Safety and efficacy of bendamustine in the conditioning regimen for autologous stem cell transplantation in patients with relapsed/refractory lymphoma

BACKGROUND: Bendamustine is an attractive option for the management of both de novo and relapsed lymphomas. It is being increasingly used in the conditioning regimen for autologous stem cell transplantation (SCT) and can be an alternative to the traditionally-used carmustine. In this study, we aimed to determine the safety and efficacy of bendamustine in the conditioning regimen for autologous SCT in refractory/relapsed lymphomas. METHODS: We designed a descriptive study to evaluate bendamustine in combination with etoposide, cytarabine, and melphalan (BeEAM) in the conditioning regimen for autologous SCT. RESULTS: Fourteen patients (median age, 28 yr) with Hodgkin's lymphoma (HL) (N=8), non-Hodgkin's lymphomas (NHL) (N=5), or peripheral T-cell lymphoma, not otherwise specified (PTCL NOS) (N=1) were included in the study. A median number of 5.95×10⁶ CD34+ cells/kg were transfused. Median times to absolute neutrophil count and platelet engraftment were 17 days and 24 days, respectively. The 100-day transplantation mortality rate was 28% (4 patients). Eight patients (57.14%) had GII-III acute kidney injury, four patients (28.5%) had GIII-IV hyperbilirubinemia, and twelve patients (85%) had GII-III diarrhea. After 3 months, 37% (5 patients) and 21.4% (3 patients) demonstrated complete response and partial response, respectively. The median follow-up was 5.5 months (15 days–19 mo). At the final follow-up, 7 patients (50%) were alive and in CR. CONCLUSION: Our study showed that bendamustine is a potentially toxic agent in the conditioning regimen for autologous SCT, resulting in significant liver, kidney, and gastrointestinal toxicity. Further studies are required to assess its safety and efficacy at reduced doses.

Cost and quality issues in establishing hematopoietic cell transplant program in developing countries

The hematopoietic cell transplant [HCT] activity has grown significantly over the past two decades in both developing and developed countries. Many challenges arise in establishing new HCT programs in developing countries, due to scarcity of resources and manpower in expertise in HCT. While cost issues can potentially hinder establishment of new HCT programs in certain regions, the focus on quality and value should be included in the general vision of leadership before establishing an HCT program. The main challenge in most developing countries is the lack of trained/qualified personnel, enormous start-up costs for a tertiary care center, and quality maintenance. Herein, we discuss the main challenges from a cost and quality perspective which occur at initiation of a new HCT program. We give real world examples of two developing countries that have recently started new HCT programs despite significant financial constraints. We also portray recommendations from the Worldwide Network of Blood and Marrow Transplantation for levels of requirements for a new HCT program. We hope that this review will serve as a general guide for new transplant program leadership with respect to the concerns of balancing high quality with concurrently lowering costs

Chromosomal abnormalities in primary myelodysplastic syndrome

To determine the frequency of cytogenetic abnormalities in patients diagnosed as primary myelodysplastic syndrome [MDS] using conventional karyotyping. Case series. The Clinical Laboratory. The Aga Khan University Hospital, Karachi, between January 2006 - June 2012. Patients of all ages and either gender who fulfilled WHO criteria for MDS were included. Cytogenetic analysis was conducted at the time of diagnosis. Patients who had secondary MDS were excluded from analysis. Chromosome identification and karyotype description was done according to the International System for Chromosome Nomenclature [ISCN, 1995] and described as frequency percentage. Out of the 122 cases of MDS, 71 patients had their karyotype done at the time of diagnosis, including 42 males [59.2%] and 29 females [40.8%] with median age of 60 years. Forty one [57.7%] showed normal karyotype and 30 [42.3%] showed clonal karyotypic abnormalities at diagnosis. Out of which 14 [19.7%] had single, 11 [15.5%] had complex and 6 [8.5%] had double cytogenetic abnormalities. The common abnormalities found were: trisomy 8 in 7 cases [9.9%], -7/del [7q] in 3 cases [4.2%], -Y and complex 5q in 2 cases [2.8%] each, complex trisomy 8, del 11q, inversion 9, trisomy 19 and del 20q were found in 1 case [1.4%] each. Other abnormalities were found in 11 cases [15.5%]. Trisomy 8 was the most common disorder/abnormality found in this study population followed by the complex cytogenetics

