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B-cell lymphoma

Short summary

59-year-old-male underwent biopsy, after founding epigastric mass, and was diagnosed with B-cell lymphoma. He was treated as an aggressive lymphoma with R-CHOP. Because of neurtopenia, the planned 6 cycle regimen was not completed and a radiation course was administered. Since then the patient feels well, but continues to have prolonged and persistent neutropenia with mild thrombocytopenia. The expert suggests differential diagnosis of the bone marrow problem, and recommends additional diagnostic workup.

Patient's questions
The patient would like to have the expert's opinion regarding:
1)    Diagnosis
2)    Therapeutic strategy
3)    Prognosis
4)    Recommended hematologists.
Medical Background
This is 59 year old gentleman with the following medical history:
  • Lumbar surgery (disk)
  • Hyperlipidemia
  • Diabetes mellitus
  • Atherosclerotic cardiovascular disease, acute myocardial infarction and PTCA with stent
  • Hepatitis (C ? Status ?)
In Sept 2006, an epigastric (gastric ? lymph nodes ?) mass was found, with symptoms (weight loss). A biopsy (how ? what type of biopsy ?) diagnosed B-cell lymphoma (what is the histopathological report ? Which are the cells: large ? small ? what is the lymph node structure ? follicular or diffuse ?) What are the immunohistochemical stainings ? We do not know anything about the staging process (other nodes in the body ? CT ? PET-FDG ? ), nor we know about the bone marrow prior to the treatment (very important !). We do not have information on the possibility of extra-nodal involvement. We are told that the IPI was high (3).
The patient was treated as an aggressive lymphoma with R-CHOP. Unfortunately, following the 4th chemotherapeutic cycle, because of neurtopenia, the planned 6 cycle regimen was not completed and a radiation course (3000r) was administered.
Since then (early 2007), I understand that the patient feels well (asymptomatic ?), there is a residual mass per CT (where ? size?) but no uptake in PET-FDG. However, the patient continues to have prolonged and persistent neutropenia (600 ANC), with mild thrombocytopenia (70-90k), no real anemia and high MCV. Bone marrow analysis (twice) was interpreted as not consistent (??) with myelodysplasia (but missing information does not allow to draw conclusions: cellularity ? fibrosis ? morphology of the three hematopoietic lineages ? cytogenetics ?)  
Medical opinion
Evaluation and Comments:
As mentioned above missing information makes it very difficult to draw definite conclusions and make relevant suggestions. I would be happy to re-discuss the case having all this lacking information.
However, assuming that we do not have more relevant details, I will have to assume that the diagnosis was aggressive, apparently Diffuse Large B-cell Lymphoma. This was treated (appropriately) with R-CHOP.
The differential diagnosis of the bone marrow problem, with the severe neutropenia and the other mild abnormalities, includes:
  • Bone marrow damage to the chemotherapy, especially the combination with the antibody therapy (Rituxan), and also the RT. Indeed, Rituxan is capable of causing serious and prolonged neutropenia, even months, and up to a year ! In most case, if indeed that is the case, it is usually reversible with spontaneous recovery, although in some case it is permanent.
  • Myelodysplastic syndrome (MDS) cannot be excluded based on the currently available information. It could be that the disease existed prior to or developed following the lymphoma. This can be confirmed by a full bone marrow analysis with a biopsy, cytogenetics and so on.
  • The role of the liver disease is unclear to me at the present time. Progressive liver disease, especially, if liver cirrhosis has already developed (there are clues for that from the imaging testing). Such a hepatic problem can also be responsible for the thrombocytopenia and neutropenia via hypersplenism, although in such a case one would expect also anemia. Nevertheless, a hepatological consult with probably liver biopsy, might help.
  • Other reasons, such as chronic viral infection (EBV ? CMV ? hepatitis ? HIV ?), collagen vascular / auto-immune disease, other drug-induced bone marrow damage, alcohol, B12 or folic acid deficiency – are all possibilities that are less likely but not impossible.
Recommendations & Answers to questions:
  • I would try to complete the diagnostic workup in an attempt to establish a definite diagnosis and to find the reason for the persistent neutropenia (see above for details).
  • In general, the therapeutic strategy in the case of the lymphoma appears to be reasonable, again, taking into consideration, the missing information.
  •  Evaluation of the prognosis, as well as taking additional therapeutic steps now, appear to impractical before we proceed with a more accurate diagnosis
  • There are several excellent Italian hematologists, whom I all know personally and can recommend, if the patient or the family would like to proceed with a personal consult.
    • Prof. Titziano Barbui (Bergamo)
    • Prof. Antonio Palumbo (Turino)
    • Prof. Valeria Santini (Firentze)
    • Prof. Mario Cazzola and Dr. Luca Malcovati (Pavia)