A Deeper Depth of Response After Salvage Therapy Improves Outcomes of Autologous Stem Cell Transplantation in Relapsed Lymphoma and the Feasibility of Non-controlled Rate Freezing of Peripheral Blood Stem Cells.

Background High-dose chemotherapy followed by autologous stem cell transplantation is considered a standard treatment approach for patients with relapsed Hodgkin's lymphoma (HL) and non-Hodgkin lymphoma (NHL). The goal of autologous stem cell transplant in relapsed lymphoma is to achieve long-term disease control, i.e., cure, in contrast to disorders like multiple myeloma, where it only prolongs the duration of remission, progression-free survival, and improves the quality of life. Published outcomes of high-dose therapy and ASCT and the impact of different factors affecting survival in low- to middle-income countries are very limited. Our study analyzed all the autologous stem cell transplants performed in our center over a six-year period to ascertain engraftment, responses, outcomes, and variables that may have impacted transplant outcomes. Methods We conducted a retrospective study including 76 patients from January 2015 to December 2020. Data were retrieved from electronic medical records at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Results Out of a total of 82 autologous transplant patients, 76 were eligible for the study, out of which 50 (66%) had HL and 26 (34%) had NHL. The median age was 29 years (range 18-53) and 29 years (range 20-45) for HL and NHL, respectively. The male-to-female ratio was 5:2 and 4:1 for HL and NHL, respectively. The majority had advanced-stage disease, 85% in HL and 75% in NHL. The minimum cell dose infused was 2.5 million CD34+ cells/kg. Median days to platelets and ANC engraftment were 14 and 11 days, respectively. The 30-day transplant-related mortality was 8.9% and 7.4% in HL and NHL, respectively. The 100-day mortality was 15.2% and 11% in HL and NHL, respectively. The two-year disease-free survival (DFS) and overall survival (OS) were 83% and 83%, respectively, in HL patients. The two-year DFS and OS were 78% and 85%, respectively, in NHL patients. Conclusion High-dose therapy and autologous stem cell transplantation in low- to middle-income countries are limited to relatively younger patients, potentially curative conditions such as lymphoma, and predominantly after achieving a complete response to salvage therapy due to limited resources. Due to these factors, our study shows excellent response rates and survival outcomes compared to internationally published data. Engraftment was also excellent and comparable to published data despite the non-controlled rate freezing of peripheral blood stem cells.

Management of Acute Lymphoblastic Leukemia During Pregnancy: A Case Report and Review of the Literature.

Acute lymphoblastic leukemia (ALL) during pregnancy necessitates treatment with high-dose chemotherapy, which can threaten the lives of both the mother and fetus. The aim of the treatment not only focuses on selecting and administering optimal chemotherapy with appropriate doses to the mother but also reflects the crucial understanding of the fetal gestational age at the time of administration of chemotherapy to minimize fetal exposure. We describe the case of a 19-year-old patient diagnosed with ALL at 29 weeks gestation. She received treatment in the third trimester with the Berlin-Frankfurt-Munster (BFM) 2000 induction chemotherapy protocol consisting of a combination of daunorubicin, vincristine, pegaspargase, prednisolone, and intrathecal (IT) methotrexate and gave birth to a healthy baby girl via vaginal delivery four weeks after initiating the induction of chemotherapy.

Developing an Allogeneic Hematopoietic Progenitor Cell Transplant Service in a Resource-Limited Country: Challenges and Outcomes.

Introduction Allogeneic stem cell transplant has curative potential for many hematological disorders. Building an allogeneic hematopoietic progenitor cell transplant (HPCT) unit requires huge investment, infrastructure, equipment, medical supplies, and training of health care professionals. The key objective of this study is to share our experience of developing an allogeneic HPCT service at our tertiary care cancer hospital in a low-middle-income country. In addition, this study presents the outcomes of the first 30 allogeneic HPCTs done at our center. Methods This retrospective observational study included adult patients 18 years old or older with hematological malignancies who underwent allogeneic HPCT between July 2019 and April 2023 at Shaukat Khanum Memorial Cancer Hospital and Research Centre. Result Of the 30 patients, 24 underwent matched sibling donor (MSD) transplants in which a myeloablative-conditioning regimen (MAC) was used in 19, and a reduced conditioning regimen (RIC) was used in one. Of the six haploidentical-related donor transplants, four received MAC, and two received RIC. The median recipient age at HPCT was 23 and 21 years for MSD and Haplo-related donor transplants, respectively. The median follow-up duration was 12 months (Range: 10 days - 33 months). The overall survival rate at one year was 71.3% among all allogeneic stem cell transplant patients, whereas the disease-free survival rate at one year was 63.7%. In the acute lymphoblastic leukemia group, the disease-free survival rate at one year post allograft was 51.5%, while in the acute myeloid leukemia group, it was 78.7%. Conclusion This study demonstrates the successful development of an allogeneic bone marrow transplant unit at our hospital despite significant financial constraints. This has allowed us to provide a potentially curative and life-saving treatment to a substantial number of cancer patients. The bone marrow transplant outcomes of this study are comparable to those reported by international bone marrow transplant registries.