Aplastic anemia: clinicohaematological features, treatment and outcome analysis

To determine the clinicohaematological features, treatment and outcome of children diagnosed with aplastic anemia at a single institution. Observational study. The Aga Khan University Hospital, Karachi, from January 1999 till December 2008. Medical records of children aged less than 15 years of age diagnosed with aplastic anemia were reviewed. Clinicohaematological features, treatment and its response to therapy and outcome were recorded. Results were described in percentages. Ninety patients were diagnosed to have aplastic anemia [AA]; 65 were male during the study period. Age ranged from 1 to 15 years. Fever in 65 patients [72.2%], pallor in 53 [58.8%], skin bleeding in 49 [54.4%] and epistaxis in 31[34.4%] were the most common and frequent presenting features. Congenital [Fanconi's] anemia was found in 15 [16.6%] and acquired idiopathic in 75 [83.4%] of patients. Very severe aplastic anemia [VSAA] was seen in 29 [32.2%], 26 [28.9%] had severe AA and 17 [18.9%] had moderate AA. Eight patients [8.9%] underwent haematopoietic stem cell transplantation [HSCT], 12 [13.3%] received immunosuppressive therapy [IST] and 70 patients [77.7%] received other and supportive therapy. Five [62.5%] patients showed complete response to HSCT and 3 [37.5%] failed to engraft. IST showed complete response in 3 [25%], partial response in 5 [41.6%] and no response in 4 [33.3%]. Twenty two patients [24.4%] expired either due to infection in 16 [72.7%, fungal in 6, bacterial in 10] and intracranial haemorrhage in 6 [27.3%] cases. Majority of cases with AA were acquired and idiopathic in etiology. VSAA and SAA were frequent. Response to HSCT and IST was sub-optimal

Additional chromosomal abnormalities in Philadelphia-positive chronic myeloid leukemia

The emergence of non-random chromosomal abnormalities is a well-recognized occurrence in chronic myeloid leukemia [CML] and detection of these abnormalities is important in prognostic stratification. The frequency and types of additional chromosomal abnormalities in CML patients has not been determined in our region. We conducted a descriptive, prospective study of additional chromosomal abnormalities in patients with an established diagnosis of Philadelphia-positive CML from May 2001 to June 2007. Cytogenetic studies were repeated every three months with the conventional G-banding technique and described according to the international system for Human Cytogenetic Nomenclature. All patients received imatinib mesylate. In 219 patients with Philadelphia-positive CML, 34 [15.5%] [median age, 38 years] developed 51 additional chromosomal abnormalities. Five cases had variant translocations prior to starting imatinib; the remaining 29 cases acquired chromosomal abnormalities after starting imatinib, including 8 cases that received prior interferon-alfa. Twenty-one patients were in chronic phase, 10 in accelerated phase and 3 were in blast crisis. Trisomy 8 was the most frequent abnormality followed by random chromosomal abnormalities and variants of the Philadelphia chromosome. The overall frequency of additional chromosomal abnormalities was similar to that in previous reports. Early identification of these abnormalities may help in adapting to a more appropriate therapeutic approach

Diagnostic tool for glanzmann's thrombasthenia clinicopthologic spectrum

To platelet aggregometry and describe the clinical spectrum of Glanzmann`s thrombasthenia diagnosed by platelet aggregometry. A case-series. This study was carried out at the clinical laboratories at the Aga Khan University Hospital, Karachi from January 2003 to January 2006. All patients irrespective of age and gender presenting with bleeding symptoms and having normal platelet count were evaluated. Demographic details, relevant clinical history along with results of complete blood count, bleeding time and platelet aggregation studies were retrieved through computerized data base and evaluated for the diagnosis of Glanzmann`s thrombasthenia. During the study period, 50 out of 2317 patients [2.2%] were diagnosed as Glanzmann`s thrombasthenia by platelet aggregometry with male to female ratio of 0.85:1 and median age of 10.2 years [ranging from 3 months to 27 years]. Common symptoms were epistaxis, oral and gingival bleed, bleeding from minor cuts and trauma that were observed in 46% of the patients; while 18%, 8% and 10% of them also complained of bruising, hematuria and bleeding per rectum respectively. Majority i.e. 86% had a bleeding time greater than 10 minutes. All patients had received blood or blood products for their bleeding episodes. Platelet aggregometry is a useful diagnostic modality for the assessment of Glanzmann`s thrombasthenia. The disorder presents with muco-cutanoeus bleeding and was found to be a common cause of bleeding in our setup

Frequency of hypercalcemia in patients of multiple myeloma in Karachi

To determine the frequency of hypercalcemia and skeletal abnormalities in multiple myeloma patients. Cross-sectional study. Study was conducted from January 1999 to July 2004 at the Aga Khan University Hospital [AKUH], a tertiary care hospital in Karachi, Pakistan. Medical records of all the diagnosed cases of multiple myeloma at their presentation to hospital were reviewed. The frequency of hypercalcemia and skeletal lesions was calculated. Independent sample test and chi-square test as appropriate, was applied to calculate the difference in parameters between normocalcemic and hypercalcemic patients. Sixty-seven percent patients were males and 33% were females. The mean age was 61 +/- 11 years. Of the 105 study patients, 51.2% had hypercalcemia [S.Ca >2.64 mmol/l]. Radiological survey showed different levels of skeletal involvement in 89.8% of patients. It was also found that 94.3% of hypercalcemic patients had skeletal lesions, out of which 20% had advanced [stage 3] bone lesions. Also noteworthy was the fact that 84.6% of normocalcemic patients had mild /moderate [stage 1 and 2] skeletal lesions. There was higher frequency of hypercalcemia in multiple myeloma patients in this series. Skeletal lesions were present in significant number of these patients. It is suggested that patients with multiple myeloma should be checked for serum corrected calcium and radiological surveys be included in routine workup for early detection and prevention of hypercalcemia and skeletal lesions