The clinical and pathological findings of plasmablastic lymphoma (PBL) have been described in the literature but the etiology is not well established, and treatment options are poorly defined. We ...reviewed patients with PBL in our institution to characterize the clinicopathologic features in our patient population. In this retrospective analysis from a single academic institution, five patients with PBL were identified and analyzed. Human immunodeficiency virus and human herpesvirus 8 (HHV-8) were identified in 40% (two out of five) and 80% (four out of five) of these patients, respectively. Central nervous system (CNS) involvement was identified in four out of five (80%) patients. Interestingly, three out of five patients had a concurrent or preceding second primary malignancy including small lymphocytic lymphoma, endometrial cancer, and nonsmall cell lung cancer. Most of the patients had advanced disease and a poor performance status at diagnosis. Only two of the patients received systemic chemotherapy with an initial partial response. All five patients died; the median overall survival was 1 month. Our experience in patients with PBL indicates that CNS involvement is more common than reported in the literature. Coexistence of a second primary malignancy may be frequent, and prognosis remains dismal with standard lymphoma therapy. Lastly, the role of HHV-8 in the etiopathogenesis needs further trials.
Objective: Patients with light chain-predominant multiple myeloma have been shown to exhibit shorter survival. Retrospective comparison of clinical and laboratory data was undertaken to ascertain the ...likely cause(s) of this observation. Methods: Records of patients with multiple myeloma seen at 1 institution revealed 316 patients with conventional and 71 patients with light chainpredominant multiple myelomas with secretion of intact immunoglobulins. Laboratory and clinical findings in the 2 groups were compared. Results: Patients with light chain-predominant multiple myeloma had a significantly higher death rate, a higher rate of chronic dialysis, a lower estimated glomerular filtration rate and serum albumin, a significantly higher urine protein concentration, and a significantly higher prevalence of hypertension and blood transfusion requirements. Other clinical and laboratory parameters surveyed were not significantly different between the 2 groups. Conclusion: The shorter survival of patients with light chain-predominant multiple myeloma is clearly associated with renal damage caused by excess free immunoglobulin light chains. Renal damage may be ameliorated by early aggressive treatment with chemotherapy, plasmapheresis, and dialysis; a multi-institutional prospective controlled trial would be needed to test this hypothesis. Keywords: multiple myeloma, serum free light chains, cast nephropathy, light chain--predominant multiple myeloma, eGFR, survival
Imatinib (IM) can be safely discontinued in patients with chronic myeloid leukemia (CML) with sustained complete molecular remission. Previous publications from France and Australia have shown that ...overall 40% maintain MMR or MR5 for up to 5 years after IM is stopped. We report single US center experience with tyrosine kinase inhibitor (TKI) discontinuation. Between 06/2010 and 7/2015, 22 patients with CML in chronic (CP, n=19), accelerated (AP, n=2) and lymphoid blast phase (LBP, n=1) discontinued IM (n=17), dasatinib (DAS, n=3) or bosutinib (BOS, n=2), and were monitored by qPCR for BCR-ABL1 monthly for the first 3 months, quarterly for the following 2 years and then bi-annually. TKI was restarted in case of confirmed loss of MMR on a repeat qPCR. Reason for TKI discontinuation was predominantly driven by patients' request and TKI intolerance. Median age was 66 (range, 21-84). The 3 who discontinued DAS had IM-resistant (loss of CCyR; n=1), IM-intolerant CP (n=1), or received DAS as first-line agent (n=1). BOS was discontinued for IM-intolerant CP (n=1), or while in CR2 in a patient with LBP that transformed from IM resistant CP and relapsed following chemotherapy (HCVAD). Median duration of TKI therapy pre-discontinuation for the entire cohort was 89 months (range, 26-106). Three patients are not evaluable due to short follow-up (TKI stopped between 5/2015 and 7/2015).
With a median follow-up of 40 months (range, 8-60), 7 (41%, 6 CP and 1 AP), all previously on IM lost MMR a median of 3 months (range, 3-24) after TKI was stopped and restarted IM. Loss of CHR occurred 13 months after loss of MMR in 1 patient who elected not to restart IM at the time MMR was lost, due to complications from cardiac transplant rejection. All 7 achieved MMR following restart of IM. Median duration of TKI therapy pre-discontinuation for these 7 patients was 60 months (range, 48-98). 12 patients (59%, 10 CP, 1 AP, 1 LBP) remain off TKI and have not lost MMR, 8 with continuously undetectable BCR-ABL1; and 4 had 1-2 transient detectable BCR-ABL1 at MR4 levels. Median duration of TKI therapy pre-discontinuation for these 12 patients was 87 months (range, 26-106). Loss of MMR-free survival is depicted in the Figure. We conclude that, similar to previous reports, TKI can be safely discontinued in patients with CML without reappearance of BCR-ABL1 in 50-60%.
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Jillella:Seattle Genetics, Inc.: Research Funding. Kota:Leukemia Lymphoma Society: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees.
