primary graft failure present was present in 2.06%. Incidence of graft versus host disease (GvHD) in our patients was 34%. After median follow-up of five years the overall survival was 71.3% with a mean survival time of 51.2 ± 3.3 months.

Outcome of febrile neutropenic patients on granulocyte colony stimulating factor in a tertiary care hospital.

INTRODUCTION Febrile neutropenia is a relatively frequent event in cancer patients treated with chemotherapy and improvement in absolute neutrophil count (ANC) has been linked directly to improved outcome. Evaluation of granulocyte colony stimulating factors (GCSFs) for treatment has shown reduced incidences of episodes of prolonged neutropenia and protracted hospitalization. To determine absolute neutrophil counts with GCSF in febrile neutropenic cancer patients admitted to a tertiary care centre and to co-relate the improvement in ANC with mortality and hospital discharge. METHODS A prospective cross sectional study was carried at an oncology ward at Aga Khan University hospital from January 2010 to June 2011. All adult patients who were admitted and treated with GCSF for chemotherapy induced febrile neutropenia were included. Multivariable regression was conducted to identify the factors related with poor outcomes. RESULTS A total of 131 patients with febrile neutropenia were identified with mean age of 43.2 (18-85) years, 79 (60%) being ≤ 50. Seventy-five (57%) had solid tumors and 56 (43%) hematological malignancies, including lymphoma. Fifty seven (43.5%) had an ANC less 100 cells/mm(3), 34 (26%) one between 100-300 cells/mm(3) and 40 (31%) an ANC greater than 300 cells/mm(3). Thirty (23%) patients showed ANC recovery in 1-3 days, and 74(56%) within 4-7 days. Thirteen (10%) patients showed no recovery. The overall mortality was 18 (13.7%) patients. The mean time for ANC recovery seen in hematological malignancies was 6.34 days whereas for solid tumors it was 4.88 days. Patients with ANC <100 cells/mm(3) were more likely to die than patients with ANC >300 cells/mm(3) by a factor of 4.3. Similarly patients >50 years of age were 2.7 times more likely to die than younger patients. CONCLUSION Our study demonstrated that use of GCSF, in addition to intravenous antibiotics, in treatment of patients with chemotherapy induced febrile neutropenia accelerates neutrophil recovery, and shortens antibiotic therapy and hospitalization. We propose to risk classify the patients at the time of admission to evaluate the cost effectiveness of this approach in a resource constrained setup.

Efficacy, Tolerability, and Biomarker Analyses of Once-Every-2-Weeks Cetuximab Plus First-Line FOLFOX or FOLFIRI in Patients With KRAS or All RAS Wild-Type Metastatic Colorectal Cancer: The Phase 2 APEC Study

Micro‐Abstract The nonrandomized phase 2 APEC trial investigated first‐line once‐every‐2‐weeks cetuximab plus chemotherapy (investigators choice of FOLFOX or FOLFIRI) studied patients with KRAS/RAS wild‐type metastatic colorectal cancer. We observed an activity and safety profile similar to that reported in prior first‐line pivotal studies involving weekly cetuximab, suggesting that once‐every‐2‐weeks cetuximab is effective and tolerable as first‐line therapy. Background: In patients with KRAS wild‐type (wt) metastatic colorectal cancer (mCRC), outcomes with first‐line chemotherapies are improved by adding weekly cetuximab. The APEC study investigated first‐line once‐every‐2‐weeks cetuximab plus chemotherapy for patients with KRAS wt mCRC; additional biomarker subgroups were also analyzed. Patients and Methods: APEC was a nonrandomized phase 2 trial conducted in the Asia‐Pacific region. Patients (n = 289) received once‐every‐2‐weeks cetuximab with investigators choice of chemotherapy (FOLFOX or FOLFIRI). The primary end point was best confirmed overall response rate (BORR); progression‐free survival (PFS) and overall survival (OS) were secondary end points. Early tumor shrinkage (ETS) and depth of response (DpR) were also evaluated. Results: In the KRAS wt population, BORR was 58.8%, median PFS 11.1 months, and median OS 26.8 months. Expanded RAS mutational analysis revealed that patients with RAS wt mCRC had better outcomes (BORR = 64.7%; median PFS = 13.0 months; median OS = 28.4 months). The data suggest that ETS and DpR may be associated with survival outcomes in the RAS wt population. Although this study was not designed to formally assess differences in outcome between treatment subgroups, efficacy results appeared similar for patients treated with FOLFOX and FOLFIRI. There were no new safety findings; in particular, grade 3/4 skin reactions were within clinical expectations. Conclusion: The observed activity and safety profile is similar to that reported in prior first‐line pivotal studies involving weekly cetuximab, suggesting once‐every‐2‐weeks cetuximab is effective and tolerable as first‐line therapy and may represent an alternative to weekly administration.

