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CLL Complications

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Date: August 10, 2003

by Chaya Venkat

Removal of Original Factory Equipment

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My knee-jerk response is decidedly negative, when contemplating removal of any factory installed original equipment. But I am gradually coming around to the point of view that for some CLL patients it might be better to jettison a badly infiltrated spleen than live with the consequences of keeping it. 

CLL is associated with the immune-mediated disorders autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). The first makes you anemic, and the second reduces the platelets in your blood to the point where it does not clot properly, and any small cut or bruise can become a serious problem. Initial treatment with corticosteroids such as prednisone is often helpful in controlling these problems, but some patients do not show sustained benefit. Part of the therapy decision quandary is that anemia and thrombocytopenia become problems most often as the CLL progresses, and therapy is required to control the CLL. This is exactly when having a huge swollen spleen may be an issue, since it may compete with the rest of your body for the precious drugs you need to fight the CLL. It is intuitively easy to see that the efficacy of therapy is reduced, if a substantial portion of the drugs are going down the splenic drain, so to speak. Splenectomy is a well understood operation, and it is an option to be considered in CLL, under these conditions. One of the problems is that patients with low red blood cells and low platelets are not always the best candidates for major surgery. Do you take care of the spleen first, to fix the anemia and thrombocytopenia problems, or do you have to wait till you get a window of opportunity in the red blood cell and platelet numbers to get the job done? Details, details. But very important ones.

Once the spleen has been identified as the major source of the problem, and you have decided to bid it a fond farewell, there are other decisions to be made: if the spleen is not too huge, laparoscopic removal may be possible. This involves a small incision and carries a much smaller price tag in terms of recovery time, pain and suffering etc. In some cases, where the swollen spleen is too large, such an elegant approach may not be possible, and a full blown incision is needed to get it out. 

Recently, partial splenectomies have been proposed, preserving a part of the spleen called the splenic pedicle, supplied by blood flow from only by the splenogastric vessels. It is thought to have fewer postoperative complications. But after an early postoperative improvement, things may slide again for some patients. My worry with this type of an approach would be that there is a lot less statistical data available on this approach, as opposed to getting rid of the whole spleen. But it is certainly an option to consider, there may be benefits that outweigh the risks. The spleen **is** an important organ. While it is possible to live without it, it certainly makes one more vulnerable to infections that can very quickly get out of control if not handled correctly. If you live in the hinterlands, far from good medical help, and you are the type that likes to give a fever a good few days before you decide to do anything about it, full splenectomy can be a big problem for you. Preserving even a small portion of the spleen and its function may have an advantage in that case. The last abstract below discusses partial splenectomy. 

Another option to splenectomy is radiation. Typically, only a partial response is obtained, with reduction in spleen size accompanied and relief of symptoms (pain, abdominal discomfort, and sweating), as well as improvement in ITP or hemolytic anemia. The usual remission period is about a year or so. The idea is that the time may be used to stabilize the patient sufficiently to make for a better surgery candidate, the radiation therapy is usually followed by surgical removal of the spleen. (See the third abstract below). 

M. D. Anderson has done a review of 77 patients who had splenectomy. (See first abstract below). The comparison was made against a group of patients who kept their spleens, but were treated instead with Fludarabine to get at the underlying CLL, and thereby hopefully address the AIHA and ITP issues. Again, based on just the details in the abstract, it appears splenectomy was successful and in fact might have done better than chemotherapy for this select group of patients. The authors felt that splenectomy should be considered sooner rather than later during the course of the progression of the disease. Makes sense, if you are going to get rid of it anyway, why wait around and let it gum things up for the rest of your body. Sort of like a divorce. Once you know it is inevitable, might as well get it over with. One last comment: if I were in the market for a splenectomy, this is surely one review article I would read in detail, get my mind around each and every last statistical nuance. 

The number and seriousness of post-operative complications are discussed in the second abstract below. Based on 135 patients who underwent splenectomies, post-operative complications were observed in 52%, and "only" 9% of the patients died as a result of the surgery. The complications after surgery were greater for patients with huge spleens, that is to be expected. But I cringed when I read that CLL patients had more complications than patients with Hodgkin's Disease, or Hairy Cell Leukemia. Just once, for a change, I would like our guys to get a brake, be the ones with the better response. Oh well. CLL sucks, what else is new.  


J Am Coll Surg. 1997 Sep;185(3):237-43.

