Thrombotic Microangiopathy in the Setting of Colorectal Cancer: A Therapeutic Challenge with a Bad Prognosis.

While most cases of thrombotic microangiopathic hemolytic anemias are idiopathic, some can occur in the setting of a malignancy. Differentiating both conditions is crucial to initiate the appropriate treatment. In this case report and literature review, we discuss the occurrence of a thrombotic microangiopathy in a 61-year-old male patient with a treatment-refractory metastatic colorectal cancer invading his bone marrow. Plasmapheresis does not constitute the mainstay of treatment in this setting, as targeting the primary disease is the ultimate management. Treating the condition of our patient has been challenging as multiple lines of treatments of his primary disease had been exhausted. The discrepancy in KRAs status obtained between PCR and later NGS offered a new treatment line with Cetuximab. In this article, we will discuss the different factors that differentiate between idiopathic and cancer-induced microangiopathy. We will emphasize on the fact that the treatment of the primary disease constitutes the most important step in the treatment of cancer-induced thrombotic microangiopathy. We will also raise several explanations to target the disagreement in KRAS status obtained by the different technical modalities.

COVID-19-Associated cardiac pathology at the postmortem evaluation: a collaborative systematic review.

BACKGROUND: Many postmortem studies address the cardiovascular effects of COVID-19 and provide valuable information, but are limited by their small sample size. OBJECTIVES: The aim of this systematic review is to better understand the various aspects of the cardiovascular complications of COVID-19 by pooling data from a large number of autopsy studies. DATA SOURCES: We searched the online databases Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science for concepts of autopsy or histopathology combined with COVID-19, published between database inception and February 2021. We also searched for unpublished manuscripts using the medRxiv services operated by Cold Spring Harbor Laboratory. STUDY ELIGIBILITY CRITERIA: Articles were considered eligible for inclusion if they reported human postmortem cardiovascular findings among individuals with a confirmed SARS coronavirus type 2 (CoV-2) infection. PARTICIPANTS: Confirmed COVID-19 patients with post-mortem cardiovascular findings. INTERVENTIONS: None. METHODS: Studies were individually assessed for risk of selection, detection, and reporting biases. The median prevalence of different autopsy findings with associated interquartile ranges (IQRs). RESULTS: This review cohort contained 50 studies including 548 hearts. The median age of the deceased was 69 years. The most prevalent acute cardiovascular findings were myocardial necrosis (median: 100.0%; IQR, 20%-100%; number of studies = 9; number of patients = 64) and myocardial oedema (median: 55.5%; IQR, 19.5%-92.5%; number of studies = 4; number of patients = 46). The median reported prevalence of extensive, focal active, and multifocal myocarditis were all 0.0%. The most prevalent chronic changes were myocyte hypertrophy (median: 69.0%; IQR, 46.8%-92.1%) and fibrosis (median: 35.0%; IQR, 35.0%-90.5%). SARS-CoV-2 was detected in the myocardium with median prevalence of 60.8% (IQR 40.4-95.6%). CONCLUSIONS: Our systematic review confirmed the high prevalence of acute and chronic cardiac pathologies in COVID-19 and SARS-CoV-2 cardiac tropism, as well as the low prevalence of myocarditis in COVID-19.

A Pin1/PML/P53 axis activated by retinoic acid in NPM-1c acute myeloid leukemia.

Retinoic acid (RA) was proposed to increase survival of chemotherapy- treated patients with nucleophosmin-1 (NPM-1c)-mutated acute myeloid leukemia. We reported that, ex vivo, RA triggers NPM-1c degradation, P53 activation and growth arrest. PML organizes domains that control senescence or proteolysis. Here, we demonstrate that PML is required to initiate RA-driven NPM-1c degradation, P53 activation and cell death. Mechanistically, RA enhances PML basal expression through inhibition of activated Pin1, prior to NPM-1c degradation. Such PML induction drives P53 activation, favoring blast response to chemotherapy or arsenic in vivo. This RA/PML/P53 cascade could mechanistically explain RA-facilitated chemotherapy response in patients with NPM-1c mutated acute myeloid leukemia.

Risk adapted therapeutic strategy in newly diagnosed acute myeloid leukemia: Refining the outcomes of ELN 2017 intermediate-risk patients.

