Real-World Outcomes in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma Treated With Bortezomib/Cyclophosphamide/Dexamethasone and Bortezomib/Lenalidomide/Dexamethasone as Upfront Treatment.

Introduction Multiple myeloma (MM) is a hematological disorder characterized by aberrant multiplication of malignant plasma cells in the bone marrow. The current mainstay of treatment for patients with newly diagnosed MM (NDMM) is a triplet regimen with a proteasome inhibitor, immunomodulatory imide, and dexamethasone. The two most common of these triplet regimens are VLD (bortezomib/lenalidomide/dexamethasone) and VCD (bortezomib/cyclophosphamide/dexamethasone). This study aims to compare the outcomes between these two therapies in transplant-ineligible patients with NDMM. Methods We conducted a retrospective study at the Aga Khan University Hospital in Karachi, Pakistan. All NDMM transplant-ineligible patients either receiving VLD or VCD therapy between January 2015 and December 2022 were included in our study. Hematological parameters before and after treatment were obtained from hospital records. Response to treatment was classified according to the International Myeloma Working Group (IMWG) response criteria as either complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD), or progressive disease (PD). The response to treatment as well as overall survival (OS) and progression-free survival (PFS) was compared between VCD and VLD therapy. A p-value of 0.05 or less was taken to be statistically significant. Results Twenty (23.8%) patients in the VCD group and 20 (23.0%) in the VLD group underwent complete remission. Seven (8.3%) patients experienced disease progression in the VCD group, while the figure stood at three (3.4%) in the VLD group. There was no statistically significant difference in the overall response rate between the VCD (58; 69.0%) and VLD (70; 80.5%) groups (p=0.086), a difference that was not statistically significant on the Chi-square test. OS was comparable between VCD (69.1 months, 95%CI: 61.3-77.0) and VLD (76.9 months, 95%CI: 69.0-85.0) therapies. Conclusions The study did not identify any statistically significant distinction in the treatment outcomes between the VCD and VLD regimens among NDMM patients ineligible for transplantation. Nevertheless, the study highlights the positive outcomes observed with both treatments in this specific patient cohort. This implies that either regimen could be deemed suitable as a treatment option for patients in low- and middle-income countries. Since both regimens demonstrate comparable effectiveness, assessing the cost-effectiveness of these regimens is crucial. Future research should also explore the economic aspects of the two treatment options.

Burden of Cardiac Siderosis in a Thalassemia-Major Endemic Population: A Preliminary Report From Pakistan.

OBJECTIVE: To describe the initial experience and demographics of T2* cardiac magnetic resonance-based myocardial-iron quantification of transfusion-dependent thalassemia-major (TM) patients from Pakistan and the correlation with serum ferritin. METHODS: Eligible TM patients presenting between April 2014 and April 2015 to Aga Khan University Hospital, Pakistan, for T2*CMR were included. The severity of myocardial-iron deposition was defined as follows: normal T2*>20 ms, mild-moderate T2*10 to 20 ms, and severe T2*<10 ms. Cardiac symptoms were classified using the NYHA functional classification. Echocardiographic systolic and diastolic functions were performed. Continuous variables were presented as the median (minimum-maximum value). Correlation was measured using the Spearman rank correlation. Multivariate logistic regression was used to determine factors associated with the NYHA functional class. RESULTS: A total of 83 patients (49 male and 34 female) with TM, age 19 (5 to 45) years at presentation for T2*CMR, were reviewed. At presentation, 70% of the patients were classified as NYHA class II or worse. T2*<20 ms was observed in 62.6% of the patients, with 47% showing severe iron deposition (T2<10 ms). No correlation of T2*<20 ms (r=-0.157, P=0.302) and T2*<10 ms (r=-0.128, P=0.464) was observed with serum ferritin. On multivariate analysis, lower T2* values correlated with a worsening NYHA functional class. CONCLUSIONS: There is a high prevalence of severe myocardial iron load in Pakistani TM patients. Serum ferritin did not correlate with T2* values. Lower T2* was the only clinical factor associated with the NYHA functional class.

Recurrent spontaneous splenic rupture in a patient with congenital factor XIII deficiency.

We describe an unusual presentation of factor XIII (FXIII) deficiency in a 17-year-old boy who was diagnosed with this congenital deficiency at the age of 18 months. He had a history of spontaneous splenic rupture 8 years ago, which was managed conservatively. He now presented with sudden severe abdominal and left shoulder pain for 1 day, with no history of antecedent trauma. He was in shock, and examination revealed diffuse peritonitis. A computed tomography scan showed a grade IV splenic laceration. He was taken as an emergency to the operating room where he was found to have a shattered spleen, and a splenectomy was performed. He received cryoprecipitate transfusions perioperatively. After an uneventful recovery, the patient was discharged. To the best of our knowledge, this is the first described case of a recurrent splenic rupture in a patient with FXIII deficiency.