Role of splenectomy in chronic lymphocytic leukemia.

Cusack JC Jr, Seymour JF, Lerner S, Keating MJ, Pollock RE. 

Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX. 

BACKGROUND: The benefit of splenectomy, performed for complications of chronic lymphocytic leukemia (CLL) including autoimmune hemolytic anemia, thrombocytopenia, hypersplenism, and symptomatic splenomegaly, has not been clearly demonstrated. The objective of this study was to determine if splenectomy achieves a predictable hematologic and survival advantage over conventional chemotherapy in patients with CLL. STUDY DESIGN: A retrospective review was performed of 77 consecutive patients with CLL who underwent splenectomy between 1970 and 1994 at the University of Texas M. D. Anderson Cancer Center. Indications for splenectomy, pre- and postoperative hematologic profiles, response to splenectomy, and time to progression and death were recorded. Kaplan-Meier life tables were constructed, and a comparison to an age- and gender-matched cohort of CLL patients treated with fludarabine and no splenectomy was performed using log rank statistical analysis. RESULTS: Seventy-six percent of the patients studied were Rai stage III/IV. Twenty of 29 patients with hemoglobin counts (Hb) < or = 10 g/dL and 11 of 18 patients with platelet counts (plt) < 50 x 10(9)/L achieved an excellent hematologic response to splenectomy. Splenectomy significantly improved survival in patients with Hb < or = 10 g/dL or plt < or = 50 x 10(9)/L (p = 0.025). Thrombocytopenia did not significantly increase postoperative morbidity, and mortality rate was not significantly different between treatment groups. CONCLUSIONS: Splenectomy significantly improves survival in selected subgroups of patients with advanced-stage CLL over that achieved with conventional chemotherapy. Based on these results, splenectomy should be performed early in the course of the disease in CLL patients with either an Hb < or = 10 g/dL or plt < or = 50 x 10(9)/L.

PMID: 9291400

Ann Surg. 1996 Mar;223(3):290-6.

Postoperative complications after splenectomy for hematologic malignancies.

Horowitz J, Smith JL, Weber TK, Rodriguez-Bigas MA, Petrelli NJ.

Roswell Park Cancer Institute, Division of Surgical Oncology, Buffalo, NY.

OBJECTIVE: The authors analyzed the frequency and character of postoperative complications after splenectomy in patients with hematologic malignancies, and correlated these findings with preoperative conditions that could have predicted their outcome. 
SUMMARY BACKGROUND DATA: Splenectomy is performed for hematologic malignancies for diagnostic and therapeutic indications. The role of splenectomy for lymphoproliferative and myeloproliferative malignancies is complex and sometimes controversial. 
METHODS: The medical records of 135 patients undergoing splenectomies for hematologic malignancies at Roswell Park Cancer Institute from January 1, 1984 to December 31, 1993 were reviewed retrospectively. These included Hodgkin's disease (HD), hairy cell leukemia (HCL), non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), and a miscellaneous group. 
RESULTS: The overall postoperative complication and mortality rates for all patients were 52% and 9%, respectively. The complication rate was 63% for patients whose spleens weighed greater than 2000 g, and 29% for patients whose spleens weighed less than 2000 g (p = 0.001). Seventy-three percent of the postoperative deaths were due to septic complications, only one of which was caused by an encapsulated organism. Complications occurred in less than 20% of patients with the diagnosis of HD and HCL; more than 50% of patients with NHL, CLL, and CML suffered postoperative complications. CONCLUSIONS: Splenectomy performed in patients with hematologic malignancies is a potentially morbid procedure. Splenic size was the only preoperative factor found to be predictive of postoperative complications. The complication rate differed significantly between the different diagnostic subgroups. 

PMID: 8604910

Am J Hematol. 1985 Jun;19(2):177-80.

Spleen irradiation in chronic lymphocytic leukemia (CLL): palliation in patients unfit for splenectomy. 

Aabo K, Walbom-Jorgensen S.