INTRODUCTION: Despite advances in the treatment of acute myeloid leukemia (AML), cytotoxic chemotherapy remains the standard induction regimen. PATIENTS AND METHODS: In this single center retrospective study, we assessed outcomes of 99 consecutive adult AML patients treated with a risk-adapted strategy with a median follow-up of 35.5 months. RESULTS: We identified 24 (24 %), 55 (56 %) and 20 (20 %) patients classified as favorable-, intermediate-, and adverse- risk group respectively, according to the European LeukemiaNet (ELN) 2017 classification. Patients either received idarubicin and cytarabine induction chemotherapy with or without FLT3 inhibitors or hypomethylating agents based on age and comorbidity. The complete response (CR) rate was 76 % (82 % and 61 % in patients aged < 60 and ≥ 60, respectively). For the whole cohort, the 3-year overall survival (OS) was 53 %, being 62 % and 30 % in patients aged < 60 and ≥ 60, respectively. The 3-year leukemia-free survival (LFS) was 54 %, with 56 % and 45 % in patients aged < 60 and ≥ 60, respectively. The 3-year LFS were 58 %, 62 % and 25 % for patients within ELN favorable-, intermediate-, and adverse-risk groups respectively. Twenty-seven (36 %) out of 75 patients with intermediate- and adverse-risk disease underwent allogeneic hematopoietic cell transplantation (allo-HCT) in first CR with 92 % of them receiving post-transplant maintenance consisting of azacitidine in 19 (76 %) patients or sorafenib in 6 (24 %) patients. Of these patients younger than 60 years, the 3-year OS and LFS were 85 % and 69 %, respectively. CONCLUSION: These results indicate an improved OS for AML patients especially in intermediate-risk category who were treated with a total therapy consisting of induction chemotherapy followed by allo-HCT and post-transplant maintenance.

Esophageal Cytomegalovirus and Herpes Simplex virus co-infection in an immunocompromised patient: Case report and review of literature.

Herpes simplex virus and Cytomegalovirus co-infection has been reported to occur in a variety of sites in immunocompromised patients. To our knowledge, few cases of such co-infection have been reported to occur in the esophagus. We report a case of a 60-year-old woman who was maintained on immunosuppressive therapy for a presumed diagnosis of pemphigus vulgaris, who presented with odynophagia. Investigations revealed ulcerative esophagitis caused by both HSV and CMV. The patient was treated with valganciclovir with full recovery. We also present the results of various studies on patients with similar presentation particularly those caused by HSV and CMV co-infection.

Diagnosing Lymphoproliferative Disorders Using Core Needle Biopsy Versus Surgical Excisional Biopsy: Three-Year Experience of a Reference Center in Lebanon.

BACKGROUND: Despite current guidelines, a significant increase in the use of core needle biopsy (CNB) has been noted. Our aims were to determine the profile of patients referred for image-guided biopsies, to assess the diagnostic yield of these biopsies, and to learn whether CNB is an effective alternative to surgical excisional biopsy (SEB). PATIENTS AND METHODS: All lymph node biopsy samples evaluated in the Department of Pathology and Laboratory Medicine from 2014 to 2017 were included. Patients' demographics, biopsy type, and final diagnosis were recorded and classified as diagnostic or nondiagnostic. The reasons for the latter were evaluated and follow-up was obtained, where available. RESULTS: A total of 373 cases, 210 CNB and 163 SEB, were collected. The diagnostic yield was 79% for CNB compared to 97% for SEB. The choice of CNB versus SEB was not dependent on patient's age, gender, or clinical suspicion of malignancy. Failure to reach a diagnosis was due to insufficient or suboptimal tissue in most nondiagnostic CNBs. Lymphoma was equally diagnosed among CNB and SEB. CNB was at an advantage in diagnosing large B-cell lymphomas. CONCLUSION: When performed adequately, CNB is a good substitute for SEB. Strict and specific guidelines need to be updated and adopted to indicate how and when it can be used, including the recommendation of concomitant complementary diagnostic laboratory testing such as flow cytometry. The latter should be readily available in order to not compromise the quality and accuracy of the diagnoses.

Plasma cells and lymphoid aggregates in sleeve gastrectomy specimens: Normal or gastritis?