Bleomycin-Induced Fulminant Hyperpyrexia: A Report of Two Cases and Review of Literature.

Bleomycin is a commonly used cytotoxic agent that has proven its efficacy over the years. Though a common part of many protocols targeting lymphomas and germ cell tumors, it does have some serious adverse effects. Bleomycin is notorious for pulmonary toxicity and very rarely may cause fulminant hyperpyrexia. We describe two cases of classical Hodgkin's lymphoma (cHL) developing acute fulminant hyperpyrexia after administration of the first dose of bleomycin as part of chemotherapy protocol. This is a rare adverse reaction that closely mimics anaphylaxis and has an unpredictable and possibly fatal course. Health care professionals involved in the administration of chemotherapy need to be very vigilant in monitoring for symptoms of this reaction.

Cytomegalovirus Reactivation in Patients With Acute Lymphoblastic Leukemia in Non-transplant Setting.

Acute lymphoblastic leukemia is predominately a childhood disease and around two third of cases are of B-cell phenotype. Cytomegalovirus is an important cause of morbidity and mortality in allogeneic hematopoietic progenitor cell transplant; however, it is rare in patients with B-cell acute lymphoblastic leukemia in non-transplant settings. In this study, we evaluated 72 patients of acute precursor (pre) B-cell acute lymphoblastic leukemia at Shaukat Khanum Memorial Cancer Hospital and Research Center, out of which three were positive for Cytomegalovirus.

Outcomes of Philadelphia Positive Acute Lymphoblastic Leukemia in Adolescent and Young Adults.

Background Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) accounts for 25% of acute lymphoblastic leukemia cases in the adolescent and young adult (AYA) age subgroup. It is associated with poor outcomes and is considered a standard indication for allogeneic stem cell transplant (Allo-SCT). Improved outcomes have been reported with addition of tyrosine kinase inhibitors (TKIs) to chemotherapy in children and the role of Allo-SCT is now being debated in the first remission. Complete response (CR) at three months is associated with improved survival even without Allo-SCT in first CR. In this study, we have analyzed disease-free survival (DFS), overall survival (OS), and factors affecting survival outcomes of Ph+ ALL in the AYA subgroup, in resource-limited settings treated with chemotherapy and TKIs. Materials and methods This is a retrospective, multicenter cohort study of Ph+ ALL AYA patients, aged 18-40 years, and registered between January 2015 and December 2020. Primary objectives are to calculate disease-free survival (DFS) and overall survival (OS). Secondary objectives are to identify prognostic factors affecting response rates and outcomes. List of cases was obtained from hospital information system (HIS) and data were collected from patient case notes and electronic medical records. Data analysis was done utilizing the SPSS statistical program (Armonk, NY: IBM Corp.). Results Forty-nine patients were identified with Ph+ ALL with a median age of 23 years (range: 18-40 years) and a male-to-female ratio of 2.5:1. None of the patients had central nervous system (CNS) disease. White cell count was >30,000 per mm3 in 26% of patients, while 13% had additional cytogenetic abnormalities. Thirty-three percent patients received adult (hyper-cyclophosphamide, vincristine, Adriamycin, and dexamethasone {CVAD}) protocols while 67% received pediatric-inspired (Berlin-Frankfurt-Munster {BFM} 2000 or UK-ALL 2003/2011) protocols. TKI therapy was received by 66% of patients during treatment (early: 37%; late: 29%) and 34% did not receive TKIs due to financial constraints. CR after induction was achieved in 69% cases. Induction mortality was 16%. The median DFS for the entire cohort was 27 months (0.93-53.06) and the median OS was 29 months (8.89-49.10). The median OS in Allo-SCT group was not reached vs 8.0±8.8 months (p=0.05) with chemotherapy only. The OS was significantly better in patients with no additional cytogenetic abnormalities, pediatric-inspired chemotherapy protocols, early use of TKIs in induction phase, Allo-SCT, and post-Allo-SCT use of TKIs. Conclusion Addition of TKIs to pediatric-inspired chemotherapy protocols in Ph+ ALL AYA patients and Allo-SCT results in better overall survival. TKI availability remains a significant issue in low-income countries due to significant financial burden on the patients. Allo-SCT continues to be an attractive option, particularly in low-income countries providing an option for cure in Ph+ ALL.