In 22 patients with CLL given 30 courses of spleen irradiation, 23 responses were observed (77%, 95% confidence limits, 58-90%). Response was defined as reduction in palpable spleen size accompanied by relief of symptoms (pain, abdominal discomfort, and sweating) or improvement in hypersequestration or hemolytic anemia. Reduction in leukocyte count alone was not regarded as response. All responses were partial. The median response duration was 1 year. Subsequently, three patients underwent splenectomy. The median survival from the beginning of spleen irradiation was 2.5 years (range: 1 month-greater than 5 years). Only six patients had minor side effects from the gastrointestinal tract. The hematologic effect was most pronounced on the white blood cell count, but also the platelet count was affected. It is concluded that spleen irradiation is a gentle and effective alternative in CLL patients suffering from splenomegaly (pain and hypersplenism), refractory to chemotherapy and glucocorticosteroids and unfit for splenectomy. Splenic irradiation may also be used with benefit preoperatively before splenectomy in patients with excessive splenomegaly and hypersplenism. 

PMID: 2408466

Ann Hematol. 2003 Aug 2.

Subtotal splenectomy for the treatment of chronic lymphocytic leukemia.

Petroianu A.

Department of Surgery, Medical School of the Federal University of Minas Gerais, Avenida Alfredo Balena 190, MG 30130-100, Belo Horizonte, Brazil.

Although splenectomy is helpful in the management of selected patients with chronic lymphocytic leukemia (CLL), in most cases this procedure is accompanied by a greater morbidity and mortality, mainly due to sepsis. Thus, it may be proposed that a conservative procedure that reduces the spleen size may have an effect similar to that of total spleen ablation for the treatment of CLL. The present paper describes our experience with an 81-year-old patient submitted to subtotal splenectomy for treatment of CLL. Indications for surgery were uncontrolled leukemic activity and intense abdominal discomfort due to the huge spleen. The good results obtained with subtotal splenectomy in the present case indicate that this procedure may be a new alternative for the treatment of CLL when removal of the spleen is indicated.  

PMID: 12904901

Laparoscopic Splenectomies for Massive Spleens

Following up on a member's lead, with a little digging I came across a more recent article, 2003 vintage. Sounds like there may be some additional morbidity risks associated with the laparoscopic removal of very large spleens. That does not mean you should not discuss this option with your doctors, your case may be the one that is just right for this approach. In any case, this abstract seems to talk about really large spleens, may not be relevant for most of us. Don't let the statistics spook you, OK? But I hope it does get those of you procrastinating the decision to come to grips with it. 

Quote: In splenectomy surgery, "Multivariate analysis found splenic weight to be the most powerful predictor of morbidity".


Ann Surg. 2003 Aug;238(2):235-40.

Massive splenomegaly is associated with significant morbidity after laparoscopic splenectomy. 

Patel AG, Parker JE, Wallwork B, Kau KB, Donaldson N, Rhodes MR, O'Rourke N, Nathanson L, Fielding G. 

Departments of Surgery, Haematology, and Biostatistics, King's College Hospital, London, United Kingdom. 

OBJECTIVE To evaluate the impact of spleen weight on operative and clinical outcome in a series of 108 consecutive laparoscopic splenectomies.
BACKGROUND Laparoscopic splenectomy as an alternative to open splenectomy for splenomegaly is regarded as controversial.
METHODS Patients underwent laparoscopic splenectomy for a range of hematological disorders between November 1992 and February 2000. Multiple linear and logistic regression analysis were used to assess the effect of massive splenomegaly (>1000 g) on perioperative mortality and morbidity, after adjusting for the joint effects of patient age, weight, pre- and postoperative full blood counts, operating time, estimated blood loss, conversion rate, reoperation rate, and duration of hospital stay.
RESULTS Massive splenomegaly was recorded in 27 of 108 (25%) cases. In this group, splenic weight ranged from 1000 to 4750 g (median, 2500 g). Patients with splenic weight >1000 g had a significantly longer median operating time (170 vs. 102 minutes, P < 0.01), conversion rate (5/27 vs. 4/81, P < 0.05), postoperative morbidity (15/27 vs. 4/81, P < 0.01), and median postoperative stay (5 vs. 3 days, P < 0.01). Multivariate analysis found splenic weight to be the most powerful predictor of morbidity (P < 0.01). Patients with splenomegaly (>1000 g) were 14 times likely to have post operative complications. One patient died 3 days after surgery, following a pulmonary embolus (spleen weight 500 g, mortality 1/108, 0.9%).
CONCLUSIONS Laparoscopic splenectomy is feasible in patients with giant spleens. However, it is associated with greater morbidity, and the advantages of minimal access surgery in this subgroup of patients are not so clear. 

PMID: 12894017




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