APL is a highly curable malignancy with reported survival above 90% in many large co-operative group studies. The most recent GIMEMA trial in low and intermediate risk patients showed an expected ...survival of 98% in the ATRA/Arsenic trioxide arm and 91% in the ATRA/chemotherapy arm. The early mortality was very low as with other large trials. These spectacular results are not evident in studies from cancer registry data. A recent study from US SEER data showed that the 1 and 5 year relative survival in APL patients is 71% and 65%. Studies from Swedish cancer registry and Brazil also show that the early mortality is approximately 30%. This is in contrast to observation in clinical trials where the early mortality is around 5%. The common causes of death are hemorrhagic complications (HC) 70%, differentiation syndrome (DS) 20% and infection 10%. HC are unique to this condition and are due to DIC seen in majority of patients. Current trials that are using a risk adapted strategy, using new drugs, changing the sequence, withholding maintenance treatment etc may result in a modest improvement in survival. However the intervention most likely to improve survival in the general population in the US is to decrease early deaths. We report our results showing that the use of a set of streamlined treatment guidelines along with support from experts can decrease early deaths in APL.
At Georgia Regents University, between 7/2005 and 6/2009, 19 patients were diagnosed with APL. 7 patients (5 high-risk and 2 low-risk) died during induction resulting in an unusually high and unacceptable mortality rate of 37%. All patients who survived induction are in remission at present. The high early death rate prompted us to develop a simple 1.5 page treatment algorithm that focuses on quick diagnosis, prompt initiation of therapy, and proactive and aggressive management of all the major causes of death during induction. More importantly we made our treatment guidelines available to smaller outlying leukemia treatment centers and helped the treating oncologists manage the patient during induction.
From 11/2010 to 05/2013, we treated 8 patients at GRU and helped manage 14 patients at 8 practices. Age range was 21-70 years. Nine patients were high-risk, eight intermediate and five low-risk. There were no deaths during induction. Only 1 patient (4.5%) had HC and eight had DS.
While we recognize that this is a small cohort, our own experience and recent SEER based studies show that early mortality is a significant problem in the United States. We show that a streamlined treatment algorithm that we developed independently due to our poor outcome along with help from experts will lead to better outcomes in this curable disease. A similar approach pioneered by investigators in Brazil clearly shows this to be an effective model to decrease early deaths in APL. We believe our experience warrants large scale implementation of our strategy in an attempt to decrease early mortality in APL. We were awarded a $1.68 million grant by the Leukemia Lymphoma Society to implement this protocol in the states of Georgia and South Carolina with a population of 15 million over a 3 year period.
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Jillella:Lymphoma Leukemia society: Research Funding. Awan:Lymphoma Research Foundation: Research Funding; Spectrum Pharmaceuticals Inc.: Speakers Bureau. Kota:Teva: Speakers Bureau; Ariad: Advisory board, Advisory board Other.
APL is a highly curable malignancy with cure rates of greater than 90% in most co-operative group trials. Population-based studies show that the survival is only about 65-70% with up to 30% early ...deaths. The most common reasons of early deaths are bleeding, differentiation syndrome (DS) and infection. Differentiation syndrome is very peculiar to this disease and potentially fatal unless recognized early. The wide variety of clinical presentations associated with DS might lead to delay in diagnosis in some patients which may lead to poorer outcomes. European Leukemia Net recommendations suggest that congestive heart failure (CHF) is one of the presenting features of DS and most of the reports on cardiac abnormalities focus on pericardial effusion. Cardiac stunning is only briefly reported in the literature. Cardiac stunning might be a result of cytokine storm attributable to tumor lysis in addition to being part of the DS. Here we report the incidence of CHF in patients undergoing induction for APL.
We performed a retrospective chart review on patients diagnosed with APL who received induction between December 1, 2004 and July 31, 2013 at Georgia Regents University and also patients who were referred to us from surrounding treatment centers with whom we co-manage these patients. Baseline and follow up ejection fractions (EF) were recorded by echocardiogram or nuclear medicine scan. We evaluated patients who had a drop in EF during the induction period.
41 consecutive patients with APL with normal ejection fraction at diagnosis were evaluated. 1 patient refused treatment and was excluded. 38/40 patients received idarubicin and ATRA remission induction and 2 patients received Arsenic and ATRA. There were seven deaths during induction phase of treatment In the surviving patients, 10 patients had a repeat ECHO during the first 30 days of induction phase for suspected cardiomyopathy. 5 patients (15.1% of surviving patients) demonstrated a decrease in EF and all five were in the anthracycline group. The age range of patients with drop in EF was 30-75 years. Absolute drop in EF was between 10- 35%. Only one patient had mild elevation in troponins while others had no elevation. 3 out of the 5 patients had significant DS. Of the surviving patients, 4 out of 5 patients recovered their EF completely with one patient recovering partially to 45-50% (from 20-25%).
Anthracyclines, along with ATRA, are still the mainstay of treatment for this curable malignancy. Although the incidence of cardiac abnormalities is described with repeated courses of anthracyclines, a single dose of anthracyclines can also play a role in cardiac injury. The highly inflammatory state present during the early treatment of APL might also play a role in cardiac injury resulting in higher number of patients with decreased EFs. DS clinical presentation most commonly involves dyspnea and edema, which are also symptoms of heart failure. Prompt cardiac evaluation should be undertaken to rule out congestive heart failure as an early start to therapy will lead to improved outcomes.
Awan:Lymphoma Research Foundation: Research Funding; Spectrum Pharmaceuticals Inc.: Speakers Bureau. Jillella:Lymphoma Leukemia society: Research Funding. Kota:Teva: Speakers Bureau; Ariad: Advisory board, Advisory board Other.
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