Lymphoid follicles/aggregates in gastric biopsies have been traditionally linked to Helicobacter pylori gastritis, and less commonly to other inflammatory and neoplastic conditions. The frequency of such aggregates in normal stomachs has yet to be adequately evaluated. This is especially relevant when it comes to diagnosing non-specific chronic gastritis in biopsy specimens with chronic inflammation but no evidence of H pylori infection. Sleeve gastrectomies represent an opportunity to study adequately preserved gastric mucosa in patients who are otherwise asymptomatic and lack a history of gastric disease.To study sleeve gastrectomy specimens to quantify the amount of lymphoid follicles/aggregates and lymphocytic infiltration in normal stomachs.Sixty-eight bariatric sleeve gastrectomies and 13 control specimens from Whipple resections were examined for multiple histologic features including type, quantity, and distribution of chronic inflammation and lymphoid follicles/aggregates. Presence of H pylori was documented by both Hematoxylin and eosin-stained (H&E) and immunohistochemistry (IHC). Clinical information including age, sex, medication intake, prior endoscopy, and/or H pylori infection was recorded. The patient population was divided in 2 groups, H pylori negative versus H pylori positive, and statistical analysis was performed by a biostatistician.Two hundred sixty three fundic sections from 68 bariatric patients were examined. Fifty three patients were found to be H pylori-negative, compared with 15 who were positive for H pylori. Among the H pylori-negative group, the average number of lymphoid aggregates was 3.33, compared with an average of 6.26 in the H pylori positive group (the difference was statistically significant with a P-value of .008). The average number of plasma cells per high power field was 2.15 in the H pylori negative group, compared and average of 5.07 in the H pylori positive group (the difference was also statistically significant with a P-value <.001). Clinically, 10 of the 53 H pylori-negative patients had esophagogastroduodenoscopy (EGD) that showed endoscopic mild non-erosive gastric erythema. The remaining had no documentation of symptoms or medication intake, including Non-steroidal anti-inflammatory drugs (NSAIDs) and Proton Pump Inhibitors (PPI).Our results suggest that the presence of lymphoid aggregates and plasma cells infiltration can be a normal finding in otherwise normal gastric mucosa, though more pronounced in H pylori infected patients.

Molecular profiling of adult acute myeloid and lymphoid leukemia in a major referral center in Lebanon: a 10-year experience report and review of the literature.

Recurrent genetic abnormalities confer distinct morphologic features and play a role in determining the clinical behavior, prognosis and adequate treatment of acute leukemia. In the MENA region, only one study targets the frequency of genetic modifications in AML, reporting a higher occurrence of acute promyelocytic leukemia in Lebanon. Determining the frequency of translocations and gene mutations in acute myeloid and lymphoid leukemia cases in an adult patients' population in Lebanon and comparing the resultant genetic profile with the published international molecular profile of adult acute leukemia. Laboratory results of adult patients diagnosed with AML or ALL presenting to AUBMC for genetic profiling between years 2006 until June 2016 were reviewed. Genetic profiling of AML cases in our CAP accredited molecular diagnostics laboratory consists of a validated lab developed RT-PCR for the detection of RUNX1/RUNX1T1, CBFB/MYH11, KMT2A/MLLT3, PML-RARA, and BCR-ABL and mutations in the FLT3 receptor, NPM1, c-kit and CEPBA genes. The ALL panel tests for the presence of BCR-ABL1, ETV6/RUNX1; KMT2A/AFF1, and TCF3-PBX1. We reviewed 580 AML and 175 ALL cases. In the AML cohort, the M:F ratio was 1.3:1 with a mean age of 50 years. t(15;17) was present in 7.6%, t(8;21) in 4.2%, inv(16) in 3.7%, t(9;22) in 2.2% and t(9;11) in 1.7% of cases. FLT3 mutation (ITD or TKD) was present in 25.2% of all cases and 30.1% of Cytogenetics-normal (CN) patients. Mutations of the NPM1 gene was present in 31.4% of AML cases and in 43.8% of CN patients. Double positive (NPM1+/FLT3+) cases accounted for 20% of NK patients. CEBPA and c-kit mutations were detected in 7.3% and 2.4% respectively. In the ALL cohort, the mean age was 37 years. B- and T-lymphoblastic leukemia constituted 84.6% and 15.4% of ALL cases and the M:F ratio was 1.2:1 and 2.86:1 respectively. B-ALL patients were positive for t(9;22) in 14.2%, t(4;11) in 5.4%, t(1;19) in 2.7% and t(12;21) in 1.4%. T-ALL patients were negative for translocations found in our ALL panel. A lower mean age was found in our adult leukemic Lebanese population as compared to the Western cases. Other interesting findings were the lower percentage of inv(16), lower incidence of TCF3-PBX1, and the mild increase in Philadelphia positivity in our AML cohort. In our ALL cohort, t(9;22) positivity was less than expected for adult lymphoblastic leukemia. Full molecular profiling by next generation sequencing is required for further classification of cases into prognostic categories. This study will be a baseline reference for future research and epidemiological data useful for transplant centers and oncologists both in Lebanon and the region.