Outcomes of Diffuse Large B-Cell Non-Hodgkin's Lymphoma After Gemcitabine-Based Second Salvage Chemotherapy: A Single-Center Study.

Background Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma with a five-year survival of 60%-70% with chemoimmunotherapy consisting of the R-CHOP combination (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone), with a relapse/refractory rate of 20-50%. Salvage therapy with HDT-ASCT is the treatment of choice for patients with relapsed/refractory disease with a success rate of 50%-60%. Patients who do not respond to the first salvage regimen or who relapsed after the first salvage regimen, with or without high-dose chemotherapy (HDT)-autologous stem cell transplantation (ASCT), have poor overall responses and survival and should be offered novel therapies. The objective of our study was to evaluate responses to second salvage, gemcitabine-based therapy with or without HDT-ASCT in a resource-limited setting. Materials and methods This was a retrospective study, including 55 patients aged >18 years, diagnosed with DLBCL and having received gemcitabine-based second salvage chemotherapy. Results The median age was 34 years, only one patient achieved progression-free survival (PFS) of >12 months with ORR of 27% to two cycles of gemcitabine-based combination, two years PFS and OS of 9.6% and 34%, respectively, and a median PFS and OS of four months and 13 months, respectively. Conclusion DLBCL patients, refractory to first-line and first salvage chemotherapy, should be considered for novel therapies or opt for palliative care rather than second salvage chemotherapy and HDT-ASCT, which results in poor overall response and significant toxicities.

Impact of critical care reconfiguration and track-and-trigger outreach team intervention on outcomes of haematology patients requiring intensive care admission.

Patients with haematological disorders have previously been considered to have poor outcomes following admission to intensive care units. Although a number of haematology centres from outside the UK have now demonstrated improved outcomes, the continuing perception of poor outcomes in this patient group continues to adversely affect their chances of being admitted to some intensive care units (ICUs). Over the past 10 years, there have been many advances within the disciplines of both haematology and intensive care medicine. This study was done to assess outcomes and the impact of an early warning scoring system (EWS) and early involvement of ICU outreach teams. One hundred five haematology patients (haematopoietic stem cell transplant (HSCT) or non-HSCT) had 114 admissions to ICU between April 2006 and August 2008 which coincided with hospital-wide implementation of EWS. The survival to ICU discharge was 56 (53%). Thirty-three (33%) patients were alive at 6 months giving a 1-year survival of 31%. Of the 39 HSCT patients, nine were post-autologous and 30 post-allogeneic transplant. The survival to ICU discharge was 22 (56%) with 14 (36%) patients alive at 6 months. One year survival was 36%. Prior to the introduction of EWS and critical care outreach team (2004), survival to ICU discharge was 44% which has increased to 53% (2006-2008). This is despite an increase in mechanical ventilation in 2006-2008 (50%) as compared to 2004 (32%).The improvement in ICU survivorship was even more prominent in HSCT patients (37% in 2004 versus 56% in 2006-2008). There was a trend towards decreasing Acute Physiology and Chronic Health Evaluation scores with time, suggesting appropriate patients being identified earlier and having timely escalation of their treatment.

Novel use of a peripheral, self-expanding nitinol stent in adjunct to excimer laser coronary atherectomy in the treatment of degenerated vein graft disease.

Decades of successful surgical revascularization of coronary artery disease have led to a growing population with saphenous vein graft disease. However, the treatment of degenerated saphenous vein graft still remains controversial. We report a novel but successful use of a peripheral, self-expanding nitinol stent in adjunct to excimer laser coronary atherectomy (ELCA) in the treatment of symptomatic, degenerated saphenous vein graft disease. The procedure was tolerated well without any short- or long-term complications. The case report is followed by a review of the literature on the treatment of vein graft disease.

Plasma homocysteine levels and the left ventricular systolic function in coronary artery disease patients.