Endocrine complications in patients of beta thalassemia major in a tertiary care hospital in Pakistan.

OBJECTIVE: To determine the major endocrine complications present in patients of Thalassemia major presenting to a tertiary care center in Karachi, Pakistan. METHODS: Records of all thallasemia major patients at a Haematology Department in a tertiary care hospital of Karachi were retrospectively reviewed from May to August 2009 with specific focus on endocrine data and investigations. The patients' data was recorded in a questionnaire and analyzed using SPSS v.17, frequencies and percentages along with corresponding 95% confidence interval were computed. RESULTS: Our data revealed that a significantly small percentage of those under care received regular endocrine follow-up. Male hypo-gonadal abnormalities had the highest probability; 100% of the tested patients had decreased levels of testosterone, while 95.2% had raised serum creatinine levels. Parathyroid dysfunction was noted in 40% of the patients. Of those screened 29.4% had blood glucose levels in the diabetic range and 11.8% of the tested patients had reduced levels of FT4. CONCLUSION: A high frequency at endocrine dysfunctions seen in thalasaemia patients included: male hypogonadism, parathyroid dysfunction, deranged blood glucose and FT4 levies.

Clinico-pathologic features of chronic myeloid leukemia and risk stratification according to Sokal score.

OBJECTIVE: To compile the clinical and haematological parameters of chronic myeloid leukemia (CML) and risk stratification according to Sokal score in our population. DESIGN: A descriptive analysis. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, during the period from August 1997 to August 2005. SUBJECTS AND METHODS: All patients with diagnosis of chronic myeloid leukemia treated as outpatient in haematology clinic, or admitted in haem-oncology wards in The Aga Khan University Hospital were included. Records were retrospectively analyzed for clinicopathologic features. Risk groups were assigned as per Sokal scoring. RESULTS: During the 8 years study period, 245 patients with chronic myeloid leukemia were analyzed, the median age of presentation was 35 years (range 11-73); with male to female ratio 1.69:1. At the time of diagnosis, 178 patients (72.6%), 48 (19.7%) and 17 (7.8%) of patients were in chronic, accelerated and blast phase of the disease respectively. Abdominal fullness was the frequent clinical presentation followed by fever. Laboratory parameters revealed mean hemoglobin 10.0 g/dl (range 4.6-15), mean total leukocyte count 168 x 10(9)/L (35-959) and mean platelets 408 x 10(9)/L (range 30-2335). The mean size of spleen at the time of presentation was 9.2 cm below the left subcostal margin. A large number of patients (46.2%) were in high risk group according to Sokal score i.e. > 1.2. CONCLUSION: CML occurred more commonly at younger age in this series. Most of these patients were in high risk group according to Sokal score.

Role of ICT malaria immunochromatographic test for rapid diagnosis of malaria.

OBJECTIVE: To evaluate the sensitivity and specificity of immunochromatographic test (ICT) malaria p.f/p.v using microscopy as the gold standard diagnosis. METHODS: Five hundred and sixty patients of both sexes and all age groups with clinical suspicion of malaria were studied. Venous blood was collected for microscopy and ICT. Thick and thin films prepared and stained with Leishman's stain were examined. ICT malaria test was performed and interpreted according to manufacturer's instructions. Data was analyzed using Epi-6. RESULTS: A total of 560 cases were studied, 339 males and 221 females with age ranges between 2 to 73 years. Seventy two (12.85%) cases had parasitaemia (with or without sexual forms). On microscopy 65 (11.6%) cases had asexual-stage parasitaemia and 7 (1.25%) cases had P. falciparum gametocytes only. Thirty two cases were infected with P. falciparum, 29 with P. vivax and 4 had mixed infection. For P. falciparum the ICT was 97.0% sensitive, 98.3% specific, with positive predictive value (PPV) of 78.0% and a negative predictive value (NPV) of 99.8%. For P. vivax the sensitivity was only 89.7%, specificity 97.9%, PPV was 70.3% and NPV 99.4%. CONCLUSION: Our results are in concordance with previous studies. Rapid tests though expensive are simple to perform and effective diagnostic tools of malaria. They can be used selectively, though microscopy remains the gold standard diagnosis, economical and accurate if performed by skilled technologists.

Significance of cytogenetic abnormalities in acute myeloid leukaemia.