Posterior Tibial Nerve Lymphoma Presenting as Tarsal Tunnel Syndrome: A Case Report.

We report a case of isolated posterior tibial B-cell lymphoma of the posterior tibial nerve presenting as tarsal tunnel syndrome. This diagnosis was considered because of the clinical presentation and electrophysiologic abnormalities. It was further confirmed by the magnetic resonance imaging findings of the ankle and tissue pathologic findings. Whole body positron emission tomography confirmed this to be a localized lymphoma involving the peripheral nerve. The patient underwent chemotherapy with complete tumor resolution. She had had no relapse after 8 months of follow-up. Isolated peripheral nerve lymphomas are very rare, and involvement of the posterior tibial nerve has not been previously reported. Furthermore, the present case report highlights the importance of the clinical examination in the diagnosis of tarsal tunnel syndrome before performing surgical decompression.

Review of Hematopathology Consult Cases: A Two-Year Experience in a Tertiary Referral Center in Lebanon.

Hematopathology remains a difficult diagnostic field. With the significant ongoing changes in the classification system that happened over the past several decades, the general pathologist faces many challenges when dealing with patients suspected to have lymphoma or leukemia. The authors assessed referred hematopathology cases that were reviewed by specialized hematopathologists. Of 309 cases, major discrepancy was found in 23% of them. The discrepancy ranged from lymphoma reclassification to other major revisions that had significant impact on patient treatment and management. This paper highlights some of the challenges that may face the general practicing pathologist when dealing with suspected hematopoietic neoplasms.

Undifferentiated Nasopharyngeal Carcinoma Mimicking Hodgkin Lymphoma With CD30 Expression.

The presence of CD30-expressing Hodgkin-like cells with a background of inflammation and eosinophils in a young adolescent is usually diagnostic of classical Hodgkin lymphoma. Herein we present the case of a 12-year-old boy presenting with enlarged cervical lymph node characterized by the presence of Hodgkin-like cells expressing CD30 and EBV-LMP1 with a Hodgkin-like background. The Hodgkin-like cells were negative for CD15, CD20, CD45, and Pax-5. The tumor cells, however, expressed several cytokeratins, confirming the diagnosis of an undifferentiated carcinoma nasopharyngeal type. This case highlights the importance of possessing a high index of suspicion when encountering lymph nodes with Hodgkin-like cells and a Hodgkin-like background, even with CD30 expression, as the differential can include undifferentiated carcinoma nasopharyngeal type.

B-Lymphoblastic Leukemia in Patients With Chronic Lymphocytic Leukemia: A Report of Four Cases.

OBJECTIVES: B-lymphoblastic leukemia (B-LBL) arising in patients with chronic lymphocytic leukemia (CLL) is exceedingly rare and poorly characterized. METHODS: We describe four patients with CLL and concurrent or subsequent B-LBL diagnosed by morphologic, immunophenotypic, cytogenetic, and molecular analysis and reviewed the literature. RESULTS: In three patients, B-LBL followed CLL by 5 to 15 years, and in one patient, B-LBL was diagnosed simultaneously with CLL. In all cases, the CLL had a typical immunophenotype, and the B-LBL blasts showed an immature B-cell immunophenotype with expression of CD10, CD19, and TdT and absence of surface immunoglobulin. In two patients, B-LBL blasts harbored t(9;22)(q34;q11.2)/BCR-ABL1. We sequenced the IGHV genes in both CLL and B-LBL in two patients and showed that IGHV usage differed. CONCLUSIONS: Our data suggest that at least some cases of B-LBL arising in patients with CLL are independent, secondary neoplasms rather than a manifestation of histologic transformation.

Simultaneous occurrence of a CD30 positive/ALK-negative high grade T-cell lymphoma and plasma cell myeloma: Report of a case.