BACKGROUND: Numerous studies have shown a relationship between hyperhomocysteinemia, atherothrombosis and cardiovascular mortality. However, an association between hyperhomocysteinemia and the extent of coronary artery disease (CAD) remains controversial whereas its relationship with left ventricular systolic function has not been established. METHODS: One hundred and fifty-seven patients with angiographically defined CAD were included. The relationships between hyperhomocysteinemia, severity of CAD and left ventricular systolic function were studied. Left ventricular systolic function was determined primarily by ventriculography. The severity of CAD was determined through coronary angiography using the Gensini score and the number of vessels with > or = 50% stenosis. RESULTS: The mean fasting plasma homocysteine level was 13.4 mumol/l+/-0.5 SE. Elevated levels of homocysteine correlated significantly with increased severity of CAD both by the Gensini scores (r-value = 0.344, P < 0.0005) and the total number of diseased vessels (r-value = 0.387, P < 0.0005). The patients with hyperhomocysteinemia were found to have significantly reduced left ventricular ejection fraction (r-value = -0.382, P < 0.0005). A multivariate regression analysis revealed homocysteine level to be an independent predictor of left ventricular systolic function. In addition, adjusted analysis revealed hyperhomocysteinemia to be associated with global left ventricular dysfunction. CONCLUSION: In patients with CAD, homocysteine levels correlate independently with left ventricular systolic function. The mechanism of this association between homocysteine and left ventricular systolic function is unknown but may be due to a direct effect of homocysteine on myocardial function separate from its effects on coronary atherosclerosis.

Current advances in the diagnosis and treatment of renal artery stenosis.

Renal artery stenosis (RAS) is a common condition associated with hypertension and renal insufficiency. The high prevalence of RAS patients with coronary and lower extremity vascular disease has been well established. Fibromuscular dysplasia in young females and atherosclerosis in patients over the age of 55 are the most common causes. Poorly controlled hypertension refractory to medical therapy, worsening of renal function, and flash pulmonary edema may point to underlying RAS. Duplex ultrasonography and magnetic resonance angiography have largely replaced captopril scanning for RAS screening. However, renal angiography still remains the gold standard to diagnose RAS. Treatment options include medical therapy, angioplasty, and surgery. In general, patients with a stenosis greater than 50%, a translesional systolic pressure gradient greater than 15 mm Hg, and difficult-to-control hypertension and/or worsening renal insufficiency are candidates for renal revascularization. Percutaneous transluminal revascularization has evolved to become the preferred revascularization therapy because it is a less invasive and more cost-effective alternative to surgery and is associated with high technical success, as well as a low complication rate. The natural history of RAS is to progress over time, leading to renal artery occlusion, loss of renal mass, worsening of renal function, and, ultimately, end-stage renal disease. It is therefore important to aggressively screen, recognize, and treat the entity early in its course.

Asymmetric septal hypertrophy presenting with cardiogenic shock, complete heart block, and septal infarction despite normal coronaries.

A 37-year-old man, brought in following a syncopal episode, was found to be in cardiogenic shock with a complete infranodal heart block. A temporary transvenous pacemaker and an intra-aortic balloon pump were inserted emergently. Cardiac catheterization revealed a high left ventricular end-diastolic pressure but normal coronary vasculature. An echocardiogram demonstrated a hyperdynamic left ventricle, severe hypokinesis of the septum, and asymmetric septal hypertrophy. An endomyocardial biopsy showed myofibril hypertrophy and disarray. The patient required implantation of a permanent pacemaker for full recovery. Although arrhythmias are common in asymmetric septal hypertrophy, complete atrioventricular block is rare but can cause syncope and cardiogenic shock. This is the first case, reported in the literature, of asymmetric septal hypertrophy in which the patient presented with cardiogenic shock and complete heart block secondary to a septal infarction, despite normal coronaries, and in whom a myocardial biopsy was performed. The case report is followed by a review of the literature on hypertrophic cardiomyopathy associated with complete heart block.

The first clinical experience with a peripheral, self-expanding nitinol stent in the treatment of saphenous vein graft disease: angiographic evidence of late expansion.

The ideal intervention for degenerated saphenous vein grafts (SVG) is still controversial. We report the first use of a peripheral, self-expanding nitinol stent in the treatment of a patient with symptomatic SVG disease. The procedure was well tolerated, without any short- or long-term complications. Quantitative coronary analysis of a 3-month follow-up angiogram revealed a continued expansion of the nitinol stent. Larger scale trials are warranted to evaluate whether the self-expanding nitinol stents can be used alone or in adjunct to other modalities for the treatment of SVG disease. The case report is followed by a literature review of SVG stenting.

Gadolinium-based percutaneous coronary intervention in a patient with renal insufficiency.

We report the first case of using gadolinium as a contrast agent to perform percutaneous coronary intervention in a patient with an acute coronary syndrome and a history of renal insufficiency. The procedure was well tolerated without any complications or nephrotoxicity. The images obtained with gadolinium were of good quality.