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SPONTANEOUS CLINICAL REGRESSION IN CHRONIC LYMPHOCYTIC LEUKEMIA: CLINICAL AND BIOLOGIC FEATURES OF 9 CASES FROM THE ERIC REGISTRY
Author(s):
Ilaria Del Giudice
,
Ilaria Del Giudice
Affiliations:
Department of Cellular Biotechnologies and Hematology,Hematology, Sapienza University,Rome,Italy
Andrea Visentin
,
Andrea Visentin
Affiliations:
Department of Medicine,Hematology and Clinical Immunology Unit, University of Padua,Padua,Italy
Livio Trentin
,
Livio Trentin
Affiliations:
Department of Medicine,Hematology and Clinical Immunology Unit, University of Padua,Padua,Italy
Max Flogegard
,
Max Flogegard
Affiliations:
Hematology, Medicine Clinic,Falun Hospital,Falun,Sweden
Chiara Cavallloni
,
Chiara Cavallloni
Affiliations:
IRCCS, Policlinico San Matteo,Pavia,Italy
Ester Maria Orlandi
,
Ester Maria Orlandi
Affiliations:
IRCCS, Policlinico San Matteo,Pavia,Italy
Mattias Mattsson
,
Mattias Mattsson
Affiliations:
Department of Hematology,Uppsala University Hospital,Uppsala,Sweden
Sara Raponi
,
Sara Raponi
Affiliations:
Department of Cellular Biotechnologies and Hematology,Hematology, Sapienza University,Rome,Italy
Caterina Ilari
,
Caterina Ilari
Affiliations:
Department of Cellular Biotechnologies and Hematology,Hematology, Sapienza University,Rome,Italy
Luciana Cafforio
,
Luciana Cafforio
Affiliations:
Department of Cellular Biotechnologies and Hematology,Hematology, Sapienza University,Rome,Italy
Maria Stefania De Propris
,
Maria Stefania De Propris
Affiliations:
Department of Cellular Biotechnologies and Hematology,Hematology, Sapienza University,Rome,Italy
Irene Della Starza
,
Irene Della Starza
Affiliations:
Department of Cellular Biotechnologies and Hematology,Hematology, Sapienza University,Rome,Italy
Nadia Peragine
,
Nadia Peragine
Affiliations:
Department of Cellular Biotechnologies and Hematology,Hematology, Sapienza University,Rome,Italy
Paola Mariglia
,
Paola Mariglia
Affiliations:
Department of Cellular Biotechnologies and Hematology,Hematology, Sapienza University,Rome,Italy
Gianpietro Semenzato
,
Gianpietro Semenzato
Affiliations:
Department of Medicine,Hematology and Clinical Immunology Unit, University of Padua,Padua,Italy
Anna Guarini
,
Anna Guarini
Affiliations:
Department of Molecular Medicine,Hematology, Sapienza University,Rome,Italy
Emili Montserrat
,
Emili Montserrat
Affiliations:
Department of Hematology,Hospital Clinic, University of Barcelona,Barcelona,Spain
Robin Foà
Robin Foà
Affiliations:
Department of Cellular Biotechnologies and Hematology,Hematology, Sapienza University,Rome,Italy
(Abstract release date: 05/18/17) EHA Library. Del Giudice I. 05/18/17; 182493; PB1779
Prof. Ilaria Del Giudice
Prof. Ilaria Del Giudice
Contributions
PDF Abstract
Abstract

Abstract: PB1779

Type: Publication Only

Background
Spontaneous clinical regression in chronic lymphocytic leukemia (CLL) is rare (1% per year). We previously reported on the clinico-biologic features of 9 Binet stage A CLL patients from our Center in Rome who experienced a persistent spontaneous clinical regression of the disease at a median time of 11 years from diagnosis, maintained after 5 more years of follow-up. The lymphocyte count at CLL regression was 3.16 x 109/L (1.3-4.9), with a persistent small CLL clone (CD19+/CD5+/CD23/light chain restricted: 44%, range 5-60%). Biologic features included negative CD38, mutated IGHV, often with VH3-30 and Vk4-1 usage, and a distinctive gene expression profile.

Aims
To conduct a retrospective collection of clinical data and basic biologic information on CLL spontaneous regressions and to make them accessible for future research.

Methods
A registry of spontaneous CLL regressions (absence of lymphadenopathy, splenomegaly or constitutional symptoms, peripheral blood (PB) lymphocytes <4 x 109/L, in the absence of any previous treatment) was launched within the ERIC consortium.

