LGCmain
Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 429
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size


 
ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 3  |  Page : 490-493
Clinicopathologic spectrum of Waldenström's macroglobulinemia: A single center experience


1 Section of Hematology, Department of Pathology and Microbiology, The Aga Khan University, Stadium Road, Karachi - 748 00, Pakistan
2 Dow Medical College, Karachi, Pakistan

Click here for correspondence address and email

Date of Web Publication22-Oct-2010
 

   Abstract 

Waldenström's Macroglobulinemia (WM) is a B cell neoplasm characterized by infiltration of the bone marrow by a lymphoplasmacytic infiltrate and an IgM monoclonal gammopathy. We report a 15-year review of patients diagnosed with WM at our center. A total of 18 patients were diagnosed and treated at our center during the study period. Neurological symptoms were seen in almost 95% while B symptoms were present in almost 80% of patients. More than two-thirds of patients were anemic at the time of presentation and more than 90% showed bone marrow infiltration with lymphoplasmacytoid cells. Anemia, B symptoms, splenomegaly and neurological symptoms were the primary reasons in the majority of patients to initiate treatment. Chlorambucil was the primary treatment in more than half the patients followed by CVP. The median overall survival in all patients was 29 months (range 22-81 months). WM is a rare disorder and novel therapeutic modalities need to be identified to improve survival in these patients.

Keywords: Hyperviscosity, IgM, Waldenstrφm′s Macroglobulinemia

How to cite this article:
Sajid R, Siddiqui SH, Shaikh U, Adil S. Clinicopathologic spectrum of Waldenström's macroglobulinemia: A single center experience. Indian J Pathol Microbiol 2010;53:490-3

How to cite this URL:
Sajid R, Siddiqui SH, Shaikh U, Adil S. Clinicopathologic spectrum of Waldenström's macroglobulinemia: A single center experience. Indian J Pathol Microbiol [serial online] 2010 [cited 2021 Aug 1];53:490-3. Available from: https://www.ijpmonline.org/text.asp?2010/53/3/490/68288



   Introduction Top


Waldenström's macroglobulinemia (WM) is a B-cell neoplasm characterized by infiltration of the bone marrow by a lymphoplasmacytic infiltrate and an IgM monoclonal gammopathy. [1] It is a rare disorder with incidence of approximately 3 per million per year in western countries. [2] Epidemiological data for Pakistan is not available as only occasional case reports of this disease are published in this part of the world. [3],[4],[5],[6],[7],[8] The diagnostic criteria vary somewhat from the IgM monoclonal gammopathy of any concentration, bone marrow infiltration by small lymphocytes, plasmacytoid cells and plasma cells in a diffuse, interstitial or nodular pattern, and a surface Ig(+)CD19(+)CD20(+)CD5(-)CD10(-)CD23(-) immunophenotype proposed by Owen et al,[9] to any size IgM monoclonal gammopathy of undetermined significance and >10% intertrabecular lymphoplasmacytic infiltrate in marrow with end organ damage as proposed by Rajkumar et al. in 2006. [10] The lymphoma classification of World Health Organization (WHO) defines WM as a subset of lymphoplasmacytic lymphoma (LPL) with bone marrow involvement and IgM monoclonal gammopathy of any concentration. [11]

Disease symptoms can be both due to infiltration of the disease and due to the effects of elevated serum IgM levels. [12] Patients may be asymptomatic and only symptomatic patients are treated. Symptoms may include mucosal bleeding, visual abnormalities and neurological manifestations of hyperviscosity like headache, syncope, seizures and cerebral hemorrhage. [13]

Waldenström's Macroglobulinemia is an incurable disorder and the treatment options include chlorambucil, combination chemotherapy and stem cell transplant. After thorough literature search, no such study from Pakistan or South Asia has been published to the best of our knowledge and only a few case reports have been published from this part of the World. We did a retrospective analysis of this disease at our center for the last 15 years with analysis of clinicopathologic spectrum, treatment given and outcomes in this cohort of patients.


   Materials and Methods Top


This was a retrospective analysis over a period of 15 years from January 1994 to February 2009 at our center, which is a well-equipped tertiary care hospital of our country with facilities for bone marrow transplantation.