OBJECTIVE: To evaluate the role of karyotype in acute myeloid leukaemia (AML) as a predictor of response to induction chemotherapy. METHODS: A cross-sectional study was carried out at the department of Pathology and Oncology, Aga Khan University Karachi from January 2003 to January 2005. Newly diagnosed patients with denovo AML admitted to the hospital were included in the study. Diagnosis of AML was based on FAB criteria, immunophenotyping and cytogenetic studies. They were treated according to standard protocols (combination of anthracycline and cytarabine -3+7) and those who had acute promyelocytic leukaemia additionally received all- trans retinoic acid (ATRA). RESULTS: A total of 56 patients were enrolled, 4 were excluded due to inadequate cytogenetic analysis and the remaining patients entered the study protocol. There were 32 males and 20 females with mean age of 31.3 years (range 9 months to 73 years). Thirty-five (67.3%) patients had normal karyotype while 17 (32.7%) were found to have cytogenetic abnormalities. Eleven patients did not receive treatment at our hospital. Half of the (51.2%) patients out of remaining 41 achieved complete remission on bone marrow examination after receiving induction chemotherapy. In favourable risk group 3/3 (100%) achieved complete remission (CR) while 15/32 (46.9%) in intermediate risk group and 3/6 (50%) in unfavourable risk group. There was low CR rate in patients with high white cell counts. CONCLUSION: The frequency of cytogenetic abnormalities in AML and response to induction chemotherapy was low when compared with international data possibly due to the small sample size. However, there was a clear difference in CR rates between favourable and unfavourable risk groups.

Hairy cell leukemia: clinical presentation and long term follow up after treatment with 2-chlorodeoxyadenosine (2-CdA).

The aim of the study was to the clinical features and long term follow up after treatment with Cladarbine in a tertiary care hospital. Seven patients with hairy cell leukemia were diagnosed between January 1990 till December 2003. Diagnosis in all the patients was established by bone marrow aspirates and trephine biopsy along with TRAP. In two patients the diagnosis was supplemented by flowcytometry and in another two patients by splenectomy. Six patients were male while one was female. Mean age was 47.7 years (range 36-64). Most common presenting features were pallor and weakness (n=5). All patients had splenomegaly. Blood count at presentation revealed that one patient had bicytopenia, two had isolated thrombocytopenia, and three had pancytopenia. Treatment responses were evaluable in seven patients. Complete response was seen in six patients (85.7%). One patient died after two months due to sepsis while 3 (50%) patients relapsed. Those who relapsed received another course of CDA and have maintained remission with a median duration of response of 48 months (20-48). From this small series we can conclude that CDA is an effective treatment for HCL and even it works very well in relapsed cases.

Anaphylactic reaction after intramuscular injection of cyanocobalamin (vitamin B12): a case report.

We report a case of anaphylactic reaction to intramuscular injection of cyanocobalamin. This 52-year-old lady was diagnosed as a case of megaloblastic anemia secondary to dietary vitamin B12 deficiency. She had severe anaphylactic reaction after the parenteral administration of cyanocobalamine. Later she received oral vitamin B12 with no adverse effects. The purpose of this case report is to draw attention to the hypersensitive reaction to injectable vitamin B12, which is rarely seen. This could be due to sensitization to the vitamin B12 molecule itself or an IgE mediated reaction. We concluded that anaphylactic reaction to vitamin B12 is a rare but serious side effect and it should be kept in mind while the drug is being administered to the patient, especially via the parenteral route.

Frequency of irregular red cell alloantibodies in patients with thalassemia major: a bicenter study.

OBJECTIVE: To provide frequency and distribution pattern of various types of irregular red cell alloantibodies in patients with thalassemia major. METHODS: This is a descriptive study conducted at two centers from January to December 2001. Purposive sampling was done and all patients diagnosed to have thalassemia major were included in the study. Antibody identification was carried out on serum employing commercial two-cell panel using standardized blood bank methods. If patients were found to have an irregular red cell alloantibody then the antibody identification was performed using 16 panel cells. RESULTS: A total of ninety-seven patients were included in the study. Fifty-three patients were males and 44 females. Mean age was 10.6 years. Irregular red cell alloantibodies were found in 9 (9.2%). Mean age of patients who developed red cell alloantibody was 11.9 years. Three (33.3%) patients developed anti-K while two (22.2%) had non-specific antibody. One patient each developed anti-D (11.1%) and anti-E (11.1%). Two had anti-D (11.1%) and anti-C while the other one (11.1%) developed anti-E and anti-K. CONCLUSION: We concluded that there is relatively high rate of alloimmunization in our set of patients when compared to data from our region. We also suggest that red cell alloimmunization should not be overlooked in patients receiving regular blood transfusions.