T-cell chronic lymphocytic leukemia or small-cell variant of T-cell prolymphocytic leukemia: a historical perspective and search for consensus.

There is a rich history behind the extinct entity 'T-cell chronic lymphocytic leukemia (T-CLL)' and the now-established replacement, small-cell variant of T-cell prolymphocytic leukemia (T-PLL-sv). Herein, we review the history of the events, observations, and discussions that led to this replacement. We also provide a systematic analysis of all previously reported cases of T-PLL-sv as well as our four new additional cases. Despite the higher frequency of a normal karyotype and perhaps an overrepresented CD4(-) CD8(-) immunophenotype among these patients (compared to T-PLL in general) as well as bland morphology (that makes them superficially appear more similar to B-CLL), we argue that the current World Health Organization (WHO)-based classification as T-PLL-sv is adequate and should continue for the time being. Morphologically, T-PLL-sv represents approximately one-fifth of all T-PLL cases. However, morphology alone does not determine the clinical course and should not be the basis for clinical decision making and prognostication. We propose a clonal evolution model in which mature T-cell leukemias classified in the past as T-CLL are perhaps T-PLL diagnosed early in the course of the disease. Future research using next-generation sequencing, comparative genomic hybridization, and molecular array studies, including serial analyses of individual cases over time, is needed to better identify this rarely diagnosed, inherently controversial form of T-cell leukemia.

Spontaneous remission of acute myeloid leukemia.

Spontaneous remission (SR) of acute myeloid leukemia (AML) is rare. We collected all 46 reported cases of AML with SR. Fever occurred in 91.3% of cases before remission, which was largely due to pneumonia (54.5%) and bacteremia (24.2%). Pneumonia and bacteremia were significantly more common among those who achieved complete remission (CR) compared to those who achieved only a partial remission (p = 0.032). Although 88.6% of remissions were CR, the median duration of remission was only 5 months. Eight cases did not relapse during the follow-up period. The mechanism of SR in AML likely involves the stimulatory effect of systemic febrile infection on the immune system. Immediate treatment of infections and fever may contribute to the rarity of SR in AML. The results of this review improve our understanding of the important role of the immune system in countermanding AML and may provide new ideas for immunotherapy.

Delay in the administration of all-trans retinoic acid and its effects on early mortality in acute promyelocytic leukemia: final results of a multicentric study in the United States.

Early death (ED) occurs in 10-30% of patients with acute promyelocytic leukemia (APL). Is all-trans retinoic acid (ATRA) promptly given and does it decrease overall early mortality? ATRA was administered within 24h of morphological suspicion in only 44% of the 120 consecutive patients treated in the four collaborating centers. Absence of disseminated intravascular coagulation (p=0.012) and admission to a non-university-affiliated hospital (p=0.032) were independent predictors of ATRA delay. ED occurred in 17% of patients, and was independently correlated only with ICU admission (p=0.002). Our results do not demonstrate that prompt (versus delayed) ATRA administration decreases overall early death.

Acute myeloid leukemia following solid organ transplantation: entity or novelty?

Due to the rarity of the disease, the characteristics of acute myeloid leukemia following solid organ transplantation (post-transplant AML; PT-AML) are unclear; furthermore, it is not known for certain whether PT-AML is a separate entity or not. We provide a systematic review of all previously reported cases of PT-AML in the English literature (n = 51). 45% of cases occurred after renal transplantation, and 72% were males. The median age at diagnosis of AML was 50 yr, with a median transplant-to-AML interval of 3.8 yr and a rapid decline in incidence after 5 yr. 26% of patients were asymptomatic at the time of presentation, and 42% were pancytopenic. M0/M1/M2, M3, M4/M5, and M6/M7 subtypes comprised 17%, 25%, 39%, and 19% of all cases, respectively. 36% of patients had unfavorable cytogenetic risk disease. The median overall survival was only 3 months. We observed several transplant-specific features: (i) The transplant-to-AML interval follows two very different patterns between renal vs. liver transplant patients. (ii) All 4 cases of donor cell leukemia occurred after liver transplant. (iii) Unfavorable risk disease was marginally significantly more common among renal compared with liver transplant patients (P = 0.057). Our results suggest that PT-AML is a separate entity with distinct characteristics, which need to be investigated further in future research. Heavy post-transplant immunosuppression likely plays a key role in the pathogenesis of PT-AML.

Therapy-related acute promyelocytic leukemia: a systematic review.

The incidence of therapy-related acute promyelocytic leukemia (t-APL) is apparently rising. We systematically reviewed the English literature until March 15, 2013, and collected a total of 326 t-APL cases, with the following results: (1) t-APL affects predominantly middle-aged adults with a median age at diagnosis of 47 years and a female-to-male ratio of 1.7:1; (2) after an incidence peak at 2 years following the completion of treatment for the primary antecedent disease, the risk of developing t-APL quickly diminishes with time; (3) the four most common primary antecedent conditions are breast cancer, hematological malignancies, multiple sclerosis, and genitourinary malignancies; (4) topoisomerase II inhibitors and radiation represent the most common potential risk factors; (5) despite different DNA damage "hot spot" sites, t-APL has no significant clinicopathologic differences from de novo APL (dn-APL); (6) t(15;17) is the sole cytogenetic abnormality in the vast majority of patients; (7) only a small minority of cases have a myelodysplastic or pancytopenic preleukemic phase; (8) more than one-third of patients come to medical attention incidentally (i.e., due to laboratory abnormalities), while the most common symptom is mucocutaneous bleeding, and 79 % have clinical DIC; and (9) the remission rate of t-APL is about 80 %, similar to dn-APL.

Primary adrenal lymphoma: a systematic review.

Fewer than 200 cases of primary adrenal lymphoma (PAL) have been reported. We have systematically reviewed all 187 cases of PAL reported in the English literature until June 2013, from which we drew the following conclusions: PAL is typically a highly symptomatic and aggressive, metabolically hyperactive, hypovascular, hypoechoic (and heterogeneous on ultrasound), hypodense (with slight to moderate enhancement on computed tomography), high-grade lymphoma, primarily affecting elderly males and presenting with large bilateral adrenal masses. Most cases have adrenal insufficiency, B-symptoms, and elevated lactate dehydrogenase. Hepatosplenomegaly, lymphadenopathy, concurrent or prior immune dysregulation, and bone marrow involvement are uncommon. Epstein-Barr virus positivity is observed in more than half of cases and the disease is disseminated at presentation in 18 % of cases. The two most common WHO 2008-defined PAL subtypes are diffuse large B cell lymphoma (78 %) and peripheral T cell lymphoma (7 %). The prognosis of PAL has improved with the advent of rituximab-containing chemotherapeutic regimens. According to our results, administration of chemotherapy and adrenal insufficiency are significant independent predictors of prognosis.