A computerized database search (through International Classification of Disease (ICD) version 9.0) for obtaining anonymous information was conducted under the guidelines set by institutional ethical review committee. Patients with established diagnosis of WM were included in the study. The WHO criteria were followed for diagnosis and patients fulfilling those criteria were included in the study. The demographic and relevant data was retrieved using an in-house questionnaire maintaining full confidentiality for the patients The data included clinicopathologic features, laboratory parameters, treatment protocols and outcomes.

Overall Survival (OS) was considered from the time of diagnosis to death. To assess the patient's response to treatment, the criteria developed by 'The International working group on WM Patients' were followed. [1] The response to therapy was evaluated at 6 and 12 months. Complete response (CR) was defined as disappearance of monoclonal protein by immunofixation, resolution of any organomegaly or lymphadenopathy and resolution of any signs or symptoms attributable to WM. Partial response (PR) was defined as 50% or more reduction in serum monoclonal IgM concentration, 50% or more decrease in marrow lymphocytosis, at least 50% decrease in lymphadenopathy or organomegaly, if present and no new symptoms or signs of the disease. Patient was considered to have a Minor response (MR) when there was less than 50%, but at least 25% reduction in serum monoclonal IgM concentration. Finally, Progressive disease (PD) was defined as two measurements showing at least a 25% increase in serum monoclonal IgM, increase in size/number or lymph nodes or organomegaly, development of cytopenias and an increase in symptoms attributable to WM. Stable disease (SD) was considered when the patient did not fulfill criteria for MR or PD.


   Results Top


A total of 18 patients were diagnosed and treated at our center during the study period. The clinicopathologic features are summarized in [Table 1]. Neurological symptoms were seen in almost 95% while B symptoms were present in almost 80% of patients. More than two-third of patients were anemic at the time of presentation and 100% of the patients had showed bone marrow infiltration of greater than 40% with lymphoplasmacytoid cells, lymphoid cells or plasma cells (17 out of 17 patients, bone marrow report of 1 patient was not available).
Table 1 :Clinicopathologic features at the ti me of presentati on

Click here to view


Treatment and Outcomes

Anemia, B symptoms, splenomegaly and neurological symptoms were the primary reasons in the majority of patients to initiate treatment. Chlorambucil was the primary treatment in more than half the patients followed by CVP (cyclophosphamide, vincristine and prednisolone) in five, Fludarabine in one and R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin,Vincristine and prednisolone) in one patient, respectively. Complete response was seen in only one patient, two patients had MRs, one had PD despite treatment and two showed stable disease. There was no difference in response rates among various regimens. The median OS in all patients was 29 months (range 22-81 months). Kaplan Meier Survival statistics are shown in [Figure 1]. Plasmapheresis was done in 10 patients with a median of four sessions per patient. Only one patient was alive in remission, whereas one patient had relapsed disease, eight patients had died and eight patients were lost to follow-up at the time of data analysis. Sepsis was the most common cause of death in four patients followed by cardiopulmonary arrest in two, pneumonia in one and mucormycosis in one patient, respectively.
Figure 1 :Kaplan– Meier survival curve for pati ents with WM

Click here to view



   Discussion Top


We report the clinical features and treatment outcomes of eighteen patients diagnosed with WM at our center over 15 years. This low number of patients over this period indicates that Waldenström's is a rare disorder. However, these patients fulfilled the diagnostic criteria given by various studies. [9],[11] The median age of the patients in our study was 65 years with a male predominance of 2 : 1. Similar values have been reported in other published studies from all over the world. [12],[14],[15],[16] Eleven percent of the patients were asymptomatic at presentation which is lower than other studies. [16] This may be due to the fact that our country is a developing third world country and there is usually a delay in seeking medical advice by many patients resulting in late symptomatic presentation. The frequency of various laboratory manifestations was much higher in this group of patients. Thrombocytopenia was reported in 22.2% of the patients in our study as compared to only 2.4% of patients in studies from the West. Lymphocytosis was seen in 55% of patients in our setup as compared to only 9% reported in Western literature. Likewise, anemia was found to be present in 77% of patients in our study, whereas it varies from 17 to 38% in other studies from West and elsewhere. [16],[17] Thrombocytopenia is usually observed in patients with severe marrow involvement by WM cells. [18] Anemia is probably multifactorial. [12] However, the higher frequency of these laboratory manifestations from our study might be due to the fact of delayed presentation of patients in our society, resulting in greater percentage of bone marrow infiltration by tumor cells. Fifty percent of the patients in our study presented with gastrointestinal abnormalities especially with diarrhea. This may be attributable to deposition of IgM monoclonal light chains in the intestines. [15]