Simultaneous occurrences of T-cell and B-cell neoplasms are rare, and etiological relationships between these two malignancies are poorly understood. We report the case of a 76-year-old man who presented with hypercalcemia, multiple skin nodular lesions, fatigue, episodic fever, and night sweats. PET/CT scan showed diffuse skin and subcutaneous fat plane active lesions, supra- and infra- diaphragmatic active lymph nodes, liver and spleen involvement, bone marrow infiltration, and nonspecific bilateral lung nodules. A skin biopsy showed a high grade CD30-positive/ALK-negative T-cell lymphoma. A bone marrow biopsy showed involvement by the same neoplastic cells. Additionally, a monoclonal lambda restricted plasma cell population (15% of marrow elements) was identified, which, in view of an IgA lambda spike in the serum, was consistent with plasma cell myeloma. To the best of our knowledge, this case is the first reported case of a plasma cell neoplasm associated with an aggressive CD30-positive ALK-negative systemic T-cell lymphoma with skin involvement. Reporting such cases is important as it adds to the pool of rare cases of concomitant T-cell neoplasms and plasma cell myelomas, and might help in determining an etiological relationship, if any, between these two hematological malignancies.

Prediction of celiac disease at endoscopy.

BACKGROUND AND STUDY AIMS: Celiac disease is increasingly recognized worldwide, but guidelines on how to detect the condition and diagnose patients are unclear. In this study the prevalence and predictors of celiac disease were prospectively determined in a cross-sectional sample of Lebanese patients undergoing esophagogastroduodenoscopy (EGD). PATIENTS AND METHODS: Consecutive consenting patients (n = 999) undergoing EGD answered a questionnaire and had blood taken for serologic testing. Endoscopic markers for celiac disease were documented and duodenal biopsies were obtained. The diagnosis of celiac disease was based on abnormal duodenal histology and positive serology. Risk factors were used to classify patients to either high or low risk for celiac disease. Independent predictors of celiac disease were derived via multivariate logistic regression. RESULTS: Villous atrophy (Marsh 3) and celiac disease were present in 1.8 % and 1.5 % of patients, respectively. Most were missed on clinical and endoscopic grounds. The sensitivity of tissue transglutaminase (tTG) testing for the diagnosis of villous atrophy and celiac disease was 72.2 % and 86.7 %, respectively. The positive predictive value of the deamidated gliadin peptide (DGP) test was 34.2 % and that of a strongly positive tTG was 80 %. While the strongest predictor of celiac disease was a positive tTG (odds ratio [OR] 131.7, 95 % confidence interval [CI] 29.0 - 598.6), endoscopic features of villous atrophy (OR 64.8, 95 %CI 10.7 - 391.3), history of eczema (OR 4.6, 95 %CI 0.8 - 28.8), anemia (OR 6.7, 95 %CI 1.2 - 38.4), and being Shiite (OR 5.4, 95 %CI 1.1 - 26.6) significantly predicted celiac disease. A strategy of biopsying the duodenum based on independent predictors had a sensitivity of 93 % - 100 % for the diagnosis of celiac disease, with an acceptable (22 % - 26 %) rate of performing unnecessary biopsies. A strategy that excluded pre-EGD serology produced a sensitivity of 93 % - 94 % and an unnecessary biopsy rate of 52 %. CONCLUSION: An approach based solely on standard clinical suspicion and endoscopic findings is associated with a significant miss rate for celiac disease. A strategy to biopsy based on the derived celiac disease prediction models using easily obtained information prior to or during endoscopy, maximized the diagnosis while minimizing unnecessary biopsies.

Inconclusive or erroneous fine-needle aspirates of breast with adequate and representative material: a cytologic/histologic study.