Results

So far, 9 CLL patients showing a spontaneous regression have been reported and 8 have been formally registered, 7 from Italy and 2 from Sweden. Six were males and 3 females, with a median age of 57 years at diagnosis (range 51-82), stage Binet/Rai A/0 in 6, A/I in 2 and B/II in 1. The median lymphocyte count at diagnosis was 14.1 x 109/L (5.3-51.9). Biologic features included: mutated IGHV in 8/8 with VH3-30 (2), VH3-21, VH3-15, VH3-23, VH4-31, VH4-34, VH4-59; CD38 <30% in 6/6; ZAP70 <20% in 4/6; FISH (7 cases): del13q in 4, negative in 3, +12 in 1 case. No patient had undergone treatment, except for one diagnosed in 2009 who received FCR for disease progression in 2013 (lymphocytes 107 x 109/L), obtained a PR and 18 months later developed a Richter’s syndrome - a diffuse large B-cell lymphoma clonally unrelated to CLL - with the concomitant disappearance of the CLL clone from the PB and bone marrow, that has lasted up to January 2017 (lymphocytes 3.5 x 109/L, CLL 0.035 x 109/L). An additional case diagnosed in 2013 (stage A/I, lymphocytes 37.2 x 109/L) reached the highest lymphocyte count 19 months later (91.2 x 109/L) and subsequently started a spontaneous reduction in lymphocytosis down to 39.6 x 109/L in 2015 and to 8.9 x 109/L in January 2017 in stage A/0, indicative of a partial but ongoing CLL regression. Excluding the latter cases, in the other 7, all in stage A/0, the highest lymphocyte count was 16.0 x 109/L (8.9-76.0), the lowest at the last follow-up was 2.8 x 109/L (1.8-4.4), with 0.66 x 109/L CLL cells (0.085-3.0) in the 4 evaluable cases. The median time from diagnosis to clinical regression was 4 years (range 2-17) and this has been maintained for 2 further years (range 0.5-7). One of these cases (mutated VH3-21, +12) seems the most dramatic: in 2008 at diagnosis, the lymphocytes were 51.9 x 109/L, in 2009 a peak at 76.0 x 109/L was recorded; in 2011, when the CLL regression started, the patient underwent several mild viral upper respiratory infections; the CLL complete regression (1.8 x 109/L) persists up to the last follow-up. In 5/9 cases one event - mild viral infections, a cerebral hemorrhage, a stroke, a pelvis fracture and a Richter’s syndrome - occurred before the spontaneous regression, but no relevant drug intake was recorded.

Conclusion
Clinicians should be aware that spontaneous regression is a possibility, albeit infrequent, in the natural history of CLL. The collection and study of such cases within the ERIC registry may shed light on mechanisms leading to spontaneous regression and critical pathways in immunosurveillance in CLL.

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Remission, Minimal residual disease (MRD), Chronic Lymphocytic Leukemia

Abstract: PB1779

Type: Publication Only

Background
Spontaneous clinical regression in chronic lymphocytic leukemia (CLL) is rare (1% per year). We previously reported on the clinico-biologic features of 9 Binet stage A CLL patients from our Center in Rome who experienced a persistent spontaneous clinical regression of the disease at a median time of 11 years from diagnosis, maintained after 5 more years of follow-up. The lymphocyte count at CLL regression was 3.16 x 109/L (1.3-4.9), with a persistent small CLL clone (CD19+/CD5+/CD23/light chain restricted: 44%, range 5-60%). Biologic features included negative CD38, mutated IGHV, often with VH3-30 and Vk4-1 usage, and a distinctive gene expression profile.

Aims
To conduct a retrospective collection of clinical data and basic biologic information on CLL spontaneous regressions and to make them accessible for future research.

Methods
A registry of spontaneous CLL regressions (absence of lymphadenopathy, splenomegaly or constitutional symptoms, peripheral blood (PB) lymphocytes <4 x 109/L, in the absence of any previous treatment) was launched within the ERIC consortium.

Results

So far, 9 CLL patients showing a spontaneous regression have been reported and 8 have been formally registered, 7 from Italy and 2 from Sweden. Six were males and 3 females, with a median age of 57 years at diagnosis (range 51-82), stage Binet/Rai A/0 in 6, A/I in 2 and B/II in 1. The median lymphocyte count at diagnosis was 14.1 x 109/L (5.3-51.9). Biologic features included: mutated IGHV in 8/8 with VH3-30 (2), VH3-21, VH3-15, VH3-23, VH4-31, VH4-34, VH4-59; CD38 <30% in 6/6; ZAP70 <20% in 4/6; FISH (7 cases): del13q in 4, negative in 3, +12 in 1 case. No patient had undergone treatment, except for one diagnosed in 2009 who received FCR for disease progression in 2013 (lymphocytes 107 x 109/L), obtained a PR and 18 months later developed a Richter’s syndrome - a diffuse large B-cell lymphoma clonally unrelated to CLL - with the concomitant disappearance of the CLL clone from the PB and bone marrow, that has lasted up to January 2017 (lymphocytes 3.5 x 109/L, CLL 0.035 x 109/L). An additional case diagnosed in 2013 (stage A/I, lymphocytes 37.2 x 109/L) reached the highest lymphocyte count 19 months later (91.2 x 109/L) and subsequently started a spontaneous reduction in lymphocytosis down to 39.6 x 109/L in 2015 and to 8.9 x 109/L in January 2017 in stage A/0, indicative of a partial but ongoing CLL regression. Excluding the latter cases, in the other 7, all in stage A/0, the highest lymphocyte count was 16.0 x 109/L (8.9-76.0), the lowest at the last follow-up was 2.8 x 109/L (1.8-4.4), with 0.66 x 109/L CLL cells (0.085-3.0) in the 4 evaluable cases. The median time from diagnosis to clinical regression was 4 years (range 2-17) and this has been maintained for 2 further years (range 0.5-7). One of these cases (mutated VH3-21, +12) seems the most dramatic: in 2008 at diagnosis, the lymphocytes were 51.9 x 109/L, in 2009 a peak at 76.0 x 109/L was recorded; in 2011, when the CLL regression started, the patient underwent several mild viral upper respiratory infections; the CLL complete regression (1.8 x 109/L) persists up to the last follow-up. In 5/9 cases one event - mild viral infections, a cerebral hemorrhage, a stroke, a pelvis fracture and a Richter’s syndrome - occurred before the spontaneous regression, but no relevant drug intake was recorded.

Conclusion
Clinicians should be aware that spontaneous regression is a possibility, albeit infrequent, in the natural history of CLL. The collection and study of such cases within the ERIC registry may shed light on mechanisms leading to spontaneous regression and critical pathways in immunosurveillance in CLL.

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Remission, Minimal residual disease (MRD), Chronic Lymphocytic Leukemia

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