Anemia, neurological symptoms and B-symptoms were more common presenting complaints than reported in other studies [Table 2]. [14],[15],[16],[19] Ninety five percent of our patients had neurological symptoms. Results from other published studies report neurological presentations varying from 10 to 32% of patients in different studies including those from the West. [17],[19] This difference is probably due to greater frequency of hyperviscosity-related manifestations in this group of patients. The spectrum of neurological symptoms varied greatly among different patients in our study and included stroke, confusion, dementia, coma as reported in other studies [Table 2]. [20],[21] Most of our patients required treatment due to these two symptoms. B-symptoms were reported in more than three-fourth of the patients in our study which is almost similar to a Canadian study. [17] This is in contrast to only 28% of patients in a Spanish study. [16] The frequency of hepatomegaly, splenomegaly and lymphadenopathy in our study was reported to be 27.8, 27.8 and 6%, respectively. Review of 45 cases from the Canadian study reported higher percentages of the above with hepatomegaly, splenomegaly and lymphadenopathy being 44, 24 and 29%, respectively. [17] However, our results are almost similar to those reported in the Spanish study. [16]
Table 2 :Comparison of clinical and laboratory features with western literature

Click here to view


First-line Chlorambucil and CVP were found to be well tolerated and led to symptom control. The median survival of patients with WM ranges between 4 and 10 years in different studies [Table 2]. [14],[15],[17],[22] As observed in this study, the median survival was much lower, being 29 months (2.4 years) only, with a range of 22-81 months. This again may be attributable to the delay in seeking medical advice by the patients, resulting in presentation with later stages of this B-cell neoplasm. The most common cause of death in our study was found to be due to sepsis. This may be attributable to the fact that infection is a major cause of death in this part of the world because of the increased prevalence of various infections here. [23]

No significant difference was found among the different treatment regimens used. This has been stated in a number of different studies. [14],[16] Being a small number of case series we could not prognosticate our patients and neither a univariate nor a multivariate analysis of factors impacting survival was statistically possible. Only one patient transformed to acute myeloid leukemia and this has been previously reported separately. [3] In summary, we conclude that Waldenström's is a rare disorder and should be treated with Chlorambucil or CVP; however, novel therapeutic modalities need to be identified to improve survival in these patients.