Adequately cellular and representative fine-needle aspirates (FNAs) of breast have a high diagnostic accuracy. There is, however, a recognized category designated as "gray zone" where a definitive diagnosis cannot be reached. We reviewed our experience in this category to identify useful diagnostic parameters. Twenty-four such FNAs with surgical follow-up were retrieved from AUBMC files (2003-2009). Cytology slides were reviewed blindly. All cases were females, 29-73 years. There were three erroneous and 21 inconclusive diagnoses. The majority (15) was invasive adenocarcinomas: two cribriform, four tubular, one lobular, and eight not otherwise specified. The remaining cases were papillary and fibroepithelial tumors (three each), ductal carcinoma in situ, cribriform (two), and one adenomyoepithelioma (AME). Useful diagnostic features included: (1) Biphasic cell population with focal nuclear atypia and intranuclear and cytoplasmic vacuolar inclusions (AME). (2) Complex clusters of epithelial cells with cribriform architecture (cribriform carcinoma). (3) Rigid tubular epithelial structures with abrupt change in diameter, ending in pointed tips with abnormal branching (tubular carcinoma). (4) Cellular stromal fragments (fibroepithelial tumors). (5) Papillary fibrovascular cores, columnar cells, and three-dimensional papillary epithelial fragments (papillary tumors). Myoepithelial cells classically described in benign aspirates were not always a discriminatory factor. The "gray zone" in breast FNA is usually due to overlapping cytologic features of some benign and malignant lesions. Useful distinguishing cytologic features are described.

Breast implant-associated anaplastic large-cell lymphoma: long-term follow-up of 60 patients.

PURPOSE: Breast implant-associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. PATIENTS AND METHODS: We reviewed the literature for all published cases of breast implant-associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. RESULTS: The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). CONCLUSION: Most patients with breast implant-associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants.

CD105 (endoglin) is highly overexpressed in a subset of cases of acute myeloid leukemias.

OBJECTIVES: To assess CD105 (endoglin) expression in 119 acute myeloid leukemia (AML) and 13 control cases using immunohistochemistry. METHODS: CD105 expression was assessed retrospectively by using immunohistochemistry in bone marrow specimens. RESULTS: CD105 was strongly and diffusely positive in all 9 (100%) AMLs with t(15;17)(q24.1;q21.2), 2 (100%) AMLs with t(8;21)(q22;q22), 1 (100%) AML with t(6;9)(p23;q34), 7 (28%) of 25 AMLs with myelodysplasia-related changes, 1 (33%) of 3 therapy-related AMLs, 3 (16%) of 19 AMLs unclassifiable, 1 (14%) of 7 AMLs with inv(16)(p13.1q22), and 5 (11%) of 45 AMLs not otherwise specified. Uninvolved bone marrow in these cases showed no CD105 expression by erythroid precursors, megakaryocytes, or endothelial or stromal cells. Two of 13 control bone marrow specimens showed partial CD105 positivity in myeloid cells. In 21 strongly CD105+ AML cases tested for the IDH2 mutation, 9 (42%) were mutated (P = .004). CONCLUSIONS: These data suggest that CD105 could be a therapeutic target in a subset of patients with AML.

Cytarabine, Ki-67, and SOX11 in patients with mantle cell lymphoma receiving rituximab-containing autologous stem cell transplantation during first remission.

BACKGROUND: In the current study, the authors report the results of 39 patients with mantle cell lymphoma (MCL) who were treated with chemotherapy and high-dose rituximab-containing autologous stem cell transplantation (ASCT) during their first disease remission. METHODS: The median age of the patients was 54 years. At the time of diagnosis, 87% of patients had Ann Arbor stage IV disease, and 77% had bone marrow involvement. A Ki-67 level of > 30% was found in 11 of 27 patients (40%), and SOX11 (SRY [sex determining region Y)-box 11] expression was found to be positive in 17 of 18 patients (94%). Twenty-seven patients (69%) underwent induction therapy with high-dose cytarabine-containing chemotherapy. Rituximab was administered during stem cell collection at a dose of 1000 mg/m2 on days +1 and +8 after ASCT. RESULTS: The estimated 4-year overall survival and progression-free survival rates were 82% and 59%, respectively. Twelve patients experienced disease recurrence. Fifteen of 16 patients who were alive and in complete remission at 36 months remained so at a median follow-up of 69 months (range, 38 months-145 months). The only determinant of recurrence risk found was a Ki-67 level of > 30%. Seven of 11 patients with a Ki-67 level > 30% experienced disease recurrence within the first 3 years versus only 3 of 16 patients with a Ki-67 level ≤ 30% (P = .02). Patients who received high-dose cytarabine did not have a significantly different risk of developing disease recurrence compared with other patients (P = .7). CONCLUSIONS: Administering ASCT with rituximab during stem cell collection and immediately after transplantation may induce a continuous long-term disease remission in patients with MCL with a Ki-67 level of ≤ 30%.