Recurrent infections are common in pts with Waldenstrom’s macroglobulinemia (WM) and may be related to IgA and IgG hypogammaglobulinemia. The impact of therapy and therapeutic responses on humoral immunity in WM is therefore of clinical interest. We examined IgA and IgG levels before and after therapy in 92 serially treated and responding WM patients. Their median age was 59 yrs and 70/92 (76.1%) were previously untreated. Median follow-up for all patients was 11 (range 3-134) months. Pre-therapy, 72/92 (78.2%) and 70/92 (76.1%), and post-therapy 82/92 (89.1%) and 80/92 (86.9%) pts demonstrated IgG (<700 mg/dL) and IgA (<70 mg/dL) hypogammaglobulinemia, respectively. Changes in median IgG and IgA levels by therapy were as follows:

N=Pre-IgGPost-IgGT-TestPre-IgAPost-IgAT-Test
Nucleoside analogue 438 399 0.63 32 38 0.35 
Rituximab 17 455 358 0.29 35 29 0.43 
Rituximab/Thalidomide 19 388 374 0.3 28 24 0.32 
Rituximab/Nucleoside 21 571 423 0.006 55 29 0.05 
CHOP 702 568 0.62 48 30 0.82 
CHOP/Rituximab 14 537 383 0.1 61 36 0.21 
Chlorambucil ± steroids 837 659 0.57 129 66 0.52 
Campath-1H 521 444 0.62 28 27 0.61 
HD Dexamethasone 269 173 NA 27 28 NA 
All therapies 92 480 398 0.008 38 28 0.01 
N=Pre-IgGPost-IgGT-TestPre-IgAPost-IgAT-Test
Nucleoside analogue 438 399 0.63 32 38 0.35 
Rituximab 17 455 358 0.29 35 29 0.43 
Rituximab/Thalidomide 19 388 374 0.3 28 24 0.32 
Rituximab/Nucleoside 21 571 423 0.006 55 29 0.05 
CHOP 702 568 0.62 48 30 0.82 
CHOP/Rituximab 14 537 383 0.1 61 36 0.21 
Chlorambucil ± steroids 837 659 0.57 129 66 0.52 
Campath-1H 521 444 0.62 28 27 0.61 
HD Dexamethasone 269 173 NA 27 28 NA 
All therapies 92 480 398 0.008 38 28 0.01 

Changes in median IgG and IgA levels by response category were as follows:

N=Pre-IgGPost-IgGT-TestPre-IgAPost-IgAT-Test
CR 644 472 0.05 75 37 0.08 
PR 70 415 349 0.09 27 28 0.91 
MR 14 474 394 0.01 38 26 0.02 
N=Pre-IgGPost-IgGT-TestPre-IgAPost-IgAT-Test
CR 644 472 0.05 75 37 0.08 
PR 70 415 349 0.09 27 28 0.91 
MR 14 474 394 0.01 38 26 0.02 

These studies demonstrate that IgA and IgG hypogammaglobulinemia persists despite therapeutic responses, including complete remissions in patients with WM. Futhermore, the therapeutic regimen employed may aggravate persistent IgA and IgG hypogammaglobulinemia.

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