 
   References Top

1.Treon SP, Gertz MA, Dimopoulos M, Anagnostopoulos A, Blade J, Branagan AR, et al. Update on treatment recommendations from the Third International Workshop on Waldenstrom's macroglobulinemia. Blood 2006;107:3442-6.  Back to cited text no. 1      
2.Groves FD, Travis LB, Devesa SS, Ries LA, Fraumeni JF Jr. Waldenstrom's macroglobulinemia: incidence patterns in the United States, 1988-1994. Cancer 1998;82:1078-81.  Back to cited text no. 2      
3.Khalid S, Adil SN, Khurshid M. Waldenstrom's macroglobulinemia terminating in acute myeloid leukemia. J Pak Med Assoc 2006;56:291-2.  Back to cited text no. 3      
4.Ramakrishnan S, Degenhardt R, Vietzke K. Erythrocyte deformability in Waldenstrom's macroglobulinemia. Clin Hemorheol Microcirc 2000;22:17-20.  Back to cited text no. 4      
5.Kumar S, Das S, Goyal JL, Chauhan D, Sangit V. Bilateral orbital tumor formation and isolated facial palsy in Waldenstrom's macroglobulinemia. Int Ophthalmol 2005;26:235-7.  Back to cited text no. 5      
6.Karmarkar T, Saha A, Verma N, Walker R, Sakhuja V, Datta U. Waldenstrom's macroglobulinemia: A case with lymphocytosis. J Assoc Physicians India 1993;41:458-9.  Back to cited text no. 6      
7.Malaviya AN, Mangalik A. Macroglobulinemia: Report of first three cases from India. J J Assoc Physicians India 1971;19:571-7.  Back to cited text no. 7      
8.Khan GQ, Hassan DG, Masood T, Khan AR. Waldenstrom's macroglobulinaemia with intracerebral haemorrhage. J Postgrad Med 2000;46:187-8.  Back to cited text no. 8  [PUBMED]  Medknow Journal  
9.Owen RG. Developing diagnostic criteria in Waldenstrom's macroglobulinemia. Semin Oncol 2003;30:196-200.  Back to cited text no. 9      
10.Rajkumar SV, Dispenzieri A, Kyle RA. Monoclonal gammopathy of undetermined significance, Waldenstrom's macroglobulinemia, AL amyloidosis, and related plasma cell disorders: diagnosis and treatment. Mayo Clin Proc 2006;81:693-703.  Back to cited text no. 10      
11.Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML, et al. Clinicopathological definition of Waldenstrom's macroglobulinemia: Consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. Semin Oncol 2003;30:110-5.  Back to cited text no. 11      
12.Fonseca R, Hayman S. Waldenstrom's macroglobulinaemia. Br J Haematol 2007;138:700-20.  Back to cited text no. 12      
13.Ghobrial IM, Gertz MA, Fonseca R. Waldenstrom's macroglobulinaemia. Lancet Oncol 2003;4:679-85.  Back to cited text no. 13      
14.Dimopoulos MA, Panayiotidis P, Moulopoulos LA, Sfikakis P, Dalakas M. Waldenstrom's macroglobulinemia: Clinical features, complications, and management. J Clin Oncol 2000;18:214-26.  Back to cited text no. 14      
15.Dimopoulos MA, Hamilos G, Zervas K, Symeonidis A, Kouvatseas G, Roussou P, et al. Survival and prognostic factors after initiation of treatment in Waldenstrom's macroglobulinemia. Ann Oncol 2003;14:1299-305.  Back to cited text no. 15      
16.Garcνa-Sanz R, Montoto S, Torrequebrada A, de Coca AG, Petit J, Sureda A, et al. Waldenstrom's macroglobulinaemia: Presenting features and outcome in a series with 217 cases. Br J Haematol 2001;115:575-82.   Back to cited text no. 16      
17.Krajny M, Pruzanski W. Waldenstrom's macroglobulinemia: Review of 45 cases. Can Med Assoc J 1976;114:899-905.  Back to cited text no. 17      
18.Facon T, Brouillard M, Duhamel A, Morel P, Simon M, Jouet JP, et al. Prognostic factors in Waldenstrom's macroglobulinemia: a report of 167 cases. J Clin Oncol 1993;11:1553-8.  Back to cited text no. 18      
19.MacKenzie RM, Wiernick PH, Canellos GP, Dutcher JD. Macroglobulinemia. Vol 3. Neoplastic Diseases of the Blood. New York: Churchill-Livingstone; 1996. p. 601.  Back to cited text no. 19      
20.Mueller J, Hotson JR, Langston JW. Hyperviscosity-induced dementia. Neurology 1983;33:101-3.  Back to cited text no. 20      
21.Pavy MD, Murphy PL, Virella G. Paraprotein-induced hyperviscosity. A reversible cause of stroke. Postgrad Med 1980;68:109-12.  Back to cited text no. 21      
22.Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP. Diagnosis and management of Waldenstrom's macroglobulinemia. J Clin Oncol 2005;23:1564-77.  Back to cited text no. 22      
23.Murray CJ, Lopez AD. Mortality by cause in eight regions of the world: Global burden of disease study. Lancet 1997;349:1269-76.  Back to cited text no. 23      

Top
Correspondence Address:
Raihan Sajid
Section of Hematology, Department of Pathology and Microbiology, The Aga Khan University, Stadium Road, Karachi - 74800
Pakistan
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.68288

Rights and Permissions


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
  Search
 
  
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
    Introduction
    Materials and Me...
    Results
    Discussion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed3434    
    Printed82    
    Emailed1    
    PDF Downloaded87    
    Comments [Add]    

Recommend this journal