Frequency and Outcome of Graft versus Host Disease after Stem Cell Transplantation: A Six-Year Experience from a Tertiary Care Center in Pakistan

Objective. The objective of this study was to evaluate the frequency and outcome of graft versus host disease after stem cell transplantation for various haematological disorders in Pakistan. Materials and Methods. Pretransplant workup of the patient and donor was performed. Mobilization was done with G-CSF 300 μg twice daily for five day. Standard GvHD prophylaxis was done with methotrexate 15 mg/m2 on day +1 followed by 10 mg/m2 on days +3 and +6 and cyclosporine. Grading was done according to the Glucksberg classification. Results. A total of 153 transplants were done from April 2004 to December 2011. Out of these were allogeneic transplants. There were females and males. The overall frequency of any degree of graft versus host disease was 34%. Acute GvHD was present in patients while had chronic GvHD. Grade II GvHD was present in patients while grade III and IV GvHD was seen in patients each. Acute myeloid leukemia and chronic myeloid leukemia were most commonly associated with GvHD. The mortality in acute and chronic GvHD was 8.8% and 12% respectively. Conclusion. The frequency of graft versus host disease in this study was 34% which is lower compared to international literature. The decreased incidence can be attributed to reduced diversity of histocompatibility antigens in our population.

Successful Engraftment and Survival Following Allogeneic Hematopoietic Stem Cell Transplant in a Child with Familial Hemophagocytic Lymphohistiocytosis

Hemophagocytic syndrome is a rare disorder mainly affecting children. Symptoms include prolonged fever, hepatosplenomegaly and cytopenias. Allogeneic stem cell transplant appears to provide the best overall cure rate in this disease. The authors report a young boy, the second child of consanguineous parents, diagnosed with familial hemophagocytic lymphohistiocytosis (HLH) who underwent allogeneic stem cell transplant form HLA matched father.

Presenting features, treatment patterns and outcomes of patients with breast cancer in Pakistan: Experience at a university hospital

BACKGROUND Breast cancer is the most common cancer in Pakistani women. We report the presenting features, treatment patterns and survival of breast cancer from a University Hospital in Southern Pakistan and compare the data with international population based studies. MATERIALS AND METHODS Medical records of patients diagnosed to have breast cancer between January 1999 and November 2008 were reviewed retrospectively. RESULTS A total of 845 patients were identified. Median age of diagnosis was 48 years (range 18-92). Clinical stage was as follows: Stage I 9.9%; Stage II 48.5%; Stage III 26.2%; Stage IV 13.8%; data not available 1.5%. Approximately, half (51.6%) were estrogen receptor (ER) positive and 17.5% over-expressed Her2/neu. Nearly 23% patients received neo-adjuvant chemotherapy while 68.9% received adjuvant chemotherapy. Anthracycline based treatment was the most common treatment until 2003 while later on, patients also received taxanes and trastuzumab based therapy. Age, stage, tumor size, lymph node status, tumor grade, ER status, treatment with hormonal therapy and radiation were the major predictive factors for overall survival (OS). We report an impressive 5 year OS of 75%, stage specific survival was 100%, 88% and 58% for Stages I, II and III respectively. CONCLUSION The majority of patients present at a younger age and with locally advanced disease. However, short term follow-up reveals that the outcomes are comparable with the published literature from developed countries. Long-term follow-up and inclusion of data from population-based registries are required for accurate comparison.